Protease Inhibitor-based Highly Active Antiretroviral Therapy Research Articles

Impact of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Fetal Subcutaneous Fat Tissue in HIV-Pregnant Women in a Middle-Income Country.

HIV infection continues to be a global public health challenge, affecting approximately 1.7 million reproductive-aged women. Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has significantly reduced the risk of vertical transmission of HIV from mother to child. Nevertheless, concerns linger regarding the long-term effects, particularly on body composition, notably subcutaneous fat tissue (SFT). Although HIV-associated lipodystrophy syndrome (LS) has been well documented in adults and older children, its impact on fetuses exposed to PI-HAART remains underexplored. This study aims to evaluate SFT in the fetuses of HIV-pregnant women exposed to PI-HAART, assessing the potential clinical implications. We conducted a comparative study between HIV-pregnant women receiving PI-HAART and an HIV-negative control group. Fetometry measurements were obtained via 3D ultrasound. SFT in the fetal arm and thigh segments was assessed. Data were analyzed using lineal multivariate regression and receiver-operating characteristics (ROC)-curve analysis. Fetuses exposed to PI-HAART exhibited a significant reduction in subcutaneous fat, particularly in the proximal third-middle union of the femur (coefficient: -2.588, p = 0.042). This reduction was correlated with lower newborn serum glucose levels (65.7 vs. 56.1, p = 0.007; coefficient: -1.277, p = 0.045). Our study sheds light on the connection between PI-HAART, fetal subcutaneous fat, and neonatal health. These findings might reveal the long-lasting effects of PI-HAART on newborns and children's well-being. Our results emphasize the need for a more balanced approach to managing pregnant women with HIV in developing countries and open new venues for research on the impact of intrauterine PI-HAART exposure on energy metabolism and fetal programming.

Duration and reasons for changing the first antiretroviral therapy: an 8-year follow-up

BackgroundFailure of first highly active antiretroviral therapy (HAART) reduces both the duration and the chances of viral control in subsequent regimens, due to cross-resistance and common toxicity between and within...

Clinical outcomes of HIV‐infected patients with Kaposi's sarcoma receiving nonnucleoside reverse transcriptase inhibitor‐based antiretroviral therapy in Uganda

Clinical outcomes for patients with Kaposi's sarcoma (KS) using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) in resource-limited settings have not previously been described. We evaluated HIV-infected patients aged ≥ 18 years, who initiated HAART in the Home-Based AIDS Care (HBAC) project in Tororo, Uganda, between May 2003 and February 2008 and were diagnosed with KS at baseline or during follow-up. We examined independent risk factors for having either prevalent or incident KS and risk factors for death among patients with KS. Of 1121 study subjects, 17 (1.5%) were diagnosed with prevalent KS and 18 (1.6%) with incident KS over a median of 56.1 months of follow-up. KS was associated with male sex [adjusted odds ratio (AOR) 2.41; 95% confidence interval (CI) 1.20-4.86] and baseline CD4 cell count < 50 cells/μL (AOR 3.25; 95% CI 1.03-10.3). Eleven (65%) of 17 patients with prevalent KS and 13 (72%) of 18 patients with incident KS experienced complete regression (P = 0.137). Eighteen (64%) of 28 patients who remained on NNRTI-based HAART experienced regression of their KS and six (86%) of seven patients who were switched to protease inhibitor-containing HAART regimens had regression of their KS (P = 0.23). Mortality among those with KS was significantly associated with visceral disease (hazard ratio 19.22; 95% CI 2.42-152). Prevalent or incident KS was associated with 30% mortality. The resolution of KS lesions among individuals who initiated HAART with NNRTI-based regimens was similar to that found in studies using only protease inhibitor-based HAART.

Mother‐to‐Child Transmission of HIV‐2 Infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF‐CO1

Management of pregnant women with human immunodeficiency virus (HIV) type 2 infection remains unclear because of its low prevalence and important differences from HIV-1. Pregnant women monoinfected with HIV-2 or HIV-1 and their infants enrolled in the prospective, national, multicenter French Perinatal Cohort between 1986 and 2007. Overall, 2.6% (223/8660) of mothers were infected with HIV-2, and they accounted for 3.1% (367/ 11841) of the total births. Most were born in sub-Saharan Africa. A higher proportion of HIV-2-infected mothers than HIV-1-infected mothers had no symptoms, had received no antiretroviral therapy at conception (85.9% vs 66.7%), and had received no antiretroviral therapy during pregnancy (42.8% vs 19.9%), particularly highly active antiretroviral therapy (HAART) (79.7% vs 46.1%), and they had higher CD4 cell counts near delivery (median, 574 vs 452 cells/mm3; P < .01). If antiretroviral therapy was used, it was started at a later gestational age for HIV- 2-infected mothers (median, 28 vs 25 weeks; P < .01). HIV-2-infected mothers were more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs 0.6%; P < .01), and their infants less frequently received postexposure prophylaxis. In the period 2000-2007, the proportion with viral load <100 copies/mL at delivery was 90.5% of HIV-2-infected mothers, compared with 76.2% of HIV-1-infected mothers (P=.1). There were 2 cases of transmission: 1 case in 1993 occurred following maternal primary infection, and the other case occurred postnatally in 2002 and involved a mother with severe immune deficiency. The mother-to-child transmission rate for HIV-2 was 0.6% (95% confidence interval, 0.07%-2.2%). Care for HIV-2-infected pregnant women rests on expert opinion. The mother-to-child transmission residual rate (0.07%-2.2%) argues for systematic treatment: protease inhibitor-based HAART for women requiring antiretrov

