From Wikipedia, the free encyclopedia
Jump to navigationJump to search

El tratamiento del VIH / SIDA normalmente incluye el uso de múltiples fármacos antirretrovirales en un intento por controlar la infección por el VIH . Hay varias clases de agentes antirretrovirales que actúan en diferentes etapas del ciclo de vida del VIH . El uso de múltiples fármacos que actúan sobre diferentes dianas virales se conoce como terapia antirretroviral de gran actividad ( TARGA ). HAART disminuye la carga total de VIH del paciente, mantiene la función del sistema inmunológico y previene las infecciones oportunistas que a menudo conducen a la muerte. [1] HAART también previene la transmisión del VIH entre serodiscordantesparejas del mismo sexo y del sexo opuesto, siempre que la pareja VIH positiva mantenga una carga viral indetectable. [2]

El tratamiento ha tenido tanto éxito que en muchas partes del mundo, el VIH se ha convertido en una enfermedad crónica en la que la progresión al SIDA es cada vez más rara. Anthony Fauci , director del Instituto Nacional de Alergias y Enfermedades Infecciosas de los Estados Unidos , ha escrito: "Con una acción colectiva y decidida ahora y un compromiso inquebrantable en los años venideros, una generación libre de SIDA está realmente al alcance". En el mismo documento, señaló que solo en 2010 se salvaron unas 700.000 vidas gracias a la terapia antirretroviral. [3] Como otro comentario en The Lancetseñaló, "En lugar de lidiar con complicaciones agudas y potencialmente mortales, los médicos ahora se enfrentan con el manejo de una enfermedad crónica que, en ausencia de una cura, persistirá durante muchas décadas". [4]

El Departamento de Salud y Servicios Humanos de los Estados Unidos y la Organización Mundial de la Salud [5] recomiendan ofrecer tratamiento antirretroviral a todos los pacientes con VIH . [6] Debido a la complejidad de seleccionar y seguir un régimen, el potencial de efectos secundarios y la importancia de tomar medicamentos con regularidad para prevenir la resistencia viral , tales organizaciones enfatizan la importancia de involucrar a los pacientes en las opciones de terapia y recomiendan analizar los riesgos y la beneficios potenciales. [6]

La Organización Mundial de la Salud ha definido la salud como algo más que la ausencia de enfermedad. Por esta razón, muchos investigadores han dedicado su trabajo a comprender mejor los efectos del estigma relacionado con el VIH, las barreras que crea para las intervenciones de tratamiento y las formas en que se pueden sortear esas barreras. [7] [8]

Clases de medicación

Descripción esquemática del mecanismo de las cuatro clases de medicamentos antirretrovirales disponibles contra el VIH

Hay seis clases de medicamentos, que generalmente se usan en combinación, para tratar la infección por VIH. Los fármacos antirretrovirales (ARV) se clasifican en términos generales por la fase del ciclo de vida del retrovirus que inhibe el fármaco. Las combinaciones típicas incluyen dos inhibidores nucleósidos de la transcriptasa inversa (NRTI) como "columna vertebral" junto con un inhibidor no nucleósido de la transcriptasa inversa (NNRTI), un inhibidor de la proteasa (IP) o inhibidores de la integrasa (también conocidos como inhibidores de la transferencia de la cadena nuclear integrasa o INSTI) ) como "base". [6]

La cloroquina , un ionóforo de zinc , muestra actividad antiviral contra el VIH y reduce la activación inmunitaria. [9] [10] [11] [12]

Inhibidores de entrada

Los inhibidores de entrada (o inhibidores de fusión) interfieren con la unión, fusión y entrada del VIH-1 a la célula huésped al bloquear uno de varios objetivos. Maraviroc y enfuvirtida son los dos agentes disponibles en esta clase. Maraviroc actúa dirigiéndose a CCR5 , un correceptor ubicado en las células T colaboradoras humanas. Sin embargo, se debe tener precaución al administrar este medicamento debido a un posible cambio en el tropismo que permite que el VIH se dirija a un correceptor alternativo como CXCR4 . [ cita requerida ]

En casos raros, los individuos pueden tener una mutación en el gen delta CCR5 que da como resultado un correceptor CCR5 no funcional y, a su vez, un medio de resistencia o progresión lenta de la enfermedad. Sin embargo, como se mencionó anteriormente, esto se puede superar si una variante del VIH que se dirige a CXCR4 se vuelve dominante. [13] Para prevenir la fusión del virus con la membrana del huésped, se puede usar enfuvirtida. La enfuvirtida es un fármaco peptídico que debe inyectarse y actúa interactuando con la repetición heptada N-terminal de la gp41 del VIH para formar un paquete inactivo de hetero seis hélices, evitando así la infección de las células huésped. [14]

Inhibidores nucleósidos / nucleótidos de la transcriptasa inversa

Inhibidores nucleósidos de la transcriptasa inversa (NRTI) y los inhibidores de la transcriptasa inversa nucleótido (NtRTI) son nucleósidos y nucleótidos análogos que inhiben la transcripción inversa. El VIH es un virus de ARN, por lo que no puede integrarse en el ADN del núcleo de la célula humana a menos que primero se transcriba "en sentido inverso" en ADN. Dado que la conversión de ARN en ADN no se realiza de forma natural en la célula de mamífero, la realiza una proteína viral, la transcriptasa inversa , que la convierte en un objetivo selectivo para la inhibición. Los NRTI son terminadores de cadena. Una vez que los NRTI se incorporan a la cadena de ADN, su falta de un grupo 3 'OH impide la incorporación posterior de otros nucleósidos. Tanto los NRTI como los NtRTI actúan comoinhibidores de sustrato competitivos . Los ejemplos de NRTI incluyen zidovudina , abacavir , lamivudina , emtricitabina y de NtRTI: tenofovir y adefovir . [15]

Inhibidores de la transcriptasa inversa no nucleósidos

Los inhibidores de la transcriptasa inversa no nucleósidos (NNRTI) inhiben la transcriptasa inversa al unirse a un sitio alostérico de la enzima; Los NNRTI actúan como inhibidores no competitivos de la transcriptasa inversa . Los NNRTI afectan la manipulación del sustrato (nucleótidos) por la transcriptasa inversa al unirse cerca del sitio activo. Los NNRTI pueden clasificarse además en NNRTI de primera y segunda generación. Los NNRTI de primera generación incluyen nevirapina y efavirenz . Los NNRTI de segunda generación son etravirina y rilpivirina . [15] El VIH-2 es naturalmente resistente a los NNRTI. [dieciséis]

Inhibidores de la integrasa

Los inhibidores de la integrasa (también conocidos como inhibidores de la transferencia de la cadena nuclear de la integrasa o INSTI) inhiben la enzima viral integrasa , que es responsable de la integración del ADN viral en el ADN de la célula infectada. Hay varios inhibidores de la integrasa en ensayo clínico, [ ¿cuándo? ] y raltegravir se convirtió en el primero en recibir la aprobación de la FDA en octubre de 2007. Raltegravir tiene dos grupos de unión a metales que compiten por el sustrato con dos iones Mg 2+ en el sitio de unión a metales de la integrasa. A principios de 2014, otros dos inhibidores de la integrasa aprobados clínicamente son elvitegravir y dolutegravir . [17]

Inhibidores de proteasa

Los inhibidores de proteasa bloquean la enzima proteasa viral necesaria para producir viriones maduros tras la gemación de la membrana del huésped. En particular, estos fármacos previenen la escisión de las proteínas precursoras gag y gag / pol. [18] Las partículas de virus producidas en presencia de inhibidores de proteasa son defectuosas y en su mayoría no infecciosas. Ejemplos de inhibidores de la proteasa del VIH son lopinavir , indinavir , nelfinavir , amprenavir y ritonavir . Se recomiendan darunavir y atazanavir como opciones de terapia de primera línea. [6] Inhibidores de la maduracióntienen un efecto similar al unirse a gag, pero el desarrollo de dos fármacos experimentales de esta clase, bevirimat y vivecon , se detuvo en 2010. [19] La resistencia a algunos inhibidores de la proteasa es alta. Se han desarrollado fármacos de segunda generación que son eficaces contra variantes del VIH que de otro modo serían resistentes. [18]

Terapia de combinación

El ciclo de vida del VIH puede ser tan corto como aproximadamente 1,5 días desde la entrada del virus en una célula, pasando por la replicación, el ensamblaje y la liberación de virus adicionales, hasta la infección de otras células. [20] El VIH carece de enzimas de corrección de pruebas para corregir los errores cometidos cuando convierte su ARN en ADN a través de la transcripción inversa . Su ciclo de vida corto y su alta tasa de error hacen que el virus mute muy rápidamente, lo que resulta en una alta variabilidad genética. La mayoría de las mutaciones son inferiores al virus original (a menudo carecen de la capacidad de reproducirse) o no transmiten ninguna ventaja, pero algunas de ellas tienen una selección natural.superioridad sobre sus padres y puede permitirles esquivar defensas como el sistema inmunológico humano y los medicamentos antirretrovirales. Cuantas más copias activas del virus, mayor será la posibilidad de que se produzca una resistente a los medicamentos antirretrovirales. [21]

Cuando los medicamentos antirretrovirales se usan de manera inadecuada, las cepas resistentes a múltiples medicamentos pueden convertirse en genotipos dominantes muy rápidamente. En la era anterior a la disponibilidad de múltiples clases de fármacos (antes de 1997), los inhibidores de la transcriptasa inversa zidovudina , didanosina , zalcitabina , estavudina y lamivudina se usaban en serie o en combinación, lo que conducía al desarrollo de mutaciones resistentes a múltiples fármacos. [22]

Por el contrario, la terapia de combinación antirretroviral defiende contra la resistencia creando múltiples obstáculos para la replicación del VIH. Esto mantiene bajo el número de copias virales y reduce la posibilidad de una mutación superior. [21] Si surge una mutación que transmite resistencia a uno de los fármacos, los otros fármacos continúan suprimiendo la reproducción de esa mutación. Con raras excepciones, no se ha demostrado que ningún fármaco antirretroviral individual suprima una infección por VIH durante mucho tiempo; estos agentes deben tomarse en combinaciones para que tengan un efecto duradero. Como resultado, el estándar de atención es usar combinaciones de medicamentos antirretrovirales. [6] Las combinaciones generalmente consisten en tres medicamentos de al menos dos clases diferentes. [6]Esta combinación de tres fármacos se conoce comúnmente como cóctel triple. [23] Las combinaciones de antirretrovirales están sujetas a sinergias positivas y negativas , lo que limita el número de combinaciones útiles. [ cita requerida ]

Debido a la tendencia del VIH a mutar, cuando los pacientes que han comenzado un régimen antirretrovial no lo toman con regularidad, se puede desarrollar resistencia. [24] Por otro lado, los pacientes que toman sus medicamentos con regularidad pueden permanecer en un régimen sin desarrollar resistencia. [24] Esto aumenta enormemente la esperanza de vida y deja más medicamentos disponibles para el individuo en caso de que surja la necesidad. [ cita requerida ]

A 2016 advertisement from NIAID promoting the advancement of single-pill antiretrovial drug combinations

In recent years,[when?] drug companies have worked together to combine these complex regimens into single-pill fixed-dose combinations.[25] More than 20 antiretroviral fixed-dose combinations have been developed. This greatly increases the ease with which they can be taken, which in turn increases the consistency with which medication is taken (adherence),[26] and thus their effectiveness over the long-term.

