Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in fixed-dose combinations as initial treatment for HIV patients: a systematic review and network meta-analysis / Zidovudina/Lamivudina vs Abacavir/Lamivudina vs Tenofovir/Emtricitabina en combinaciones de dosis fija como tratamiento inicial en pacientes con VIH: revisión sistemática y metanálisis en red

Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Prevalence and Risk Factors of Low Bone Mineral Density in Korean HIV-Infected Patients: Impact of Abacavir and Zidovudine

Low bone mineral density (BMD) is common in HIV-infected patients. We aimed to describe the prevalence of low BMD and risk factors in Korean HIV-infected patients and to assess the effects of antiretroviral therapy (ART) on BMD. We retrospectively evaluated 224 HIV infected-patients. The prevalence of osteopenia and osteoporosis were 41.5% and 12.9%. These were much higher in 53 patients aged 50 yr and older (52.8% and 34.0%). Older age, lower body mass index, and ART > 3 months were independent risk factors for low BMD. Osteoporosis was more prevalent in patients on the abacavir-based regimen for or = 1 yr; however, it was more prevalent in patients on the zidovudine-based regimen for > or = 1 yr than < 1 yr (P = 0.017). Osteoporosis in patients on the abacavir-based regimen was more common in the spine than in the femur (P = 0.01). Given such a high prevalence of low BMD, close monitoring of BMD for HIV-infected patients on ART is required. The different prevalence of osteoporosis over time and affected areas between two regimens suggest they may play roles in different mechanisms in bone loss.

Impacto do tratamento antirretroviral na ocorrência de macrocitose em pacientes com HIV/AIDS do município de Maringá, Estado do Paraná / Impact of antiretroviral therapy on occurrences of macrocytosis in patients with HIV/AIDS in Maringá, State of Paraná

INTRODUÇÃO: AIDS é uma doença causada pelo HIV que compromete o sistema imune do organismo. O advento da terapia antirretroviral (TARV) altamente eficaz promoveu melhora substancial do prognóstico da doença e da qualidade de vida dos pacientes com HIV/AIDS. Durante seu tratamento prolongado, notam-se algumas alterações hematológicas, dentre elas, anemia e macrocitose, bem como carências de micronutrientes, tais como, de vitamina B12 e ácido fólico. O objetivo do presente trabalho é relacionar a macrocitose e anemia ao uso de TARV, ou à deficiência de vitamina B12 ou de ácido fólico. MÉTODOS: Foram avaliados 110 pacientes HIV positivos, comparando-se aqueles em uso de TARV com zidovudina (AZT) (grupo 1), TARV sem AZT (grupo 2) ou sem uso de TARV (grupo 3). RESULTADOS: Os pacientes dos três grupos não apresentaram diferenças estatísticas significativas quanto aos níveis de hemoglobina (p = 0,584) e de ácido fólico (p = 0,956). Os pacientes do grupo 1 (G1) apresentaram volume corpuscular médio (VCM) aumentado quando comparado ao grupo 3 (G3) (p < 0,05), bem como do grupo 2 (G2) em relação ao G3 (p < 0,001). As dosagens de vitamina B12 do G1 e G3 foram menores do que as encontradas pelo G2 (p = 0,008). CONCLUSÕES: Conclui-se que os indivíduos em uso de TARV apresentaram macrocitose, embora não pudesse ser relacionada ao tipo de TARV ou a deficiência de vitamina B12. Entretanto, a deficiência de ácido fólico não esteve relacionada ao uso de TARV e nem à macrocitose.

