Antiretroviral Therapy In HIV-infected Individuals Research Articles

Birth Country Influences the Choice of Antiretroviral Therapy in HIV-Infected Individuals: Experience From a French HIV Centre.

To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs). Observational single-center study. We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions. A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65). Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored.

A therapeutic vaccine strategy to prevent Pneumocystis pneumonia in an immunocompromised host in a non-human primate model of HIV and Pneumocystis co-infection.

Pneumocystis is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to Pneumocystis. Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti-Pneumocystis immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help. In the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti-Pneumocystis humoral immunity following virus-induced immunosuppression. Immunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti-Pneumocystis humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti-Pneumocystis immune responses during SIV-infection and contributed to protection against Pneumocystis co-infection in KEX1-vaccinated macaques. These studies present a novel strategy for stimulating durable anti-Pneumocystis humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.

Performance Evaluation of BD FACSPrestoTM Near-Patient CD4 Counter for Monitoring Antiretroviral Therapy in HIV-Infected Individuals in Primary Healthcare Clinics in Thailand.

HIV viral load is more reliable tool for monitoring treatment throughout the course of HIV/AIDS, but the test may be expensive in resource-limited settings. Therefore, enumeration of CD4 T-lymphocyte count remains important in these settings. This study evaluated the performance of BDFACSPresto, a near-patient CD4 counter planned to be used in primary healthcare clinics in Thailand. Results of percent, absolute CD4 count and hemoglobin (Hb) on the FACSPresto were compared with the TriTEST/TruCOUNT/BDFACSCalibur method and a Sysmex hematology analyzer. Phase I of the study was performed in an ISO15189 laboratory. Both percentage and absolute values showed Passing–Bablok slopes within 0.98–1.06 and 0.97–1.13, mean Bland–Altman biases of +1.2% and +20.5 cells/µL, respectively. In phase II, venous and some capillary blood samples were analyzed in four primary healthcare clinics. The results showed good correlation between capillary and venous blood. For venous blood samples, regression lines showed slopes of 1.01–1.05 and 1.01–1.07 for all percentage and absolute values. The overall mean biases were +0.9% and +17.0 cells/µL. For Hb, Passing–Bablok regression result gave slope within 1.01–1.07 and mean bias of −0.06 g/dL. Thus, CD4 enumeration in blood by the FACSPresto is reliable and can be performed to an identical standard at primary healthcare clinics.

Oral Microbiota Is Associated With Immune Recovery in Human Immunodeficiency Virus-Infected Individuals.

The role of the oral microbiota in HIV-infected individuals deserves attention as either HIV infection or antiretroviral therapy (ART) may have effect on the diversity and the composition of the oral microbiome. However, few studies have addressed the oral microbiota and its interplay with different immune responses to ART in HIV-infected individuals. Salivary microbiota and immune activation were studied in 30 HIV-infected immunological responders (IR) and 34 immunological non-responders (INR) (≥500 and < 200 CD4 + T-cell counts/μl after 2 years of HIV-1 viral suppression, respectively) with no comorbidities. Metagenome sequencing revealed that the IR and the INR group presented similar salivary bacterial richness and diversity. The INR group presented a significantly higher abundance of genus Selenomonas_4, while the IR group manifested higher abundances of Candidatus_Saccharimonas and norank_p_Saccharimonas. Candidatus_Saccharimonas and norank_p_Saccharimonas were positively correlated with the current CD4 + T-cells. Candidatus_Saccharimonas was positively correlated with the markers of adaptive immunity CD4 + CD57 + T-cells, while negative correlation was found between norank _p_Saccharimonas and the CD8 + CD38 + T-cells as well as the CD4/CD8 + HLADR + CD38 + T-cells. The conclusions are that the overall salivary microbiota structure was similar in the immunological responders and immunological non-responders, while there were some taxonomic differences in the salivary bacterial composition. Selenomona_4, Candidatus_Saccharimonas, and norank _p_Saccharimonas might act as important factors of the immune recovery in the immunodeficiency patients, and Candidatus_Saccharimonas could be considered in the future as screening biomarkers for the immune responses in the HIV-infected individuals.

Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells

People living with HIV (PLWH) are at increased risk for developing skin and mucosal malignancies despite systemic reconstitution of CD4+ Tcells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-related immunodeficiency in HIV is unclear. We found that skin CD4+ tissue-resident memory T (Trm) cells were depleted after HIV infection and replenished only upon early ART initiation. TCR clonal analysis following early ART suggested a systemic origin for reconstituting CD4+ Trm cells. Single-cell RNA sequencing in PLWH that received late ART treatment revealed a loss of CXCR3+ Trm cells and a tolerogenic skin immune environment. Human papilloma virus-induced precancerous lesion biopsies showed reduced CXCR3+ Trm cell frequencies in the mucosa in PLWH versus HIV- individuals. These results reveal an irreversible loss of CXCR3+ Trm cells confined to skin and mucosa in PLWH who received late ART treatment, which may be a precipitating factor in the development of HPV-related cancer.

A link between IL-23 and anti-CD4 autoantibody production in antiretroviral-treated HIV-infected individuals.

Potential mechanisms of poor CD4+ T cell reconstitution after viral suppression with antiretroviral therapy (ART) in HIV disease have been extensively investigated. We recently discovered that anti-CD4 autoantibody plays a role in impaired CD4+ T cell recovery from ART in HIV-infected individuals with viral suppression, which accounts for a mechanism specific for CD4+ T cell depletion. However, the mechanism of pathologic anti-CD4 autoantibody production in treated HIV disease remains unknown. Here we report that seasonal influenza vaccination induced IgG anti-CD4 autoantibodies, predominant IgG3 subclass, in some viral-suppressed ART-treated HIV+ subjects. To explore the mechanism of anti-CD4 antibody production in this population, we performed and analyzed gene profiles in isolated B cells using a gene microarray and plasma 32 cytokines. Notably, both gene expression and multiple cytokine analyses showed pre-vaccination plasma level of IL-23 was the key cytokine linked to IgG anti-CD4 antibody production in response to immunization in vivo Exogenous rIL-23 increased autoreactive IgG binding on CD4+ T cells from HIV+ subjects in vitro Results from this study may reveal a role of IL-23 in anti-CD4 autoantibody production in treated HIV.IMPORTANCEIn our published studies, we determine that pathological anti-CD4 IgGs from immunologic non-responders on virally-suppressive ART (CD4 cell counts < 350 cells/μL) mediated CD4+ T cell death via antibody-mediated cytotoxicity (ADCC), which play a role in poor CD4+ T cell recovery from ART. Up to 25% of HIV-infected individuals are non-responders and demonstrate increased morbidity and mortality. However, the mechanism of anti-CD4 autoantibody production in treated HIV remains unknown. In this study, we report that IL-23 may be the key cytokine to promote anti-CD4 autoantibody production after immunization in ART-treated HIV-infected individuals.