Adjunct treatment

Aunque la terapia antirretroviral ha ayudado a mejorar la calidad de vida de las personas que viven con el VIH, todavía es necesario explorar otras formas de abordar aún más la carga de la enfermedad. Una de esas estrategias potenciales que se investigó fue agregar interleucina 2 como complemento de la terapia antirretroviral para adultos con VIH. Una revisión Cochrane incluyó 25 ensayos controlados aleatorios que se realizaron en seis países. [27] Los investigadores encontraron que la interleucina 2 aumenta el CD4células inmunes, pero no hace una diferencia en términos de muerte e incidencia de otras infecciones. Además, probablemente haya un aumento de los efectos secundarios con la interleucina 2. Los hallazgos de esta revisión no apoyan el uso de la interleucina 2 como tratamiento complementario al tratamiento antirretroviral para adultos con VIH. [ cita requerida ]

Pautas de tratamiento

Inicio de la terapia antirretroviral

Las pautas de tratamiento con medicamentos antirretrovirales han cambiado con el tiempo. Antes de 1987, no se disponía de fármacos antirretrovirales y el tratamiento consistía en tratar las complicaciones de las infecciones oportunistas y las neoplasias. Después de que se introdujeron los medicamentos antirretrovirales, la mayoría de los médicos estuvieron de acuerdo en que los pacientes VIH positivos con recuentos bajos de CD4 deberían ser tratados, pero no se llegó a un consenso sobre si tratar a los pacientes con recuentos altos de CD4. [28]

En abril de 1995, Merck y el Instituto Nacional de Alergias y Enfermedades Infecciosas comenzaron a reclutar pacientes para un ensayo que examinaba los efectos de una combinación de tres fármacos del inhibidor de proteasa indinavir y dos análogos de nucleósidos. [29] que ilustra el beneficio sustancial de combinar 2 NRTI con una nueva clase de antirretrovirales, inhibidores de la proteasa , a saber, indinavir . Más tarde, ese mismo año, David Ho se convirtió en un defensor de este enfoque de "golpe duro, golpe temprano" con un tratamiento agresivo con múltiples antirretrovirales al principio del curso de la infección. [30] Revisiones posteriores de finales de los 90 y principios de los 2000 señalaron que este enfoque de "golpear fuerte, golpear temprano" corría riesgos significativos de aumentar los efectos secundarios y desarrollar resistencia a múltiples fármacos, y este enfoque se abandonó en gran medida. El único consenso fue sobre el tratamiento de pacientes con inmunosupresión avanzada (recuentos de CD4 inferiores a 350 / μL). [31] El tratamiento con antirretrovirales era caro en ese momento, oscilando entre $ 10,000 y $ 15,000 al año. [32]

El momento de comenzar la terapia ha seguido siendo una controversia central dentro de la comunidad médica, aunque reciente [ ¿cuándo? ] los estudios han dado lugar a una mayor claridad. El estudio NA-ACCORD [33] observó a pacientes que iniciaron la terapia antirretroviral con un recuento de CD4 inferior a 500 frente a menos de 350 y mostró que los pacientes que iniciaron el TARV con recuentos de CD4 más bajos tenían un aumento del 69% en el riesgo de muerte. [33] En 2015, los estudios START [34] y TEMPRANO [35] mostraron que los pacientes vivían más tiempo si comenzaban a tomar antirretrovirales en el momento del diagnóstico, en lugar de esperar a que sus recuentos de CD4 descendieran a un nivel específico.

Otros argumentos para comenzar la terapia antes son que se ha demostrado que las personas que comienzan la terapia más tarde tienen menos recuperación de su sistema inmunológico, [36] y los recuentos más altos de CD4 se asocian con menos cáncer. [37]

La Agencia Europea de Medicamentos (EMA) ha recomendado la concesión de autorizaciones de comercialización para dos nuevos medicamentos antirretrovirales (ARV), rilpivirina (Rekambys) y cabotegravir (Vocabria), para su uso conjunto en el tratamiento de personas con el virus de la inmunodeficiencia humana tipo 1 (VIH). -1) infección. [38] Los dos medicamentos son los primeros ARV que vienen en una formulación inyectable de acción prolongada. [38] Esto significa que en lugar de píldoras diarias, las personas reciben inyecciones intramusculares mensualmente o cada dos meses. [38]

La combinación de Rekambys y Vocabria inyectable está destinada al tratamiento de mantenimiento de adultos que tienen niveles indetectables de VIH en sangre (carga viral inferior a 50 copias / ml) con su tratamiento ARV actual, y cuando el virus no ha desarrollado resistencia a cierta clase de medicamentos contra el VIH llamados inhibidores de la transcriptasa inversa no nucleósidos (INNTI) e inhibidores de la transferencia de la cadena de integrasa (INI). [38]

Tratamiento como prevención

Un argumento separado para iniciar la terapia antirretroviral que ha ganado más prominencia es su efecto sobre la transmisión del VIH. El TAR reduce la cantidad de virus en la sangre y las secreciones genitales. [39] [40] Se ha demostrado que esto conduce a una reducción drástica de la transmisión del VIH cuando una pareja con una carga viral suprimida (<50 copias / ml) tiene relaciones sexuales con una pareja que es VIH negativa. En el ensayo clínico HPTN 052 , 1763 serodiscordanteSe planificó el seguimiento de parejas heterosexuales en 9 países durante al menos 10 años, y ambos grupos recibieron educación sobre la prevención de la transmisión del VIH y los condones, pero solo un grupo recibió TAR. El estudio se detuvo antes de tiempo (después de 1,7 años) por razones éticas cuando quedó claro que el tratamiento antivírico proporcionaba una protección significativa. De las 28 parejas en las que se había producido una infección cruzada, todas menos una habían tenido lugar en el grupo de control, lo que concuerda con una reducción del 96% en el riesgo de transmisión mientras recibían TAR. La transmisión única en el grupo experimental se produjo poco después de comenzar el TAR, antes de que fuera probable que se suprimiera la carga viral. [41]La profilaxis previa a la exposición (PrEP, por sus siglas en inglés) proporciona medicamentos a las personas VIH negativas, junto con educación sobre sexo seguro y exámenes de detección de VIH / ITS regulares, para reducir el riesgo de contraer el VIH. [42] En 2011, la revista Science otorgó el premio Avance del año al tratamiento como prevención. [43]

En julio de 2016 se creó un documento de consenso de la Campaña de Acceso a la Prevención que ha sido respaldado por más de 400 organizaciones en 58 países. El documento de consenso establece que el riesgo de transmisión del VIH de una persona que vive con el VIH y que ha sido indetectable durante un mínimo de 6 meses es insignificante o inexistente, siendo insignificante definido como 'tan pequeño o sin importancia que no vale la pena considerarlo'. La presidenta de la Asociación Británica del VIH (BHIVA), Chloe Orkin , declaró en julio de 2017 que `` no debe haber ninguna duda sobre el mensaje claro y simple de que una persona con niveles sostenidos e indetectables del virus del VIH en la sangre no puede transmitir el VIH a su parejas sexuales. [44]

Además, el estudio PARTNER, [45] que se llevó a cabo entre 2010 y 2014, inscribió a 1166 parejas serodiscordantes (donde una pareja es VIH positiva y la otra negativa) en un estudio que encontró que la tasa estimada de transmisión a través de cualquier relación sexual sin condón con el La pareja VIH positiva que toma TAR con una carga de VIH inferior a 200 copias / ml fue cero. [45]

En resumen, como establecen las pautas de tratamiento del VIH de la OMS, "Los regímenes ARV ahora disponibles, incluso en los países más pobres, son más seguros, más simples, más efectivos y más asequibles que nunca". [46]

Existe un consenso entre los expertos de que, una vez iniciada, la terapia antirretroviral nunca debe interrumpirse. Esto se debe a que la presión de selección de la supresión incompleta de la replicación viral en presencia de farmacoterapia provoca la inhibición selectiva de las cepas más sensibles al fármaco. Esto permite que las cepas resistentes a los medicamentos se vuelvan dominantes. Esto, a su vez, dificulta el tratamiento de la persona infectada y de cualquier otra persona a la que infecte. [6] Un ensayo mostró tasas más altas de infecciones oportunistas, cánceres, ataques cardíacos y muerte en pacientes que interrumpieron periódicamente su TAR. [47] [48]

Fuentes de la guía

Existen varias pautas de tratamiento para adultos infectados por el VIH-1 en el mundo desarrollado (es decir, aquellos países con acceso a todas o la mayoría de las terapias y pruebas de laboratorio). En los Estados Unidos existe tanto la International AIDS Society-USA (IAS-USA) (una organización sin fines de lucro 501 (c) (3) en los EE. UU.) [49] así como el Departamento de Salud del gobierno de EE. UU. Y Pautas de servicios humanos . [6] En Europa existen las directrices de la Sociedad Clínica Europea del SIDA. [50]

Para países con recursos limitados, la mayoría de las pautas nacionales siguen de cerca las pautas de la Organización Mundial de la Salud . [5]

Directrices

Las pautas utilizan nuevos criterios para considerar el inicio de TARGA, como se describe a continuación. Sin embargo, sigue habiendo una variedad de opiniones sobre este tema y la decisión de comenzar el tratamiento en última instancia recae en el paciente y su médico. [ cita requerida ]

Las pautas del DHHS de EE. UU. (Publicadas el 8 de abril de 2015) establecen:

  • Se recomienda la terapia antirretroviral (TAR) para todas las personas infectadas por el VIH para reducir el riesgo de progresión de la enfermedad.
  • El TAR también se recomienda para las personas infectadas por el VIH para la prevención de la transmisión del VIH.
  • Los pacientes que comienzan el TAR deben estar dispuestos y ser capaces de comprometerse con el tratamiento y comprender los beneficios y riesgos de la terapia y la importancia de la adherencia. Los pacientes pueden optar por posponer la terapia y los proveedores, caso por caso, pueden optar por posponer la terapia en función de factores clínicos y / o psicosociales.

Las pautas más recientes de la Organización Mundial de la Salud (con fecha del 30 de septiembre de 2015) ahora concuerdan y establecen: [5]

  • La terapia antirretroviral (TAR) debe iniciarse en todas las personas que viven con el VIH con cualquier recuento de células CD4.

Resistencia inicial

La resistencia inicial es la presencia de mutaciones de resistencia en pacientes que nunca antes han sido tratados contra el VIH. En países con una alta tasa de resistencia inicial, se recomienda realizar pruebas de resistencia antes de iniciar el tratamiento; o, si el inicio del tratamiento es urgente, entonces debe iniciarse un régimen de tratamiento de "mejor estimación", que luego se modifica sobre la base de las pruebas de resistencia. [16] En el Reino Unido, existe un 11,8% de resistencia de nivel medio a alto al inicio del estudio a la combinación de efavirenz + zidovudina + lamivudina, y un 6,4% de resistencia de nivel medio a alto a estavudina + lamivudina + nevirapina . [51] En los EE. UU., El 10,8% de una cohorte de pacientes que nunca antes habían recibido TAR tenían al menos una mutación de resistencia en 2005.[52] Varias encuestas en diferentes partes del mundo han mostrado tasas crecientes o estables de resistencia inicial a medida que avanza la era de la terapia eficaz contra el VIH. [53] [54] [55] [56] Con la prueba de resistencia inicial, se puede personalizar una combinación de antirretrovirales que probablemente sean efectivos para cada paciente. [ cita requerida ]

Regímenes

La mayoría de los regímenes HAART constan de tres medicamentos: 2 NRTI ("columna vertebral") + un PI / NNRTI / INSTI ("base"). Los regímenes iniciales utilizan fármacos de "primera línea" con una alta eficacia y un perfil bajo de efectos secundarios.