INTRODUCTION: AIDS is a disease caused by HIV that compromises the organism's immune system. The advent of highly active antiretroviral therapy (HAART) has promoted substantial improvement in the prognosis for this disease and in HIV/AIDS patients' quality of life. During prolonged treatment, certain hematological disorders are observed, such as anemia and macrocytosis, as well as deficiencies of micronutrient such as vitamin B12 and folic acid. The objective of this study was to correlate the presence of macrocytosis and anemia with HAART use or vitamin B12 and folic acid deficiencies. METHODS: 110 HIV-positive patients were included, in three groups: HAART use with zidovudine (AZT) (group 1), HAART use without AZT (group 2) and no HAART (group 3). RESULTS: None of the patients in any of the three groups presented statistically significant differences relating to hemoglobin level (p = 0.584) or folic acid level (p = 0.956). Group 1 (G1) had a higher mean corpuscular volume (MCV) than G3 (p < 0.05), and group 2 (G2) had a higher volume than group 3 (G3) (p < 0.001). Vitamin B12 levels in G1 and G3 were smaller than those in G2 (p = 0.008). CONCLUSIONS: It was concluded that patients undergoing HAART treatment presented macrocytosis, even though this could not be correlated with the type of HAART or with vitamin B12 deficiency. However, folic acid deficiency was unrelated to either HAART or macrocytosis.

High incidence of zidovudine induced anaemia in HIV infected patients in eastern India.

Background & objectives: Zidovudine (ZDV) is the preferred nucleoside reverse transcriptase inhibitor in the first line antiretroviral regimen in India. It is known to be associated with life threatening toxicity like anaemia. This study was aimed at determining the prevalence of ZDV induced anaemia in HIV infected patients initiated on ZDV containing antiretroviral therapy regimen and also to find out the correlates, if any, for causing ZDV induced anaemia. Methods: This retrospective study was carried in ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi between March 2005 to December 2007. HIV infected patients registered at ART Centre were treated according to guidelines of National AIDS Control Organization (NACO). Patients (n=1256) with haemoglobin (Hb) >8 g/dl were prescribed ZDV based antiretroviral therapy regimens. Patients developing anaemia (<8 g/dl) with other causes of anaemia excluded were recorded. Correlation of baseline characteristics (age, gender, haemoglobin levels, weight, CD4 counts and WHO clinical stage) with risk of developing anaemia was also calculated. Results: Two hundred three (16.2%) patients on ZDV regimen developed anaemia (<8 g%); 7.9 per cent (n=100) of these developed severe anaemia (<6.5 g%). Females were more prone to develop anaemia (P=0.026). Age, weight, WHO clinical stage and CD4 counts had no relation to development of anaemia. Interpretation & conclusion: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDV based antiretroviral regimens.

Que choisir en premiere ligne dans le traitement du VIH-1

Chaque annee; de nouveaux medicaments antiretroviraux sont mis sur le marche international. La lettre du CEDIM suit l'evolution du benefice et des risque de ces substances.En fin 2009; qu'est ce qui a progresse en termes de choix des medicaments chez les adultes infectes par le VIH-1?

Safety of antiretroviral drug therapy in Jamaican children with HIV/AIDS / Seguridad de la terapia con medicamento antiretroviral en niños jamaicanos con VIH/SIDA

BACKGROUND: HIV has been a leading cause of death in Jamaican children aged # five years. Antiretroviral drugs (ARVs) are increasingly available in Jamaica through the Global Fund. Adverse effects of ARVs are a major cause for non-adherence to medications. Knowledge of the use and side effects of these drugs are crucial in the management of HIV-infected children as we scale-up the use of antiretroviral therapy, islandwide. We evaluated the adverse events and safety of antiretroviral therapy in children attending four Infectious Disease Clinics in Kingston, Jamaica, a resource limited setting. METHODS: Data for children prospectively enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme during September 2002 to April 2005 were analyzed. RESULTS: Among 121 HIV-infected children, 77 (64%) were on ARVs, 90% had CDC class C disease, 60% were males and perinatal transmission predominated. AZT/3TC based regime was utilized in 93%, trimethoprim/sulphamethoxazole prophylaxis was used in 100% and five were completing anti-tuberculous drugs. Anaemia occurred in all patients, with increased severity in those on ARVs. Macrocytosis occurred in 83% and thrombocytopenia in 8% of those on ARVs. Elevation of bilirubin, aspartate transaminase (AST) and alanine transaminase (ALT) levels and reversed albumin to globulin ratio prior to commencing ARVs, with significantly lower prevalence following use of ARVs emphasized the severity of HIV disease at time of ARV initiation. Clinical adverse reactions were uncommon and included nail discoloration (8%), vomiting (7%), nausea (3%), peripheral lipodystrophy (4%) and abnormal dreams (1%). Ten children required change of ARV medication because of severe adverse effects: three for severe anaemia with repeat blood transfusions, three for severe nevirapine-associated rash and four for indinavir-associated haematuria. CONCLUSIONS: ARVs are being successfully initiated in HIV-infected Jamaican children using the public health model. The excellent safety profile, good tolerance and few reported significant adverse effects augur well as antiretroviral therapy is scaled-up islandwide.