ТУБЕРКУЛЕЗ КАК РЕЗУЛЬТАТ СИНДРОМА ВОССТАНОВЕНИЯ ИММУННОЙ СИСТЕМЫ ПОСЛЕ НАЧАЛА АНТИРЕТРОВИРУСНОЙ ТЕРАПИИ

Начало антиретровирусной терапии у ВИЧ-инфицированных лиц несет в себе высокий риск развития синдрома восстановления иммунной системы с проявлением ранее не диагностированных инфекций, в том числе туберкулеза.Целью исследования было оценить клинико-рентгенологические особенности и эффективность лечения туберкулеза, развившегося в результате СВИС после начала АРТ у ВИЧ-инфицированных пациентов. Материал и методы. Изучены 24 медицинские карты стационарных больных ко-инфекцией туберкулез/ВИЧ, находившихся на лечении в Республиканской клинической туберкулезной больнице г. Донецка, у которых туберкулез развился в течение первых трех месяцев после начала антиретровирусной терапии. На догоспитальном этапе всем пациентам перед началом противовирусного лечения проводили объективный осмотр, рентгенографию органов грудной клетки, определяли содержание CD4-лимоцитов крови. Результаты и обсуждение. Перед началом антиретровирусной терапии медианы содержания CD4 в крови пациентов составляли 35 кл/мкл и 4,7%, не имели жалоб 7 человек (29,2%)%, 13 (54,2%) отмечали повышение температуры тела, 12 (50,0%) – слабость, 8 (33,3%) – кашель с мокротой, 4 (16,7%) – снижение массы тела, и у 2 лиц (8,3%) имелась неврологическая симптоматика. Рентгенологически нормальная картина органов грудной клетки определялась у 11 больных (45,8%), у 13 (54,2%) имелось усиление легочного рисунка, у 6 (25,0%) – увеличение внутригрудных лимфатических узлов. Первые симптомы туберкулеза появлялись в сроки от 3 до 60 дней, медиана – 19 дней, все больные отмечали лихорадку и слабость, у 9 (37,5%) наблюдались признаки туберкулезного менингита, у 17 (70,8%) – генерализованного туберкулеза. За стационарный период лечения умерло 14 человек (58,3%). Из 9 больных туберкулезным менингитом погибло семеро (77,8%). Успешно закончили стационарный этап противотуберкулезной химиотерапии и были выписаны для продолжения лечения в амбулаторных условиях 8 человек (33,3%). Выводы. Туберкулез, развивающийся в результате синдрома восстановления иммунной системы, возникает у ВИЧ-инфицированных лиц с глубокой иммуносупрессией при назначении антиретровирусной терапии без антимикобактериальных препаратов, характеризуется быстрым развитием, склонностью к генерализации и неблагоприятным прогнозом. Особо злокачественным течением отличается туберкулезный менингит, при котором летальность достигает 77,8%. У 54,2% больных перед началом противовирусного лечения отмечались лихорадка, у такого же количества – усиление легочного рисунка, у 25,0% – увеличение внутригрудных лимфатических узлов. Наличие указанных симптомов является основанием для отсрочки антиретровирусной терапии и детального обследования пациентов. При невозможности верифицировать причину патологии целесообразно начинать противовирусное лечение под прикрытием противотуберкулезной химиотерапии, однако ее схема и продолжительность нуждаются в четкой регламентации.

Treatment Engagement Moderates the Effect of Neurocognitive Impairment on Antiretroviral Therapy Adherence in HIV-Infected Drug Users in Treatment

Neurocognitive impairment (NCI) and treatment engagement (TE) have been shown to significantly predict antiretroviral therapy (ART) adherence, but no studies have explored the ways and the extent to which similar outcomes might occur when these factors operate together, particularly for people who use drugs (PWUDs). We sought to discover whether TE moderated the effect of NCI on adherence to ART in HIV-infected individuals. One hundred sixteen HIV-infected, methadone-maintained people who reported HIV risk behaviors were enrolled in the study. Variables of interest (NCI, ART adherence, TE) were assessed using audio computer-assisted self-interview. Results revealed a significant interactive effect of NCI and TE on ART adherence, which supported the moderation effect. Findings from post hoc analyses showed that NCI was negatively associated with adherence to ART at low levels of TE. Findings suggest the need to accommodate individual NCI and improve TE as a means to enhance ART adherence in HIV-infected PWUDs.

Review: [corrected] The changing face of the HIV epidemic in sub-Saharan Africa.