Los regímenes iniciales preferidos por el DHHS de EE. UU. Para adultos y adolescentes en los Estados Unidos, en abril de 2015, son: [6]

  • tenofovir / emtricitabina y raltegravir (un inhibidor de la integrasa )
  • tenofovir / emtricitabina y dolutegravir (un inhibidor de la integrasa)
  • abacavir / lamivudina (dos NRTI) y dolutegravir para pacientes que han resultado negativos para el alelo del gen HLA-B * 5701
  • tenofovir / emtricitabina, elvitegravir (un inhibidor de la integrasa) y cobicistat (que inhibe el metabolismo del primero) en pacientes con buena función renal ( gfr > 70)
  • tenofovir / emtricitabina, ritonavir y darunavir (ambos últimos son inhibidores de la proteasa )

Tanto efavirenz como nevirapina mostraron beneficios similares cuando se combinaron con NRTI respectivamente. [57]

En el caso de los regímenes basados ​​en inhibidores de proteasa, el ritonavir se usa en dosis bajas para inhibir las enzimas del citocromo p450 y "aumentar" los niveles de otros inhibidores de proteasa, en lugar de por su efecto antivírico directo. Este efecto estimulante permite que se tomen con menos frecuencia durante el día. [58] Cobicistat se usa con elvitegravir para obtener un efecto similar, pero no tiene ningún efecto antivírico directo en sí mismo. [59]

El régimen inicial preferido por la OMS para adultos y adolescentes al 30 de junio de 2013 es: [46]

  • tenofovir + lamivudina (o emtricitabina) + efavirenz

Poblaciones especiales

Infección aguda

En los primeros seis meses después de la infección, la carga viral del VIH tiende a ser elevada y las personas presentan síntomas con más frecuencia que en las últimas fases latentes de la enfermedad por VIH. Puede haber beneficios especiales al comenzar la terapia antirretroviral temprano durante esta fase aguda, incluida la reducción del "punto de ajuste" viral o la carga viral inicial, reducir la tasa de mutación del virus y reducir el tamaño del reservorio viral (consulte la sección siguiente sobre reservorios virales ). [6] El ensayo SPARTAC comparó 48 semanas de TAR versus 12 semanas versus ningún tratamiento en la infección aguda por VIH y encontró que 48 semanas de tratamiento retrasaron el tiempo para disminuir el recuento de CD4 por debajo de 350 células por ml en 65 semanas y mantuvieron las cargas virales significativamente más bajas incluso después de interrumpir el tratamiento. [60]

Dado que las cargas virales suelen ser muy altas durante la infección aguda, este período conlleva un riesgo de transmisión estimado 26 veces mayor. [61] Al tratar a pacientes con infección aguda, se presume que podría tener un impacto significativo en la disminución de las tasas generales de transmisión del VIH, ya que una menor carga viral se asocia con un menor riesgo de transmisión (ver la sección sobre tratamiento como prevención ). Sin embargo, no se ha demostrado un beneficio general y debe equilibrarse con los riesgos del tratamiento del VIH. La terapia durante la infección aguda tiene una recomendación de grado BII del DHHS de EE. UU. [6]

Niños

HIV can be especially harmful to infants and children, with one study in Africa showing that 52% of untreated children born with HIV had died by age 2.[62] By five years old, the risk of disease and death from HIV starts to approach that of young adults. The WHO recommends treating all children less than 5 years old, and starting all children older than 5 with stage 3 or 4 disease or CD4 <500 cells/ml.[46] DHHS guidelines are more complicated but recommend starting all children less than 12 months old and children of any age who have symptoms.[63]

En cuanto a qué antirretrovirales usar, esto se complica por el hecho de que muchos niños que nacen de madres con VIH reciben una dosis única de nevirapina (un INNTI) en el momento del nacimiento para prevenir la transmisión. Si esto falla, puede provocar resistencia a los NNRTI. [64] Además, un estudio grande en África e India encontró que un régimen basado en IP era superior a un régimen basado en NNRTI en niños menores de 3 años que nunca habían estado expuestos a NNRTI en el pasado. [65] Por tanto, la OMS recomienda regímenes basados ​​en IP para niños menores de 3 años.

La OMS recomienda para niños menores de 3 años: [46]

  • abacavir (o zidovudina) + lamivudina + lopinivir + ritonivir

y para niños de 3 años a menos de 10 años y adolescentes <35 kilogramos:

  • abacavir + lamivudina + efavirenz

Las pautas del DHHS de EE. UU. Son similares pero incluyen opciones basadas en IP para niños> 3 años. [63]

Una revisión sistemática evaluó los efectos y la seguridad de los regímenes que contienen abacavir como terapia de primera línea para niños entre 1 mes y 18 años de edad en comparación con los regímenes con otros INTI. [66] Esta revisión incluyó dos ensayos y dos estudios observacionales con casi once mil niños y adolescentes infectados por el VIH. Midieron la supresión virológica, la muerte y los eventos adversos. Los autores encontraron que no existe una diferencia significativa entre los regímenes que contienen abacavir y otros regímenes que contienen NRTI. La evidencia es de calidad baja a moderada y, por lo tanto, es probable que la investigación futura cambie estos hallazgos. [ cita requerida ]

Mujeres embarazadas

Los objetivos del tratamiento para las mujeres embarazadas incluyen los mismos beneficios para la madre que en otros adultos infectados, así como la prevención de la transmisión a su hijo. El riesgo de transmisión de madre a hijo es proporcional a la carga viral plasmática de la madre. Las madres no tratadas con una carga viral> 100.000 copias / ml tienen un riesgo de transmisión superior al 50%. [67] El riesgo cuando la carga viral es <1000 copias / ml es menor al 1%. [68] Se recomienda el TAR para las madres antes y durante el parto y para las madres y los bebés después del parto para reducir sustancialmente el riesgo de transmisión. [69] El modo de parto también es importante, ya que una cesárea planificada tiene un riesgo menor que el parto vaginal o la cesárea de emergencia.[68]

HIV can also be detected in breast milk of infected mothers and transmitted through breast feeding.[70] The WHO balances the low risk of transmission through breast feeding from women who are on ART with the benefits of breastfeeding against diarrhea, pneumonia and malnutrition. It also strongly recommends that breastfeeding infants receive prophylactic ART.[46] In the US, the DHHS recommends against women with HIV breastfeeding.[69]

Older adults

With improvements in HIV therapy, several studies now estimate that patients on treatment in high-income countries can expect a normal life expectancy.[71][72] This means that a higher proportion of people living with HIV are now older and research is ongoing into the unique aspects of HIV infection in the older adult. There is data that older people with HIV have a blunted CD4 response to therapy but are more likely to achieve undetectable viral levels.[73] However, not all studies have seen a difference in response to therapy.[74] The guidelines do not have separate treatment recommendations for older adults, but it is important to take into account that older patients are more likely to be on multiple non-HIV medications and consider drug interactions with any potential HIV medications.[75] There are also increased rates of HIV associated non-AIDS conditions (HANA) such as heart disease, liver disease and dementia that are multifactorial complications from HIV, associated behaviors, coinfections like hepatitis B, hepatitis C, and human papilloma virus (HPV) as well as HIV treatment.[75]

Adults with depression

Many factors may contribute to depression in adults living with HIV, such as the effects of the virus on the brain, other infections or tumours, antiretroviral drugs and other medical treatment.[76] Rates of major depression are higher in people living with HIV compared to the general population, and this may negatively influence antiretroviral treatment. In a systematic review, Cochrane researchers assessed whether giving antidepressants to adults living with both HIV and depression may improve depression.[76] Ten trials, of which eight were done in high-income countries, with 709 participants were included. Results indicated that antidepressants may be better in improving depression compared to placebo, but the quality of the evidence is low and future research is likely to impact on the findings.[citation needed]

Concerns

There are several concerns about antiretroviral regimens that should be addressed before initiating:

  • Intolerance: The drugs can have serious side-effects which can lead to harm as well as keep patients from taking their medications regularly.
  • Resistance: Not taking medication consistently can lead to low blood levels that foster drug resistance.[77]
  • Cost: The WHO maintains a database of world ART costs[78] which have dropped dramatically in recent[when?] years as more first line drugs have gone off-patent.[79] A one pill, once a day combination therapy has been introduced in South Africa for as little as $10 per patient per month.[80] One recent[when?] study estimated an overall cost savings to ART therapy in South Africa given reduced transmission.[81] In the United States, new on-patent regimens can cost up to $28,500 per patient, per year.[82][83]
  • Public health: Individuals who fail to use antiretrovirals as directed can develop multi-drug resistant strains which can be passed onto others.[84]

Response to therapy

Virologic response

Suppressing the viral load to undetectable levels (<50 copies per ml) is the primary goal of ART.[58] This should happen by 24 weeks after starting combination therapy.[85] Viral load monitoring is the most important predictor of response to treatment with ART.[86] Lack of viral load suppression on ART is termed virologic failure. Levels higher than 200 copies per ml is considered virologic failure, and should prompt further testing for potential viral resistance.[6]

Research has shown that people with an undetectable viral load are unable to transmit the virus through condomless sex with a partner of either gender. The 'Swiss Statement' of 2008 described the chance of transmission as 'very low' or 'negligible,'[87] but multiple studies have since shown that this mode of sexual transmission is impossible where the HIV-positive person has a consistently undetectable viral load. This discovery has led to the formation of the Prevention Access Campaign are their 'U=U' or 'Undetectable=Untransmittable' public information strategy,[88][89] an approach that has gained widespread support amongst HIV/AIDS-related medical, charitable, and research organisations.[44] The studies demonstrating that U=U is an effective strategy for preventing HIV transmission in serodiscordant couples so long as "the partner living with HIV [has] a durably suppressed viral load" include:[90] Opposites Attract,[91] PARTNER 1,[45] PARTNER 2,[92][93] (for male-male couples)[90] and HPTN052[94] (for heterosexual couples).[90] In these studies, couples where one partner was HIV-positive and one partner was HIV-negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported, there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetectable viral load.[95] Following this the U=U consensus statement advocating the use of 'zero risk' was signed by hundreds of individuals and organisations including the US CDC, British HIV Association and The Lancet medical journal.[44] The importance of the final results of the PARTNER 2 study were described by the medical director of the Terrence Higgins Trust as "impossible to overstate," while lead author Alison Rodger declared that the message that "undetectable viral load makes HIV untransmittable ... can help end the HIV pandemic by preventing HIV transmission."[96] The authors summarised their findings in The Lancet as follows:[92]

Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.[92]

This result is consistent with the conclusion presented by Anthony S. Fauci, the Director of the National Institute of Allergy and Infectious Diseases for the U.S. National Institutes of Health, and his team in a viewpoint published in the Journal of the American Medical Association, that U=U is an effective HIV prevention method when an undetectable viral load is maintained.[2][90]