ANTECEDENTES: EL VIH ha sido la principal causa de muerte en los niños jamaicanos de # cinco años de edad. Las drogas antiretrovirales (ARVs) se hallan cada vez más a disposición en Jamaica a través del Fondo Global. Los efectos adversos de los ARVs constituyen una causa fundamental para la no adherencia a los medicamentos. El conocimiento del uso y los efectos colaterales de estos medicamentos son cruciales para el tratamiento de los niños infectados por VIH en la medida en que escalamos el uso de la terapia antiretroviral a lo largo de toda la isla. Evaluamos los eventos adversos y la seguridad de la terapia antiretroviral en niños que asisten a cuatro clínicas de enfermedades infecciosas en Kingston, Jamaica, las cuales constituyen un escenario limitado en recursos. MÉTODOS: Se analizaron los datos de niños prospectivamente alistados en el Programa VIH/SIDA Prenatal y Pediátrico de Kingston, Jamaica, durante septiembre de 2002 hasta abril de 2005. RESULTADOS: Entre los 121 niños infectados con VIH, 77 (64%) estaban bajo medicación con ARVs, 90% tenían enfermedades del subgrupo C según la clasificación de CDC, 60% eran varones y predominó la transmisión perinatal. El régimen basado en AZT/3TC fue utilizado en 93%, trimeto-prima/sulfametoxazol se usó en el 100%, y cinco estaban completando medicamentos antituberculosos. La anemia estaba presente en todos los pacientes, con mayor severidad en aquellos bajo ARVs. Se observó macrocitosis en el 83% y trombocitopenia en un 8% de los que se hallaban bajo ARVs. La elevación de los niveles de bilirrubina, aspartato transaminasa (AST) y alanina transaminasa (ALT) y la relación albúmina/globulina invertida antes de comenzar con los ARVs, con una prevalencia significativamente menor tras el uso de los ARVs, enfatizaron la severidad de la enfermedad del VIH al momento de la iniciación del ARV. Las reacciones clínicas adversas fueron poco común e incluyeron decoloración de las uñas (8%), vómitos (7%), náuseas (3%), lipodistrofia periférica (4%) y sueños anormales (1%). Diez de los niños necesitaron cambio de medicación ARV debido a los severos efectos adversos: tres a causa de una anemia severa con repetidas transfusiones de sangre, tres debido a una severa erupción asociada con la nevirapina, y cuatro a causa de hematuria asociada con indinavir. CONCLUSIONES: Los medicamentos ARVs han comenzado a ser administrados exitosamente en niños jamaicanos infectados por el VIH, usando el modelo de salud pública. El excelente perfil de seguridad, la buena tolerancia y el pequeño número de efectos adversos significativos reportados, auguran un buen futuro a la escalada de la terapia antiretroviral en toda la isla.