The widespread roll-out of antiretroviral therapy (ART) has substantially changed the face of human immunodeficiency virus (HIV). Timely initiation of ART in HIV-infected individuals dramatically reduces mortality and improves employment rates to levels prior to HIV infection. Recent findings from several studies have shown that ART reduces HIV transmission risk even with modest ART coverage of the HIV-infected population and imperfect ART adherence. While condoms are highly effective in the prevention of HIV acquisition, they are compromised by low and inconsistent usage; male medical circumcision substantially reduces HIV transmission but uptake remains relatively low; ART during pregnancy, delivery and breastfeeding can virtually eliminate mother-to-child transmission but implementation is challenging, especially in resource-limited settings. The current HIV prevention recommendations focus on a combination of preventions approach, including ART as treatment or pre- or post-exposure prophylaxis together with condoms, circumcision and sexual behaviour modification. Improved survival in HIV-infected individuals and reduced HIV transmission risk is beginning to result in limited HIV incidence decline at population level and substantial increases in HIV prevalence. However, achievements in HIV treatment and prevention are threatened by the challenges of lifelong adherence to preventive and therapeutic methods and by the ageing of the HIV-infected cohorts potentially complicating HIV management. Although current thinking suggests prevention of HIV transmission through early detection of infection immediately followed by ART could eventually result in elimination of the HIV epidemic, controversies remain as to whether we can treat our way out of the HIV epidemic.

Absolute lymphocyte count is not a suitable alternative to CD4 count for determining initiation of antiretroviral therapy in fiji.

Introduction. An absolute lymphocyte count is commonly used as an alternative to a CD4 count to determine initiation of antiretroviral therapy for HIV-infected individuals in Fiji when a CD4 count is unavailable. Methods. We conducted a retrospective analysis of laboratory results of HIV-infected individuals registered at all HIV clinics in Fiji. Results. Paired absolute lymphocyte and CD4 counts were available for 101 HIV-infected individuals, and 96% had a CD4 count of ≤500 cells/mm3. Correlation between the counts in individuals was poor (Spearman rank correlation r = 0.5). No absolute lymphocyte count could be determined in this population as a suitable surrogate for a CD4 count of either 350 cells/mm3 or 500 cells/mm3. The currently used absolute lymphocyte count of ≤2300 cells/μL had a positive predictive value of 87% but a negative predictive value of only 17% for a CD4 of ≤350 cells/mm3 and if used as a surrogate for a CD4 of ≤500 cells/mm3 it would result in all HIV-infected individuals receiving ART including those not yet eligible. Weight, CD4 count, and absolute lymphocyte count increased significantly at 3 months following ART initiation. Conclusions. Our findings do not support the use of absolute lymphocyte count to determine antiretroviral therapy initiation in Fiji.

Directly administered antiretroviral therapy for HIV-infected individuals in opioid treatment programs: results from a randomized clinical trial.

BackgroundData regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.MethodsHIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.ResultsWe randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.ConclusionsIn this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.Trial RegistrationClinicalTrails.gov NCT00279110 NCT00279110?term = NCT00279110&rank = 1

Impact of immunodepression and moderate alcohol consumption on coronary and other arterial disease events in an 11-year cohort of HIV-infected patients on antiretroviral therapy

ObjectiveTo investigate the relationship between response to antiretroviral therapy (ART), alcohol use and occurrence of a major coronary or other arterial disease event (CADE) in HIV-infected individuals.DesignA cohort study. A...

Early antiretroviral therapy: the role of cohorts

To review the data that contribute to the debate on the optimal time to initiate highly active antiretroviral therapy in HIV-infected individuals, with a focus on the information that is available from cohort studies. The findings from cohort studies generally support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl. In particular, the findings that death rates among treated HIV-infected individuals are higher than those in the general population, and that the risks of AIDS and serious non-AIDS events are higher in those with lower CD4 cell counts (even when the count remains >350 cells/microl), suggest that earlier initiation of highly active antiretroviral therapy may prevent some excess morbidity and mortality. However, given the lack of adjustment for lead-time bias in many analyses, the potential for residual confounding and the possible incomplete ascertainment of relevant outcomes in cohorts, it cannot be concluded that the benefits of highly active antiretroviral therapy when started at higher CD4 cell counts will outweigh the possible detrimental effects. Whereas the data from cohort studies currently support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl, there is an urgent need for data from randomized trials to inform this decision.