Immunologic response

CD4 cell counts are another key measure of immune status and ART effectiveness.[85] CD4 counts should rise 50 to 100 cells per ml in the first year of therapy.[58] There can be substantial fluctuation in CD4 counts of up to 25% based on the time of day or concomitant infections.[97] In one long-term study, the majority of increase in CD4 cell counts was in the first two years after starting ART with little increase afterwards. This study also found that patients who began ART at lower CD4 counts continued to have lower CD4 counts than those who started at higher CD4 counts.[98] When viral suppression on ART is achieved but without a corresponding increase in CD4 counts it can be termed immunologic nonresponse or immunologic failure. While this is predictive of worse outcomes, there is no consensus on how to adjust therapy to immunologic failure and whether switching therapy is beneficial. DHHS guidelines do not recommend switching an otherwise suppressive regimen.[6][99]

Innate lymphoid cells (ILC) are another class of immune cell that is depleted during HIV infection. However, if ART is initiated before this depletion at around 7 days post infection, ILC levels can be maintained. While CD4 cell counts typically replenish after effective ART, ILCs depletion is irreversible with ART initiated after the depletion despite suppression of viremia.[100] Since one of the roles of ILCs is to regulate the immune response to commensal bacteria and to maintain an effective gut barrier,[101] it has been hypothesized that the irreversible depletion of ILCs plays a role in the weakened gut barrier of HIV patients, even after successful ART.[102]

Salvage therapy

In patients who have persistently detectable viral loads while taking ART, tests can be done to investigate whether there is drug resistance. Most commonly a genotype is sequenced which can be compared with databases of other HIV viral genotypes and resistance profiles to predict response to therapy.[103] Resistance testing may improve virological outcomes in those who have treatment failures. However, there is lack of evidence of effectiveness of such testing in those who have not done any treatment before.[104]

If there is extensive resistance a phenotypic test of a patient's virus against a range of drug concentrations can be performed, but is expensive and can take several weeks, so genotypes are generally preferred.[6] Using information from a genotype or phenotype, a regimen of 3 drugs from at least 2 classes is constructed that will have the highest probability of suppressing the virus. If a regimen cannot be constructed from recommended first line agents it is termed salvage therapy, and when 6 or more drugs are needed it is termed mega-HAART.[105]

Structured treatment interruptions

Drug holidays (or "structured treatment interruptions") are intentional discontinuations of antiretroviral drug treatment. As mentioned above, randomized controlled studies of structured treatment interruptions have shown higher rates of opportunistic infections, cancers, heart attacks and death in patients who took drug holidays.[47][48][106] With the exception of post exposure prophylaxis, treatment guidelines do not call for the interruption of drug therapy once it has been initiated.[6][46][85][106]

Adverse effects

Each class and individual antiretroviral carries unique risks of adverse side effects.

NRTIs

The NRTIs can interfere with mitochondrial DNA synthesis and lead to high levels of lactate and lactic acidosis, liver steatosis, peripheral neuropathy, myopathy and lipoatrophy.[58] First-line NRTIs such as lamivudine/emtrictabine, tenofovir, and abacavir are less likely to cause mitochondrial dysfunction.[107][108]

Mitochondrial Haplogroups(mtDNA), non pathologic mutations inherited from the maternal line, have been linked to the efficacy of CD4+ count following ART.[109][110][111][112] Idiosyncratic toxicity with mtDNA haplogroup is also well studied.(Boeisteril et al, 2007).[113]

NNRTIs

NNRTIs are generally safe and well tolerated. The main reason for discontinuation of efavirenz is neuro-psychiatric effects including suicidal ideation. Nevirapine can cause severe hepatotoxicity, especially in women with high CD4 counts.[114]

Protease inhibitors

Protease inhibitors (PIs) are often given with ritonavir, a strong inhibitor of cytochrome P450 enzymes, leading to numerous drug-drug interactions. They are also associated with lipodystrophy, elevated triglycerides and elevated risk of heart attack.[115]

Integrase inhibitors

Integrase inhibitors (INSTIs) are among the best tolerated of the antiretrovirals with excellent short and medium term outcomes. Given their relatively new development there is less long term safety data. They are associated with an increase in creatinine kinase levels and rarely myopathy.[116]

HIV postexposure prophylaxis (PEP)

When people are exposed to HIV-positive infectious bodily fluids either through skin puncture, contact with mucous membranes or contact with damaged skin, they are at risk for acquiring HIV. Pooled estimates give a risk of transmission with puncture exposures of 0.3%[117] and mucous membrane exposures 0.63%.[118] United States guidelines state that "feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody."[119] Given the rare nature of these events, rigorous study of the protective abilities of antiretrovirals are limited but do suggest that taking antiretrovirals afterwards can prevent transmission.[120] It is unknown if three medications are better than two. The sooner after exposure that ART is started the better, but after what period they become ineffective is unknown, with the US Public Health Service Guidelines recommending starting prophylaxis up to a week after exposure.[119] They also recommend treating for a duration of four weeks based on animal studies. Their recommended regimen is emtricitabine + tenofovir + raltegravir (an INSTI). The rationale for this regimen is that it is "tolerable, potent, and conveniently administered, and it has been associated with minimal drug interactions."[119] People who are exposed to HIV should have follow up HIV testing at six, 12, and 24 weeks.[citation needed]

Pregnancy planning

Women with HIV have been shown to have decreased fertility which can affect available reproductive options.[121] In cases where the woman is HIV negative and the man is HIV positive, the primary assisted reproductive method used to prevent HIV transmission is sperm washing followed by intrauterine insemination (IUI) or in vitro fertilization (IVF). Preferably this is done after the man has achieved an undetectable plasma viral load.[122] In the past there have been cases of HIV transmission to an HIV-negative partner through processed artificial insemination,[123] but a large modern series in which followed 741 couples where the man had a stable viral load and semen samples were tested for HIV-1, there were no cases of HIV transmission.[124]

For cases where the woman is HIV positive and the man is HIV negative, the usual method is artificial insemination.[122] With appropriate treatment the risk of mother-to-child infection can be reduced to below 1%.[125]

History

Several buyers clubs sprang up since 1986 to combat HIV. AZT nucleoside reverse-transcriptase inhibitor (NRTI), zidovudine (AZT) was not effective on its own. It was approved by the US FDA in 1987.[126] The FDA bypassed stages of its review for safety and effectiveness in order to distribute this drug earlier.[127] Subsequently, several more NRTIs were developed but even in combination were unable to suppress the virus for long periods of time and patients still inevitably died.[128] To distinguish from this early antiretroviral therapy (ART), the term highly active antiretroviral therapy (HAART) was introduced. In 1996 by sequential publications in The New England Journal of Medicine by Hammer and colleagues[129] and Gulick and colleagues[29] illustrating the substantial benefit of combining 2 NRTIs with a new class of antiretrovirals, protease inhibitors, namely indinavir. This concept of 3-drug therapy was quickly incorporated into clinical practice and rapidly showed impressive benefit with a 60% to 80% decline in rates of AIDS, death, and hospitalization.[1]

As HAART became widespread, fixed dose combinations were made available to ease the administration. Later, the term combination antiretroviral therapy (cART) gained favor with some physicians as a more accurate name, not conveying to patients any misguided idea of the nature of the therapy.[130] Today multidrug, highly effective regimens are long since the default in ART, which is why they are increasingly called simply ART instead of HAART or cART.[130] This retronymic process is linguistically comparable to the way that the words electronic computer and digital computer at first were needed to make useful distinctions in computing technology, but with the later irrelevance of the distinction, computer alone now covers their meaning. Thus as "all computers are digital now", so "all ART is combination ART now." However, the names HAART and cART, reinforced by thousands of earlier mentions in medical literature still being regularly cited, also remain in use.[citation needed]

Research

People living with HIV can expect to live a nearly normal life span if able to achieve durable viral suppression on combination antiretroviral therapy. However this requires lifelong medication and will still have higher rates of cardiovascular, kidney, liver and neurologic disease.[131] This has prompted further research towards a cure for HIV.

Patients cured of HIV infection

The so-called "Berlin patient" has been potentially cured of HIV infection and has been off of treatment since 2006 with no detectable virus.[132] This was achieved through two bone marrow transplants that replaced his immune system with a donor's that did not have the CCR5 cell surface receptor, which is needed for some variants of HIV to enter a cell.[133] Bone marrow transplants carry their own significant risks including potential death and was only attempted because it was necessary to treat a blood cancer he had. Attempts to replicate this have not been successful and given the risks, expense and rarity of CCR5 negative donors, bone marrow transplant is not seen as a mainstream option.[131] It has inspired research into other methods to try to block CCR5 expression through gene therapy. A procedure zinc-finger nuclease-based gene knockout has been used in a Phase I trial of 12 humans and led to an increase in CD4 count and decrease in their viral load while off antiretroviral treatment.[134] Attempt to reproduce this failed in 2016. Analysis of the failure showed that gene therapy only successfully treats 11-28% of cells, leaving the majority of CD4+ cells capable of being infected. The analysis found that only patients where less than 40% of cells were infected had reduced viral load. The Gene therapy was not effective if the native CD4+ cells remained. This is the main limitation which must be overcome for this treatment to become effective.[135]

After the "Berlin patient", two additional patients with both HIV infection and cancer were reported to have no traceable HIV virus after successful stem cell transplants. Virologist Annemarie Wensing of the University Medical Center Utrecht announced this development during her presentation at the 2016 "Towards an HIV Cure" symposium.[136][137][138] However, these two patients are still on antiretroviral therapy, which is not the case for the Berlin patient. Therefore, it is not known whether or not the two patients are cured of HIV infection. The cure might be confirmed if the therapy were to be stopped and no viral rebound occurred.[139]

In March 2019, a second patient, referred to as the "London Patient", was confirmed to be in complete remission of HIV. Like the Berlin Patient, the London Patient received a bone marrow transplant from a donor who has the same CCR5 mutation. He has been off antiviral drugs since September 2017, indicating the Berlin Patient was not a "one-off".[140][141]

Viral reservoirs

The main obstacle to complete elimination of HIV infection by conventional antiretroviral therapy is that HIV is able to integrate itself into the DNA of host cells and rest in a latent state, while antiretrovirals only attack actively replicating HIV. The cells in which HIV lies dormant are called the viral reservoir, and one of the main sources is thought to be central memory and transitional memory CD4+ T cells.[142] In 2014 there were reports of the cure of HIV in two infants,[143] presumably due to the fact that treatment was initiated within hours of infection, preventing HIV from establishing a deep reservoir.[144] There is work being done[when?] to try to activate reservoir cells into replication so that the virus is forced out of latency and can be attacked by antiretrovirals and the host immune system. Targets include histone deacetylase (HDAC) which represses transcription and if inhibited can lead to increased cell activation. The HDAC inhibitors valproic acid and vorinostat have been used in human trials with only preliminary results so far.[145][146]

Immune activation

Even with all latent virus deactivated, it is thought that a vigorous immune response will need to be induced to clear all the remaining infected cells.[131] Strategies include using cytokines to restore CD4+ cell counts as well as therapeutic vaccines to prime immune responses.[147] One such candidate vaccine is Tat Oyi, developed by Biosantech.[148] This vaccine is based on the HIV protein tat. Animal models have shown the generation of neutralizing antibodies and lower levels of HIV viremia.[149]

Drug advertisements

Direct-to-consumer and other advertisements for HIV drugs in the past were criticized for their use of healthy, glamorous models rather than typical people with HIV/AIDS. Usually, these people will present with debilitating conditions or illnesses as a result of HIV/AIDS. In contrast, by featuring people in unrealistically strenuous activities, such as mountain climbing,[150] this proved to be offensive and insensitive to the suffering of people who are HIV positive. The US FDA reprimanded multiple pharmaceutical manufacturers for publishing such adverts in 2001, as the misleading advertisements harmed consumers by implying unproven benefits and failing to disclose important information about the drugs.[151]Overall, some drug companies chose not to present their drugs in a realistic way, which consequently harmed the general public's ideas[citation needed], suggesting that HIV would not affect you as much as suggested. This led to people not wanting to get tested[citation needed], for fear of being HIV positive, because at the time (in the 80s and 90s particularly), having contracted HIV was seen as a death sentence, as there was no known cure. An example of such a case is Freddie Mercury[citation needed], who died in 1991, aged 45, of AIDS-related Pneumonia.