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20 percent, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20 percent. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Estimating the length of the first antiretroviral therapy regiment durability in Säo Paulo, Brazil

Brazil was the first country to provide unrestricted, cost-free access to antiretroviral (ARV) medicine for AIDS treatment. However, there is little data about the benefits of such a policy for these patients. We evaluated the duration of benefit obtained with the introduction of ARVs, defined as the durability of the first ARV regiment. We reviewed the medical charts of patients attended from 1996-2000, at the outpatient clinics of the Federal University of Säo Paulo, Brazil. A total of 120 drug-naive HIV-1 infected patients were eligible to participate in the study. About half of the individuals (53 percent) presented with disease symptoms; 59 percent of them had CD4 count below 200 cells/mm³. Mean estimated duration of the benefit of therapy was 14.1 months. The most used regimen in this cohort was Zidovudine/3TC/Indinavir (26 percent), followed by Zidovudine/DDI (17 percent), and Zidovudine/3TC/Nelfinavir (13 percent). The most frequent cause of interruption of therapy was gastrointestinal intolerance. Use of treatment regimens with three drugs was more effective than with two drugs, but only for patients with CD4<200 cells/mm³ or CV>100,000 copies RNA/mL. However, the use of triple therapy was associated with a significantly higher probability of reaching maximum viral suppression, during a longer period (p<0.05).The patients enrolled in the study benefitted from therapy for a limited time, after the introduction of double or triple antiretroviral therapy. The incidence of adverse events was significantly associated with loss of the benefits provided by the initial therapeutic regimen.

Compromiso neurológico en pacientes VIH: descripción y análisis con parámetros de uso frecuente / Neurological manifestations in HIV patients: description and analysis with frequently used parameters

Se analizó el compromiso neurológico primario en la población VIH(+) en control en el Hospital San Juan de Dios y la Fundación Arriarán, relacionando la presencia de alteraciones al examen neurológico con parámetros usados en el control de esta enfermedad: niveles de CD4, clasificación CDC, tiempo de evolución y tratamiento con zidovudina. Se estudió una muestra seleccionada de 48 pacientes VIH(+), en distintas etapas de la enfermedad, a los que se les práctico un examen neurológico completo. Los datos fueron analizados estadísticamente mediante una prueba de asociación (Chi cuadrado). el 57,4 por ciento de los pacientes presentaba alteraciones al examen neurológico. Estos representaban un 45 por ciento de los pacientes con niveles de linfocitos CD4 mayor a 500, entre 499 y 201 linfocitos y un 91 por ciento en pacientes con niveles de linfocitos CD4 menores a 200. Por último, se analizó la relación que existe entre la presencia de alteraciones neurológicas y la clasificación CDC. En etapa SIDA, se evidenció un 86& de pacientes con trastornos al examen neurológico. Los que no clasificaban como SIDA, sólo un 35 por ciento presentaron compromiso neurológico. Ambas diferencias fueron estadísticamente significativas. Los valores observados en relación a tiempo de evolución y tratamiento con zidovudina no fueron estadísticamente significativos. Para un diagnóstico precoz, el Minimental test fue el examen que evidenció mayor número de alteraciones

Zidovudine and interferon therapy for adult T-cell leukaemia/lymphoma: results of a preliminary study at UHWI-Mona

Seven patients with adult T-cell leukaemia/lymphoma(ATL) were treated with a combination of zidovudine (AZT) and interferon after failed chemotherapy. One patient showed a major response for nine months. The remainder showed progressive disease further complicated by drug toxicity. The poor responses could be explained by patient selection, since most patients had advanced disease refractory to chemotherapy. A larger more protracted study is required for further evaluation of this treatment option.

Hiperpigmentación cutáneo-mucosa en pacientes HIV positivos / Muco-cutaneous hyperpigmentation in HIV patients

Las alteraciones en la pigmentación cutáneo-mucosa en los pacientes infectados por el virus HIV pueden ser frecuentes, pero su etiología está aún en discusión. Se analizó el seguimiento dermatológico desde 1988 hasta 1995 de 320 casos infectados por el virus del HIV, donde 61 eran mujeres y 259 varones, cuyas edades promedio fueron de 26,6 años en los primeros y 22,2 en los segundos. Del total de casos (320), se observó hiperpigmentación cutáneo-mucosa difusa en el 16,32 por ciento de los casos e hiperpigmentación de mucosa y semimucosa oral exclusivamente en 2 mujeres (0,77 por ciento) y 12 varones (4,18 por ciento). En nuestra experiencia, la hiperpigmentación se comportó como un marcador de mal pronóstico, dado que en menos de 6 meses de su aparición, los pacientes presentaron complicaciones más severas que los llevaron a la muerte