Pathogenesis of HIV-HCV coinfection

Hepatitis C virus (HCV) and HIV-1 are often harbored in the same host, establishing chronic infections typically characterized by persistent viremia. HIV-1 has deleterious effects on the course of HCV infection by increasing the rate of HCV viral persistence, quantitative HCV RNA levels, and ultimately the liver fibrosis progression rate. Conversely, HCV may blunt the effectiveness of immune reconstitution following antiretroviral therapy in HIV-infected individuals. Better understanding of the pathogenic mechanisms underlying these clinical observations may facilitate novel and effective therapeutic interventions that tackle the clinical conundrums raised by HIV/HCV coinfection.

Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naive individuals and those treated in the monotherapy era.

One key piece of information required when deciding whether to initiate antiretroviral therapy is the risk of AIDS before the next clinic visit. Information on the short-term (6-month) risk of AIDS according to the current viral load and CD4 cell count in untreated individuals and those treated in the zidovudine monotherapy era (i.e., pre-September 1995), especially in those with CD4 cell count > 200 x 10 cells/l, is lacking. Risk of AIDS was assessed in 3226 subjects with viral load and CD4 cell count known before initiation of antiretroviral therapy or during the zidovudine monotherapy era. These were from CASCADE Collaboration in which data from 20 cohorts of individuals with known dates of seroconversion to HIV, based in clinics in Europe and Australia, have been combined. During a total 5126.0 person-years of follow-up, 219 individuals developed AIDS. In those with current CD4 cell count < 200 x 10 cells/l, 6-month risks were 4.9, 12.7, 17.7 and 22.4% for viral load groups < 10 000, 10 000-29 999, 30 000- 99 999 and > or = 100 000 copies/ml, respectively. For CD4 cell counts 200-349 x 10 cells/l risks were 0.5, 1.6, 3.2 and 4.7%, respectively, for the four viral load groups while the corresponding values for group with CD4 cell count > or = 350 x 10 cells/l were 0.2%, 0.5%, 0.9% and 2.2%, respectively. Results were similar when analysis was restricted to those with no antiretroviral drug experience. Older people had a higher risk of AIDS for a given CD4 cell count and viral load than younger people. Combined with consideration of other issues, these estimates should prove useful information when deciding whether to initiate antiretroviral therapy in HIV-infected individuals.

Antiretroviral therapy in HIV-infected individuals in clinical practice: are the criteria for initiating and choosing the type of drug regimen based only on immunologic and virologic values?

To determine factors associated with beginning antiretroviral therapy and with the number of drugs used. Longitudinal study of 3169 HIV-infected individuals naïve from antiretroviral drugs at enrollment in 65 infectious disease clinics in Italy. Initiation of antiretroviral therapy and number of drugs used (i.e., < 3 vs. > or = 3 drugs) were the main outcome measures. Adjusted odds ratios were calculated by logistic models to establish cofactors of these two measures. From January 1997 to December 1998, 1288 (40.6%) individuals started therapy, 58.0% of whom were given a triple combination regimen. This regimen became more frequent over time. By multivariate analysis, high levels of HIV-RNA and low CD4 counts were the most important independent predictors of starting any type of therapy. A significant association was also found with HIV exposure category, reason for being antiretroviral-naïve, presence/absence of liver disease, presence/absence of a new AIDS-defining disease, and clinical centre. High levels of HIV-RNA and low CD4 counts were also the most important predictors of starting with > or = 3 drugs, compared to < 3 drugs, and men had an independent higher probability of starting with > or = 3 drugs, compared to women. The probability of starting with > or = 3 drugs significantly increased with calendar time. CD4 and HIV-RNA were the main cofactors of initiating both any type of therapy and therapy with > or = 3 drugs. The large variability among clinical centres suggests that clinicians are uncertain as to the exact timing of beginning therapy and the specific regimen, especially among women.

An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay.

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.