Beyond medical management

The preamble to the World Health Organization's Constitution defines health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity."[152] Those living with HIV today are met with other challenges that go beyond the singular goal of lowering their viral load. A 2009 meta-analysis studying the correlates of HIV-stigma found that individuals living with higher stigma burden were more likely to have poorer physical and mental health.[8] Insufficient social support and delayed diagnosis due to decreased frequency of HIV testing and knowledge of risk reduction were cited as some of the reasons.[8][153][7][154][155] People living with HIV (PLHIV) have lower health related quality of life (HRQoL) scores than do the general population.[154][153] The stigma of having HIV is often compounded with the stigma of identifying with the LGBTQ community or the stigma of being an injecting drug user (IDU) even though heterosexual sexual transmission accounts for 85% of all HIV-1 infections worldwide.[156][106] AIDS has been cited as the most heavily stigmatized medical condition among infectious diseases.[155] Part of the consequence of this stigma toward PLHIV is the belief that they are seen as responsible for their status and less deserving of treatment.[156][8]

A 2016 study sharing the WHO's definition of health critiques its 90-90-90 target goal, which is part of a larger strategy that aims to eliminate the AIDS epidemic as a public health threat by 2030, by arguing that it does not go far enough in ensuring the holistic health of PLHIV.[7] The study suggests that maintenance of HIV and AIDS should go beyond the suppression of viral load and the prevention of opportunistic infection. It proposes adding a 'fourth 90' addressing a new 'quality of life' target that would focus specifically on increasing the quality of life for those that are able to suppress their viral load to undetectable levels along with new metrics to track the progress toward that target.[7] This study serves as an example of the shifting paradigm in the dynamics of the health care system from being heavily 'disease-oriented' to more 'human-centered'. Though questions remain of what exactly a more 'human-centered' method of treatment looks like in practice, it generally aims to ask what kind of support, other than medical support, PLHIV need to cope with and eliminate HIV-related stigmas.[8][7] Campaigns and marketing aimed at educating the general public in order to reduce any misplaced fears of HIV contraction is one example.[8] Also encouraged is the capacity-building and guided development of PLHIV into more leadership roles with the goal of having a greater representation of this population in decision making positions.[8] Structural legal intervention has also been proposed, specifically referring to legal interventions to put in place protections against discrimination and improve access to employment opportunities.[8] On the side of the practitioner, greater competence for the experience of people living with HIV is encouraged alongside the promotion of an environment of nonjudgment and confidentiality.[8]

Psychosocial group interventions such as psychotherapy, relaxation, group support, and education may have some beneficial effects on depression in HIV positive people.[157]

Food insecurity

The successful treatment and management of HIV/AIDS is affected by a plethora of factors which ranges from successfully taking prescribed medications, preventing opportunistic infection, and food access etc. Food insecurity is a condition in which households lack access to adequate food because of limited money or other resources. Food insecurity is a global issue that have affect billions of people yearly including those living in developed countries.

Food insecurity is a major public health disparity in the United States of America, which significantly affects minority groups, people living at or below the poverty line, and those who are living with one or more morbidity. As of December 31, 2017, there were approximately 126,742 people living with HIV/AIDS (PLWHA) in NYC, of which 87.6% can be described as living with some level of poverty and food insecurity as reported by the NYC Department of Health March 31st, 2019.[158] Having access to a consistent food supply that is safe and healthy is an important part in the treatment and management of HIV/AIDS. PLWHA are also greatly affected by food inequities and food deserts which causes them to be food insecure. Food insecurity, which can cause malnutrition, can also negatively impact HIV treatment and recovery from opportunistic infections. Similarly, PLWHA require additional calories and nutritionally support that require foods free from contamination to prevent further immunocompromising. Food insecurity can further exacerbate the progression of HIV/AIDS and can prevent PLWHA from consistently following their prescribed regimen, which will lead to poor outcomes.

It is imperative that these food insecurity among PLWHA are addressed and rectified to reduce this health inequity.[159][circular reference] It is important to recognized that socioeconomic status, access to medical care, geographic location, public policy, race and ethnicity all play a pivotal role in the treatment and management of HIV/AIDS. The lack of sufficient and constant income does limit the options for food, treatment, and medications. The same can be inferred for those who are among the oppressed groups in society who are marginalized and may be less inclined or encouraged to seek care and assistance. Endeavors to address food insecurity should be included in HIV-treatment programs and may help improve health outcomes if it also focuses on health equity among the diagnosed as much as it focuses on medications. Access to consistently safe and nutritious foods is one of the most important facets in ensuring PLWHA are being provided the best possible care. By altering the narratives for HIV treatment so that more support can be garnered to reduce food insecurity and other health disparities mortality rates will decrease for people living with HIV/AIDS.

See also

  • Antiviral drug
  • AV-HALT
  • Discovery and development of HIV-protease inhibitors
  • Discovery and development of non-nucleoside reverse-transcriptase inhibitors
  • Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors

References

  1. ^ a b Moore RD, Chaisson RE (October 1999). "Natural history of HIV infection in the era of combination antiretroviral therapy". AIDS. 13 (14): 1933–42. doi:10.1097/00002030-199910010-00017. PMID 10513653.
  2. ^ a b Eisinger RW, Dieffenbach CW, Fauci AS (February 2019). "HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable". JAMA. 321 (5): 451–452. doi:10.1001/jama.2018.21167. PMID 30629090. S2CID 58599661.
  3. ^ Fauci AS, Folkers GK (July 2012). "Toward an AIDS-free generation". JAMA. 308 (4): 343–4. doi:10.1001/jama.2012.8142. PMID 22820783.
  4. ^ Deeks SG, Lewin SR, Havlir DV (November 2013). "The end of AIDS: HIV infection as a chronic disease". Lancet. 382 (9903): 1525–33. doi:10.1016/S0140-6736(13)61809-7. PMC 4058441. PMID 24152939.
  5. ^ a b c "Guidelines: HIV". World Health Organization. Retrieved 2015-10-27.
  6. ^ a b c d e f g h i j k l m n o "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" (PDF). US Department of Health and Human Services. 2015-04-08. Cite journal requires |journal= (help)
  7. ^ a b c d e Lazarus JV, Safreed-Harmon K, Barton SE, Costagliola D, Dedes N, Del Amo Valero J, et al. (June 2016). "Beyond viral suppression of HIV - the new quality of life frontier". BMC Medicine. 14 (1): 94. doi:10.1186/s12916-016-0640-4. PMC 4916540. PMID 27334606.
  8. ^ a b c d e f g h i Logie C, Gadalla TM (June 2009). "Meta-analysis of health and demographic correlates of stigma towards people living with HIV". AIDS Care. 21 (6): 742–53. doi:10.1080/09540120802511877. PMID 19806490. S2CID 29881807.
  9. ^ Tsai WP, Nara PL, Kung HF, Oroszlan S (April 1990). "Inhibition of human immunodeficiency virus infectivity by chloroquine". AIDS Research and Human Retroviruses. 6 (4): 481–9. doi:10.1089/aid.1990.6.481. PMID 1692728.
  10. ^ Romanelli F, Smith KM, Hoven AD (1 August 2004). "Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity". Current Pharmaceutical Design. 10 (21): 2643–8. doi:10.2174/1381612043383791. PMID 15320751.
  11. ^ Murray SM, Down CM, Boulware DR, Stauffer WM, Cavert WP, Schacker TW, et al. (November 2010). "Reduction of immune activation with chloroquine therapy during chronic HIV infection". Journal of Virology. 84 (22): 12082–6. doi:10.1128/JVI.01466-10. PMC 2977889. PMID 20844049.
  12. ^ Savarino A, Shytaj IL (June 2015). "Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS". Retrovirology. 12 (1): 51. doi:10.1186/s12977-015-0178-0. PMC 4472405. PMID 26084487.
  13. ^ Lieberman-Blum SS, Fung HB, Bandres JC (July 2008). "Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection". Clinical Therapeutics. 30 (7): 1228–50. doi:10.1016/S0149-2918(08)80048-3. PMID 18691983.
  14. ^ Bai Y, Xue H, Wang K, Cai L, Qiu J, Bi S, et al. (February 2013). "Covalent fusion inhibitors targeting HIV-1 gp41 deep pocket". Amino Acids. 44 (2): 701–13. doi:10.1007/s00726-012-1394-8. PMID 22961335. S2CID 18521851.
  15. ^ a b Das K, Arnold E (April 2013). "HIV-1 reverse transcriptase and antiviral drug resistance. Part 1". Current Opinion in Virology. 3 (2): 111–8. doi:10.1016/j.coviro.2013.03.012. PMC 4097814. PMID 23602471.
  16. ^ a b Geretti, ed. (2006). "9". Antiretroviral Resistance in Clinical Practice. Mediscript. ISBN 978-0-955-16690-7.
  17. ^ Métifiot M, Marchand C, Pommier Y (2013). "HIV integrase inhibitors: 20-year landmark and challenges". Antiviral Agents. Advances in Pharmacology. 67. pp. 75–105. doi:10.1016/B978-0-12-405880-4.00003-2. ISBN 9780124058804. PMC 7569752. PMID 23885999.
  18. ^ a b Wensing AM, van Maarseveen NM, Nijhuis M (January 2010). "Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance". Antiviral Research. 85 (1): 59–74. doi:10.1016/j.antiviral.2009.10.003. PMID 19853627.
  19. ^ "Myriad Genetics suspends its HIV maturation inhibitor program". AIDSmeds. 8 June 2012. Archived from the original on 8 September 2015. Retrieved 27 June 2012.
  20. ^ Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (March 1996). "HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time". Science. 271 (5255): 1582–6. Bibcode:1996Sci...271.1582P. CiteSeerX 10.1.1.34.7762. doi:10.1126/science.271.5255.1582. PMID 8599114. S2CID 13638059.
  21. ^ a b Smyth RP, Davenport MP, Mak J (November 2012). "The origin of genetic diversity in HIV-1". Virus Research. 169 (2): 415–29. doi:10.1016/j.virusres.2012.06.015. PMID 22728444.
  22. ^ Schmit JC, Cogniaux J, Hermans P, Van Vaeck C, Sprecher S, Van Remoortel B, et al. (November 1996). "Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain". The Journal of Infectious Diseases. 174 (5): 962–8. doi:10.1093/infdis/174.5.962. PMID 8896496.
  23. ^ Henkel J (July–August 1999). "Attacking AIDS with a 'cocktail' therapy". FDA Consumer. Food and Drug Administration, US Dept. of Health and Human Services. Archived from the original on 2009-01-14.
  24. ^ a b Bangsberg DR, Kroetz DL, Deeks SG (May 2007). "Adherence-resistance relationships to combination HIV antiretroviral therapy". Current HIV/AIDS Reports. 4 (2): 65–72. doi:10.1007/s11904-007-0010-0. PMID 17547827. S2CID 45429207.
  25. ^ "Fixed-dose combinations". AIDSmap. March 2011. Retrieved 2014-04-09.
  26. ^ Bangalore S, Kamalakkannan G, Parkar S, Messerli FH (August 2007). "Fixed-dose combinations improve medication compliance: a meta-analysis". The American Journal of Medicine. 120 (8): 713–9. doi:10.1016/j.amjmed.2006.08.033. PMID 17679131.
  27. ^ Onwumeh J, Okwundu CI, Kredo T (May 2017). "Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults". The Cochrane Database of Systematic Reviews. 5 (5): CD009818. doi:10.1002/14651858.CD009818.pub2. PMC 5458151. PMID 28542796.
  28. ^ Darbyshire J (1995). "Perspectives in drug therapy of HIV infection". Drugs. 49 Suppl 1 (Supplement 1): 1–3, discussion 38–40. doi:10.2165/00003495-199500491-00003. PMID 7614897. S2CID 754662.
  29. ^ a b Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A, Emini EA, Chodakewitz JA (September 1997). "Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy". The New England Journal of Medicine. 337 (11): 734–9. doi:10.1056/NEJM199709113371102. PMID 9287228.
  30. ^ Ho DD (August 1995). "Time to hit HIV, early and hard". The New England Journal of Medicine. 333 (7): 450–1. doi:10.1056/NEJM199508173330710. PMID 7616996.
  31. ^ Harrington M, Carpenter CC (June 2000). "Hit HIV-1 hard, but only when necessary". Lancet. 355 (9221): 2147–52. doi:10.1016/S0140-6736(00)02388-6. PMID 10902643. S2CID 22747572.
  32. ^ Sonenklar C (2011). "Chapter 6: Treatment for HIV and AIDS". AIDS. USA Today Health Reports: Diseases and Disorders. Minneapolis, MN: Twenty-First Century Books. pp. 90–101. ISBN 9780822585817.
  33. ^ a b Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. (April 2009). "Effect of early versus deferred antiretroviral therapy for HIV on survival". The New England Journal of Medicine. 360 (18): 1815–26. doi:10.1056/NEJMoa0807252. PMC 2854555. PMID 19339714.
  34. ^ Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, et al. (August 2015). "Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection". The New England Journal of Medicine. 373 (9): 795–807. doi:10.1056/NEJMoa1506816. PMC 4569751. PMID 26192873.
  35. ^ Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, et al. (August 2015). "A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa" (PDF). The New England Journal of Medicine. 373 (9): 808–22. doi:10.1056/NEJMoa1507198. hdl:10044/1/41218. PMID 26193126.
  36. ^ Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, et al. (March 2009). "Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment". Clinical Infectious Diseases. 48 (6): 787–94. doi:10.1086/597093. PMC 2720023. PMID 19193107.
  37. ^ Monforte A, Abrams D, Pradier C, Weber R, Reiss P, Bonnet F, et al. (October 2008). "HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies". AIDS. 22 (16): 2143–53. doi:10.1097/QAD.0b013e3283112b77. PMC 2715844. PMID 18832878.
  38. ^ a b c d "First long-acting injectable antiretroviral therapy for HIV recommended approval". European Medicines Agency (EMA) (Press release). 16 October 2020. Retrieved 16 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  39. ^ Graham SM, Holte SE, Peshu NM, Richardson BA, Panteleeff DD, Jaoko WG, et al. (February 2007). "Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding". AIDS. 21 (4): 501–7. doi:10.1097/QAD.0b013e32801424bd. PMID 17301569. S2CID 21335467.
  40. ^ Vernazza PL, Troiani L, Flepp MJ, Cone RW, Schock J, Roth F, et al. (January 2000). "Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study". AIDS. 14 (2): 117–21. CiteSeerX 10.1.1.567.3563. doi:10.1097/00002030-200001280-00006. PMID 10708281. S2CID 3035239.
  41. ^ Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. (August 2011). "Prevention of HIV-1 infection with early antiretroviral therapy". The New England Journal of Medicine. 365 (6): 493–505. doi:10.1056/NEJMoa1105243. PMC 3200068. PMID 21767103.
  42. ^ Cohen MS, Smith MK, Muessig KE, Hallett TB, Powers KA, Kashuba AD (November 2013). "Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?". Lancet. 382 (9903): 1515–24. doi:10.1016/S0140-6736(13)61998-4. PMC 3880570. PMID 24152938.
  43. ^ Cohen J (December 2011). "Breakthrough of the year. HIV treatment as prevention". Science. 334 (6063): 1628. Bibcode:2011Sci...334.1628C. doi:10.1126/science.334.6063.1628. PMID 22194547.
  44. ^ a b c "Consensus statement: Risk of Sexual Transmission of HIV from a Person Living with HIV who has an Undetectable Viral Load". Prevention Access Campaign. 21 July 2016. Retrieved 2 April 2019. Note: When the statement and list of endorsements was retrieved, it had last been updated on 23 August 2018 and included "over 850 organizations from nearly 100 countries."
  45. ^ a b c Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, van Lunzen J, et al. (July 2016). "Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy". JAMA. 316 (2): 171–81. doi:10.1001/jama.2016.5148. PMID 27404185. PARTNER (Partners of People on ART—A New Evaluation of the Risks)
  46. ^ a b c d e f Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection<. WHO. June 30, 2013. p. 38. ISBN 978-92-4-150572-7.
  47. ^ a b El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fätkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C (November 2006). "CD4+ count-guided interruption of antiretroviral treatment" (PDF). The New England Journal of Medicine. 355 (22): 2283–96. doi:10.1056/NEJMoa062360. PMID 17135583.
  48. ^ a b Silverberg MJ, Neuhaus J, Bower M, Gey D, Hatzakis A, Henry K, et al. (September 2007). "Risk of cancers during interrupted antiretroviral therapy in the SMART study". AIDS. 21 (14): 1957–63. doi:10.1097/QAD.0b013e3282ed6338. PMID 17721103. S2CID 16090838.
  49. ^ Günthard HF, Aberg JA, Eron JJ, Hoy JF, Telenti A, Benson CA, et al. (2014-07-23). "Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel". JAMA. 312 (4): 410–25. doi:10.1001/jama.2014.8722. PMID 25038359.
  50. ^ "EACS Guidelines 8.0". www.eacsociety.org. Retrieved 2016-01-14.
  51. ^ Cane P, Chrystie I, Dunn D, Evans B, Geretti AM, Green H, et al. (December 2005). "Time trends in primary resistance to HIV drugs in the United Kingdom: multicentre observational study". BMJ. 331 (7529): 1368. doi:10.1136/bmj.38665.534595.55. PMC 1309643. PMID 16299012.
  52. ^ Novak RM, Chen L, MacArthur RD, Baxter JD, Huppler Hullsiek K, Peng G, et al. (February 2005). "Prevalence of antiretroviral drug resistance mutations in chronically HIV-infected, treatment-naive patients: implications for routine resistance screening before initiation of antiretroviral therapy". Clinical Infectious Diseases. 40 (3): 468–74. doi:10.1086/427212. PMID 15668873.
  53. ^ Descamps D, Assoumou L, Chaix ML, Chaillon A, Pakianather S, de Rougemont A, et al. (November 2013). "National sentinel surveillance of transmitted drug resistance in antiretroviral-naive chronically HIV-infected patients in France over a decade: 2001-2011". The Journal of Antimicrobial Chemotherapy. 68 (11): 2626–31. doi:10.1093/jac/dkt238. PMID 23798669.