AZT: farmacologia, benefícios e aplicaçÆes clínicas / AZT: pharmacology, general considerations and clinical effects

Este trabalho consiste numa revisåo dos principais tópicos referentes ao uso do AZT, como histórico, consideraçÆes gerais, mecanismo de açåo, farmacocinética, uso terapêutico e efeitos clínicos, reaçÆes adversas e interaçÆes medicamentosas. Pretender uma introduçåo para a descriçåo de nossa experiência com a droga, através de dois grupos de pacientes, 40 no total, a ser publicada num futuro próximo

Estudio fase II de la administración secuencial de zidovudina (AZT), zalcitabina (ddC) y didanosina (ddI) a pacientes con infección avanzada por el virus de la inmunodeficiencia humana tipo 1 (VIH-1) / Study of administration consecutive periods of zidorudine (AZT), zalcitabine (ddC) and didanosine (ddI) infected individuals by HIV-1

Se estudiaron prospectivamente 18 pacientes infectados por VIH-1 y tratados con AZT (100 mg. tid durante 30 días), alternando con ddC (0.375 mg. tid durante 30 días) y con ddl (100 mg. tid durante 30 días) por periódos de 12 a 28 semanas, media 20. Doce pacientes recibieron este tratamiento después de otros antirretrovirales y 6 lo recibieron desde el diagnóstico. Antes y después de AZT/ddC/ddI, la media de células CD4 cambió de 211 a 256/ul (p=.06), y la media de peso de 68.2 a 67.4 kg. (p=.05). Las cifras de hemoglobina se incrementaron significativamente de 14.8 a 15.4 gr/dl (p=.02); este efecto fue más notable en pacientes previamente expuestos a AZT. En 6 de 12 casos desapareció la antigenemia p24 y en 2 de 5 disminuyeron los niveles de beta2-microglobulina sérica. En ningún paciente hubo hiperamilasemia como efecto adverso del ddl y en uno se instaló neuropatía periférica sensorial reversible como efecto colateral de ddC; en seis que habían recibido AZT cesaron los efectos adversos como intolerancia gástrica, cefalea y fiebre. La administración combinada secuencial de AZT/ddC/ddl fue bien tolerada y disminuyó la toxicidad de AZT

Farmacología de las drogas empleadas en el tratamiento del SIDA / Pharmacology of the drugs employee in the treatment of AIDS

En esta revisión (transcripción de la presentación realizada en el Simposio SIDA, Avellaneda 1990) se enumeran las drogas empleadas para: 1)tratar las complicaciones del SIDA (solo algunos ejemplos, incluyendo foscarnet y glanciclovir); 2)realizar la inmunoterapia del SIDA; y 3)inhibir la replicación del HIV (quimioterápicos anti-HIV). En la segunda clase se enfatiza la necesidad de actuar precozmente (por ej., con valores no muy bajos de CD4), y se analizan evidencias preliminares sobre isoprinosina, timopentina y ditiocarb. En la tercera se analiza en detalle el mecanismo de acción de los dideoxinucleósidos, ejemplificando con la zidovudina, sus efectos adversos, sus limitaciones, en particular para tratamiento precoz, y el desarrrollo de resistencia en el HIV tanto in vitro como in vivo. Se analiza, también, el efecto del interferón * sobre la replicación viral y se esbozan los tratamientos más experimentales en farmacología clínica como el CD4 recombinante soluble) e in vitro (como los oligonucleótidos antisense). Pese a disponer de drogas efectivas en cada una de las tres categorías enunciadas, ninguna hace más que retrasar el curso de la infección hacia la destrucción del sistema inmune y muerte del paciente