  54. ^ Sungkanuparph S, Pasomsub E, Chantratita W (Jan–Feb 2014). "Surveillance of transmitted HIV drug resistance in antiretroviral-naive patients aged less than 25 years, in Bangkok, Thailand". Journal of the International Association of Providers of AIDS Care. 13 (1): 12–4. doi:10.1177/2325957413488200. PMID 23708678.
  55. ^ Gagliardo C, Brozovich A, Birnbaum J, Radix A, Foca M, Nelson J, et al. (March 2014). "A multicenter study of initiation of antiretroviral therapy and transmitted drug resistance in antiretroviral-naive adolescents and young adults with HIV in New York City". Clinical Infectious Diseases. 58 (6): 865–72. doi:10.1093/cid/ciu003. PMC 3988426. PMID 24429431.
  56. ^ Pérez L, Kourí V, Alemán Y, Abrahantes Y, Correa C, Aragonés C, et al. (June 2013). "Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba". Infection, Genetics and Evolution. 16: 144–50. doi:10.1016/j.meegid.2013.02.002. PMID 23416260.
  57. ^ Mbuagbaw L, Mursleen S, Irlam JH, Spaulding AB, Rutherford GW, Siegfried N, et al. (Cochrane Infectious Diseases Group) (December 2016). "Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals". The Cochrane Database of Systematic Reviews. 12: CD004246. doi:10.1002/14651858.CD004246.pub4. PMC 5450880. PMID 27943261.
  58. ^ a b c d "Antiretroviral Therapy for Human Immunodeficiency Virus Infection". Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (7th ed.). Churchill Livingstone. 2009. ISBN 978-0-443-06839-3.
  59. ^ Lepist EI, Phan TK, Roy A, Tong L, Maclennan K, Murray B, Ray AS (October 2012). "Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro". Antimicrobial Agents and Chemotherapy. 56 (10): 5409–13. doi:10.1128/AAC.01089-12. PMC 3457391. PMID 22850510.
  60. ^ Fidler S, Porter K, Ewings F, Frater J, Ramjee G, Cooper D, et al. (January 2013). "Short-course antiretroviral therapy in primary HIV infection". The New England Journal of Medicine. 368 (3): 207–17. doi:10.1056/NEJMoa1110039. PMC 4131004. PMID 23323897.
  61. ^ Hollingsworth TD, Anderson RM, Fraser C (September 2008). "HIV-1 transmission, by stage of infection". The Journal of Infectious Diseases. 198 (5): 687–93. doi:10.1086/590501. PMID 18662132.
  62. ^ Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F (October 8, 2004). "Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis". Lancet. 364 (9441): 1236–43. doi:10.1016/S0140-6736(04)17140-7. PMID 15464184. S2CID 24511465.
  63. ^ a b "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection" (PDF). US Department of Health and Human Services. February 12, 2014. pp. 50–61. Retrieved April 11, 2014.
  64. ^ Musiime V, Ssali F, Kayiwa J, Namala W, Kizito H, Kityo C, Mugyenyi P (October 2009). "Response to nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-infected children with perinatal exposure to single-dose nevirapine". AIDS Research and Human Retroviruses. 25 (10): 989–96. doi:10.1089/aid.2009.0054. PMID 19778270.
  65. ^ Violari A, Lindsey JC, Hughes MD, Mujuru HA, Barlow-Mosha L, Kamthunzi P, et al. (June 2012). "Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children". The New England Journal of Medicine. 366 (25): 2380–9. doi:10.1056/NEJMoa1113249. PMC 3443859. PMID 22716976.
  66. ^ Adetokunboh OO, Schoonees A, Balogun TA, Wiysonge CS (October 2015). "Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis". BMC Infectious Diseases. 15 (1): 469. doi:10.1186/s12879-015-1183-6. PMC 4623925. PMID 26502899.
  67. ^ Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J, Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF (August 1999). "Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group". The New England Journal of Medicine. 341 (6): 394–402. doi:10.1056/NEJM199908053410602. PMID 10432324.
  68. ^ a b European Collaborative Study (February 2005). "Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy". Clinical Infectious Diseases. 40 (3): 458–65. doi:10.1086/427287. PMID 15668871.
  69. ^ a b "Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States" (PDF). US DHHS. March 28, 2014. Retrieved 2014-04-11.
  70. ^ Rousseau CM, Nduati RW, Richardson BA, Steele MS, John-Stewart GC, Mbori-Ngacha DA, et al. (March 2003). "Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease". The Journal of Infectious Diseases. 187 (5): 741–7. doi:10.1086/374273. PMC 3384731. PMID 12599047.
  71. ^ May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S, et al. (May 2014). "Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy". AIDS. 28 (8): 1193–202. doi:10.1097/QAD.0000000000000243. PMC 4004637. PMID 24556869.
  72. ^ Nakagawa F, May M, Phillips A (February 2013). "Life expectancy living with HIV: recent estimates and future implications". Current Opinion in Infectious Diseases. 26 (1): 17–25. doi:10.1097/QCO.0b013e32835ba6b1. PMID 23221765. S2CID 7554571.
  73. ^ Silverberg MJ, Leyden W, Horberg MA, DeLorenze GN, Klein D, Quesenberry CP (April 2007). "Older age and the response to and tolerability of antiretroviral therapy". Archives of Internal Medicine. 167 (7): 684–91. doi:10.1001/archinte.167.7.684. PMID 17420427.
  74. ^ Althoff KN, Justice AC, Gange SJ, Deeks SG, Saag MS, Silverberg MJ, Gill MJ, Lau B, Napravnik S, Tedaldi E, Klein MB, Gebo KA (October 2010). "Virologic and immunologic response to HAART, by age and regimen class". AIDS. 24 (16): 2469–79. doi:10.1097/QAD.0b013e32833e6d14. PMC 3136814. PMID 20829678.
  75. ^ a b Greene M, Justice AC, Lampiris HW, Valcour V (April 2013). "Management of human immunodeficiency virus infection in advanced age". JAMA. 309 (13): 1397–405. doi:10.1001/jama.2013.2963. PMC 3684249. PMID 23549585.
  76. ^ a b Eshun-Wilson I, Siegfried N, Akena DH, Stein DJ, Obuku EA, Joska JA (January 2018). "Antidepressants for depression in adults with HIV infection". The Cochrane Database of Systematic Reviews. 1 (1): CD008525. doi:10.1002/14651858.CD008525.pub3. PMC 6491182. PMID 29355886.
  77. ^ Gardner EM, Burman WJ, Steiner JF, Anderson PL, Bangsberg DR (June 2009). "Antiretroviral medication adherence and the development of class-specific antiretroviral resistance". AIDS. 23 (9): 1035–46. doi:10.1097/QAD.0b013e32832ba8ec. PMC 2704206. PMID 19381075.
  78. ^ "Global Price Reporting Mechanism for HIV, tuberculosis and malaria". World Health Organization. Retrieved 2014-04-11.
  79. ^ "Antiretroviral Drug Prices". Avert. Retrieved 2014-04-12.
  80. ^ "New one-pill, $10-per-month anti-retroviral AIDS treatment debuts in South Africa". The Raw Story. Agence France-Presse. 2013.
  81. ^ Walensky RP, Ross EL, Kumarasamy N, Wood R, Noubary F, Paltiel AD, et al. (October 2013). "Cost-effectiveness of HIV treatment as prevention in serodiscordant couples". The New England Journal of Medicine. 369 (18): 1715–25. doi:10.1056/NEJMsa1214720. PMC 3913536. PMID 24171517.
  82. ^ Horn T (August 28, 2012). "Activists Protest Stribild's $28,500 Price Tag". AIDSMeds. Retrieved 2014-04-11.
  83. ^ "Stribild". GoodRx. Retrieved 2014-04-11.
  84. ^ Beardsley T (July 1998). "Coping with HIV's ethical dilemmas". Scientific American. 279 (1): 106–7. Bibcode:1998SciAm.279a.106B. doi:10.1038/scientificamerican0798-106. PMID 9648307.
  85. ^ a b c Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, et al. (July 2012). "Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel". JAMA. 308 (4): 387–402. doi:10.1001/jama.2012.7961. PMID 22820792. S2CID 205038135.
  86. ^ Murray JS, Elashoff MR, Iacono-Connors LC, Cvetkovich TA, Struble KA (May 1999). "The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs". AIDS. 13 (7): 797–804. doi:10.1097/00002030-199905070-00008. PMID 10357378.
  87. ^ Swiss National AIDS Commission (15 October 2016). "The Swiss statement". HIV i-Base. Retrieved 2 April 2019.
  88. ^ The Lancet Hiv (November 2017). "U=U taking off in 2017". Editorial. The Lancet. HIV. 4 (11): e475. doi:10.1016/S2352-3018(17)30183-2. PMID 29096785.
  89. ^ "Can't Pass It On". Terrence Higgins Trust. 2019. Archived from the original on 7 April 2019. Retrieved 2 April 2019.
  90. ^ a b c d Hoffman H (10 January 2019). "The science is clear: with HIV, undetectable equals untransmittable" (Press release). National Institutes of Health. National Institute of Allergy and Infectious Diseases. Retrieved 3 May 2019. NIAID Director Anthony S. Fauci, M.D., and colleagues summarize results from large clinical trials and cohort studies validating U=U. The landmark NIH-funded HPTN 052 clinical trial showed that no linked HIV transmissions occurred among HIV serodifferent heterosexual couples when the partner living with HIV had a durably suppressed viral load. Subsequently, the PARTNER and Opposites Attract studies confirmed these findings and extended them to male-male couples. ... The success of U=U as an HIV prevention method depends on achieving and maintaining an undetectable viral load by taking ART daily as prescribed.
  91. ^ Bavinton BR, Pinto AN, Phanuphak N, Grinsztejn B, Prestage GP, Zablotska-Manos IB, et al. (August 2018). "Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study". The Lancet. HIV. 5 (8): e438–e447. doi:10.1016/S2352-3018(18)30132-2. PMID 30025681.
  92. ^ a b c Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, Degen O, et al. (May 2019). "Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study". Lancet. 393 (10189): 2428–2438. doi:10.1016/S0140-6736(19)30418-0. PMC 6584382. PMID 31056293.
  93. ^ Rodger, A. (for the PARTNER study group) (July 2018). Risk of HIV transmission through condomless sex in MSM couples with suppressive ART: The PARTNER2 Study extended results in gay men. AIDS2018: 22nd International AIDS Conference. Amsterdam, the Netherlands. Retrieved 2 April 2019.
  94. ^ Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. (September 2016). "Antiretroviral Therapy for the Prevention of HIV-1 Transmission". The New England Journal of Medicine. 375 (9): 830–9. doi:10.1056/NEJMoa1600693. PMC 5049503. PMID 27424812.
  95. ^ Hodson M (17 November 2017). U=U: Talking to patients about transmission risk (PDF). British HIV Association Autumn Conference 2017. Retrieved 3 May 2019. (abstract for presentation on behalf of NAM / AIDSmap)
  96. ^ Boseley S, Devlin H (3 May 2019). "End to AIDS in sight as huge study finds drugs stop HIV transmission". The Guardian. Retrieved 3 May 2019.
  97. ^ Hughes MD, Stein DS, Gundacker HM, Valentine FT, Phair JP, Volberding PA (January 1994). "Within-subject variation in CD4 lymphocyte count in asymptomatic human immunodeficiency virus infection: implications for patient monitoring". The Journal of Infectious Diseases. 169 (1): 28–36. doi:10.1093/infdis/169.1.28. PMID 7903975.
  98. ^ Lok JJ, Bosch RJ, Benson CA, Collier AC, Robbins GK, Shafer RW, Hughes MD (July 2010). "Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection". AIDS. 24 (12): 1867–76. doi:10.1097/QAD.0b013e32833adbcf. PMC 3018341. PMID 20467286.
  99. ^ Gazzola L, Tincati C, Bellistrì GM, Monforte A, Marchetti G (February 2009). "The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options". Clinical Infectious Diseases. 48 (3): 328–37. doi:10.1086/695852. PMID 19123868.
  100. ^ Kløverpris HN, Kazer SW, Mjösberg J, Mabuka JM, Wellmann A, Ndhlovu Z, et al. (February 2016). "Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression". Immunity. 44 (2): 391–405. doi:10.1016/j.immuni.2016.01.006. PMC 6836297. PMID 26850658.
  101. ^ Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA, Kunisawa J, et al. (June 2012). "Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria". Science. 336 (6086): 1321–5. Bibcode:2012Sci...336.1321S. doi:10.1126/science.1222551. PMC 3659421. PMID 22674331.
  102. ^ Chung CY, Alden SL, Funderburg NT, Fu P, Levine AD (June 2014). "Progressive proximal-to-distal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals". PLOS Pathogens. 10 (6): e1004198. doi:10.1371/journal.ppat.1004198. PMC 4072797. PMID 24968145.
  103. ^ "Stanford University HIV Drug Resistance Database". Retrieved 2014-04-13.
  104. ^ Aves T, Tambe J, Siemieniuk RA, Mbuagbaw L, et al. (Cochrane Infectious Diseases Group) (November 2018). "Antiretroviral resistance testing in HIV-positive people". The Cochrane Database of Systematic Reviews. 11: CD006495. doi:10.1002/14651858.CD006495.pub5. PMC 6517236. PMID 30411789.
  105. ^ Miller V, Cozzi-Lepri A, Hertogs K, Gute P, Larder B, Bloor S, et al. (March 2000). "HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort". Antiviral Therapy. 5 (1): 49–55. PMID 10846593.
  106. ^ a b c Simon V, Ho DD, Abdool Karim Q (August 2006). "HIV/AIDS epidemiology, pathogenesis, prevention, and treatment". Lancet. 368 (9534): 489–504. doi:10.1016/S0140-6736(06)69157-5. PMC 2913538. PMID 16890836.
  107. ^ Johnson AA, Ray AS, Hanes J, Suo Z, Colacino JM, Anderson KS, Johnson KA (November 2001). "Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase". The Journal of Biological Chemistry. 276 (44): 40847–57. doi:10.1074/jbc.M106743200. PMID 11526116.
  108. ^ Birkus G, Hitchcock MJ, Cihlar T (March 2002). "Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors". Antimicrobial Agents and Chemotherapy. 46 (3): 716–23. doi:10.1128/aac.46.3.716-723.2002. PMC 127499. PMID 11850253.
  109. ^ Hulgan, T., Robbins, G.K., Kalams, S.A., Samuels, D.C., Grady, B., Shafer, R. et al. (2012) T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. PLoS One 7, e43803 https://doi.org/10.1371/journal.pone.0043803
  110. ^ Guzman-Fulgencio, M., Berenguer, J., Micheloud, D., Fernandez-Rodriguez, A., Garcia-Alvarez, M., Jimenez-Sousa, M.A. et al. (2013) European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy. J. Antimicrob. Chemother. 68, 2349–2357 https://doi.org/10.1093/jac/dkt206
  111. ^ Hart, A.B., Samuels, D.C. and Hulgan, T. (2013) The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy. AIDS Rev. 15, 213–220 PMID: https://pubmed.ncbi.nlm.nih.gov/24322381/
  112. ^ Mitochondrial haplogroup H is related to CD4+ T cell recovery in HIV infected patients starting combination antiretroviral therapy
  113. ^ Boelsterli, U.A. and Lim, P.L.K. (2007) Mitochondrial abnormalities—a link to idiosyncratic drug hepatotoxicity? Toxicol. Appl. Pharmacol. 220, 92–107 https://doi.org/10.1016/j.taap.2006.12.013
  114. ^ Usach I, Melis V, Peris JE (September 2013). "Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability". Journal of the International AIDS Society. 16 (1): 18567. doi:10.7448/ias.16.1.18567. PMC 3764307. PMID 24008177.
  115. ^ Walmsley S (June 2007). "Protease inhibitor-based regimens for HIV therapy: safety and efficacy". Journal of Acquired Immune Deficiency Syndromes. 45 Suppl 1 (Supplement 1): S5–13, quiz S28–31. doi:10.1097/QAI.0b013e3180600709. PMID 17525691. S2CID 3113311.
  116. ^ Lee FJ, Carr A (September 2012). "Tolerability of HIV integrase inhibitors". Current Opinion in HIV and AIDS. 7 (5): 422–8. doi:10.1097/COH.0b013e328356682a. PMID 22886031. S2CID 29497910.
  117. ^ Bell DM (May 1997). "Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview". The American Journal of Medicine. 102 (5B): 9–15. doi:10.1016/s0002-9343(97)89441-7. PMID 9845490.
  118. ^ Ippolito G, Puro V, De Carli G (June 1993). "The risk of occupational human immunodeficiency virus infection in health care workers. Italian Multicenter Study. The Italian Study Group on Occupational Risk of HIV infection". Archives of Internal Medicine. 153 (12): 1451–8. doi:10.1001/archinte.1993.00410120035005. PMID 8512436.
  119. ^ a b c Kuhar DT, Henderson DK, Struble KA, Heneine W, Thomas V, Cheever LW, Gomaa A, Panlilio AL (September 2013). "Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis". Infection Control and Hospital Epidemiology. 34 (9): 875–92. doi:10.1086/672271. JSTOR 672271. PMID 23917901. S2CID 17032413.
  120. ^ Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, et al. (November 1997). "A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group". The New England Journal of Medicine. 337 (21): 1485–90. doi:10.1056/NEJM199711203372101. PMID 9366579.
  121. ^ Glynn JR, Buvé A, Caraël M, Kahindo M, Macauley IB, Musonda RM, Jungmann E, Tembo F, Zekeng L (December 2000). "Decreased fertility among HIV-1-infected women attending antenatal clinics in three African cities". Journal of Acquired Immune Deficiency Syndromes. 25 (4): 345–52. doi:10.1097/00126334-200012010-00008. PMID 11114835. S2CID 22980353.
  122. ^ a b Savasi V, Mandia L, Laoreti A, Cetin I (2012). "Reproductive assistance in HIV serodiscordant couples". Human Reproduction Update. 19 (2): 136–50. doi:10.1093/humupd/dms046. PMID 23146867.
  123. ^ Centers for Disease Control (CDC) (April 1990). "HIV-1 infection and artificial insemination with processed semen". MMWR. Morbidity and Mortality Weekly Report. 39 (15): 249, 255–6. PMID 2109169.
  124. ^ Savasi V, Ferrazzi E, Lanzani C, Oneta M, Parrilla B, Persico T (March 2007). "Safety of sperm washing and ART outcome in 741 HIV-1-serodiscordant couples". Human Reproduction. 22 (3): 772–7. doi:10.1093/humrep/del422. PMID 17107974.
  125. ^ Coutsoudis A, Kwaan L, Thomson M (October 2010). "Prevention of vertical transmission of HIV-1 in resource-limited settings". Expert Review of Anti-Infective Therapy. 8 (10): 1163–75. doi:10.1586/eri.10.94. PMID 20954881. S2CID 46624541.
  126. ^ "U.S Approves Drug to Prolong Lives of AIDS Patients". New York Times. 1987-03-21.
  127. ^ Institute of Medicine (US) Committee for the Oversight of AIDS Activities (1988). Confronting AIDS. doi:10.17226/771. ISBN 978-0-309-03879-9. PMID 25032454.
  128. ^ Moore RD, Chaisson RE (April 1996). "Natural history of opportunistic disease in an HIV-infected urban clinical cohort". Annals of Internal Medicine. 124 (7): 633–42. doi:10.7326/0003-4819-124-7-199604010-00003. PMID 8607591. S2CID 20023137.
  129. ^ Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. (September 1997). "A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team". The New England Journal of Medicine. 337 (11): 725–33. doi:10.1056/NEJM199709113371101. PMID 9287227. S2CID 24043435.
  130. ^ a b Sifris D, Myhre J (2017), When Did HAART Become ART? Change Is About More Than Just Semantics [reviewed by a board-certified physician].
  131. ^ a b c Passaes CP, Sáez-Cirión A (April 2014). "HIV cure research: advances and prospects" (PDF). Virology. 454–455: 340–52. doi:10.1016/j.virol.2014.02.021. PMID 24636252.
  132. ^ Rosenberg T (May 29, 2011). "The Man Who Had HIV and Now Does Not". New York Magazine. Retrieved 2014-04-12.
  133. ^ Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, et al. (February 2009). "Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation". The New England Journal of Medicine. 360 (7): 692–8. doi:10.1056/NEJMoa0802905. PMID 19213682. S2CID 14905671.
  134. ^ Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (March 2014). "Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV". The New England Journal of Medicine. 370 (10): 901–10. doi:10.1056/NEJMoa1300662. PMC 4084652. PMID 24597865.
  135. ^ HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene Aridaman Pandit & Rob J. de Boer. Scientific Reports volume 5, Article number: 18088 (2016)
  136. ^ Senthilingam M (18 July 2016). "HIV cure study provides insight into 2008 case". CNN. Retrieved 21 July 2016.
  137. ^ Darmanin M (21 July 2016). "No trace of HIV virus after successful stem cell transplantation". UtrechtCentral.com. Retrieved 21 July 2016.
  138. ^ "2016 Towards an HIV Cure Symposium Programme. 16 & 17 July 2016" (PDF). Durban International Convention Centre (ICC), Durban, South Africa: AIDS Society (IAS). 21 June 2016. Retrieved 21 July 2016.
  139. ^ Levin, Jules (19 July 2016). "Allogeneic Stem Cell Transplantation in HIV-1 infected individuals; the EpiStem Consortium [Conference Reports for NATAP] [IAS Durban HIV cure Symposium July 16–17 2016]". National AIDS Treatment Advocacy Project (NATAP). Retrieved 23 July 2016.
  140. ^ Johnson C (5 March 2019). "A decade after the first person was cured of HIV, a second patient is in long-term remission". The Washington Post. Retrieved 5 March 2019.
  141. ^ May A (5 March 2019). "HIV patient seemingly cured in second remarkable case, London doctors report". USA Today. Retrieved 5 March 2019.
  142. ^ Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, et al. (August 2009). "HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation". Nature Medicine. 15 (8): 893–900. doi:10.1038/nm.1972. PMC 2859814. PMID 19543283.
  143. ^ McNeil, Donald (2014). "Early Treatment Is Found to Clear H.I.V. in a 2nd Baby". New York Times.
  144. ^ Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M, Chun TW, et al. (November 2013). "Absence of detectable HIV-1 viremia after treatment cessation in an infant". The New England Journal of Medicine. 369 (19): 1828–35. doi:10.1056/NEJMoa1302976. PMC 3954754. PMID 24152233.
  145. ^ Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM (February 2010). "Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection". PLOS ONE. 5 (2): e9390. Bibcode:2010PLoSO...5.9390A. doi:10.1371/journal.pone.0009390. PMC 2826423. PMID 20186346.
  146. ^ Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et al. (July 2012). "Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy". Nature. 487 (7408): 482–5. Bibcode:2012Natur.487..482A. doi:10.1038/nature11286. PMC 3704185. PMID 22837004.
  147. ^ Carcelain G, Autran B (July 2013). "Immune interventions in HIV infection". Immunological Reviews. 254 (1): 355–71. doi:10.1111/imr.12083. PMID 23772631. S2CID 34104811.
  148. ^ "Programs TAT – Vaccin VIH | BIOSANTECH SA ®". www.biosantech.org. Retrieved 2015-10-27.
  149. ^ Watkins JD, Lancelot S, Campbell GR, Esquieu D, de Mareuil J, Opi S, et al. (January 2006). "Reservoir cells no longer detectable after a heterologous SHIV challenge with the synthetic HIV-1 Tat Oyi vaccine". Retrovirology. 3: 8. doi:10.1186/1742-4690-3-8. PMC 1434768. PMID 16441880.
  150. ^ Kallen A, Woloshin S, Shu J, Juhl E, Schwartz L (2007-10-01). "Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report". Health Affairs. 26 (5): 1392–8. doi:10.1377/hlthaff.26.5.1392. PMID 17848450. S2CID 12536749.
  151. ^ Josefson D (May 2001). "FDA warning to manufacturers of AIDS drugs". BMJ. 322 (7295): 1143. doi:10.1136/bmj.322.7295.1143. PMC 1120280. PMID 11348904.
  152. ^ "Constitution". www.who.int. Retrieved 2019-03-07.
  153. ^ a b Miners A, Phillips A, Kreif N, Rodger A, Speakman A, Fisher M, et al. (October 2014). "Health-related quality-of-life of people with HIV in the era of combination antiretroviral treatment: a cross-sectional comparison with the general population". The Lancet. HIV. 1 (1): e32-40. doi:10.1016/S2352-3018(14)70018-9. PMID 26423814.
  154. ^ a b Gakhar H, Kamali A, Holodniy M (May 2013). "Health-related quality of life assessment after antiretroviral therapy: a review of the literature". Drugs. 73 (7): 651–72. doi:10.1007/s40265-013-0040-4. PMC 4448913. PMID 23591907.
  155. ^ a b Mak WW, Poon CY, Pun LY, Cheung SF (July 2007). "Meta-analysis of stigma and mental health". Social Science & Medicine. 65 (2): 245–61. doi:10.1016/j.socscimed.2007.03.015. PMID 17462800.
  156. ^ a b Wolfe D, Carrieri MP, Shepard D (July 2010). "Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward". Lancet. 376 (9738): 355–66. doi:10.1016/S0140-6736(10)60832-X. PMID 20650513. S2CID 13205040.
  157. ^ van der Heijden I, Abrahams N, Sinclair D, et al. (Cochrane Infectious Diseases Group) (March 2017). "Psychosocial group interventions to improve psychological well-being in adults living with HIV". The Cochrane Database of Systematic Reviews. 3: CD010806. doi:10.1002/14651858.CD010806.pub2. PMC 5461871. PMID 28291302.
  158. ^ "HIV/AIDS in NYC" (PDF).
  159. ^ "Health Equity".

External links

  • AIDSinfo – Comprehensive resource for HIV/AIDS treatment and clinical trial information from the U. S. Department of Health and Human Services
  • ASHM – Australian Commentary on HHS Guidelines for the use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
  • Origins of antiretroviral combination therapy
  • Viral Load research papers, including effectiveness of HAART on reducing viral load
  • Current status of gene therapy strategies to treat HIV/AIDS