Successful Immunologic and Virologic Outcomes in Elderly HIV-Infected Patients

Successful Immunologic and Virologic Outcomes in Elderly HIV-Infected Patients

Metabolic bone disease in HIV infection

HIV mainly replicates in CD4þ T lymphocytes andmonocyte/macrophages causing severe immunologicalimpairment. In addition to the immune system, HIVinfection affects tissues and organs such as kidney, liver,the central nervous system, heart and bone showing acomplex pathogenesis [1].The advent and widespread use of highly activeantiretroviral therapy (HAART) in the last two decadeshasled toa markedimprovementinthe treatmentofHIVdisease even though viral infection cannot be eradicatedbecause HAART does not completely eliminate the viralreservoirs [2]. HAART has dramatically changed thecourseofHIVinfection froma fatalinfectiontoachronicand relatively manageable disease. The increased lifeexpectancyofHIVpatientsandtheeffectsofHAARThavechanged the management of HIV infection. Nowadaysmedical treatment is no longer focused solely on HIVinfection, opportunistic diseases and monitoring immunederangement, but also includes the control of metabolic,cardiovascular, liver, bone and kidney complications. Inparticular, bone alterations have been observed in thecourse of HIV disease representing a pivotal clinicalprobleminthemanagementofHIVpatientsespeciallyforapossible development of bone fractures [3]. The majorbonelesionsdetectableinHIVpatientsarerelatedtobonedemineralization (osteopenia/osteoporosis and osteoma-lacia) and osteonecrosis ([4] for a review).This report will discuss the pathogenesis, diagnosis andtreatment of major bone complications represented bybone demineralization diseases during HIV infection andHAART treatment.

Association of Single‐Nucleotide Polymorphism 3 and c.553G&gt;T ofAPOA5with Hypertriglyceridemia after Treatment with Highly Active Antiretroviral Therapy Containing Protease Inhibitors in HIV‐Infected Individuals in Taiwan

We investigated the relationship between hypertriglyceridemia and the single-nucleotide polymorphisms (SNPs) on APOA5 in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) in Taiwan. Receipt of protease inhibitor-based HAART, high baseline triglyceride levels, and carriage of APOA5 SNP3 or c.553G>T variants or APOA5 SNP1T/SNP2G/SNP3C/c.553T haplotype were statistically significantly associated with development of extreme hypertriglyceridemia (triglyceride level, >500 mg/dL).

Lipid‐Lowering Efficacy and Safety After Switching to Atazanavir‐Ritonavir‐Based Highly Active Antiretroviral Therapy in Patients with Human Immunodeficiency Virus

To evaluate the efficacy, safety, and lipid-lowering effects after switching from a non-atazanavir-containing, protease inhibitor-based highly active antiretroviral therapy (HAART) to atazanavir-ritonavir-based HAART in patients infected with human immunodeficiency virus (HIV). Multicenter, noncontrolled, retrospective study. Three tertiary teaching hospitals. Thirty-six patients with HIV infection, aged 18 years or older, who were receiving non-atazanavir-containing, protease inhibitor-based HAART that was switched to atazanavir 300 mg-ritonavir 100 mg-based HAART without changes in nucleoside reverse transcriptase inhibitors and confounders known to alter serum lipid levels. Lipid profiles measured 4 weeks-6 months before the switch, as well as follow-up lipid profiles measured 4 weeks-6 months after receiving the new HAART regimen, were evaluated. The switch resulted in the following changes in lipid levels: total cholesterol -9% (p=0.002), low-density lipoprotein cholesterol -13% (p<0.001), high-density lipoprotein cholesterol (HDL) -2% (p=0.431), triglycerides -23% (p=0.007), non-HDL -11% (p=0.002), total cholesterol:HDL ratio -10% (p=0.004), and triglyceride:HDL ratio -24% (p=0.019). A subgroup analysis was conducted on the lipid profiles of nine patients who still met the strict inclusion and exclusion criteria up to 9 months after the switch; it showed that the reductions in their lipid profiles were sustained. In addition, 33% more patients achieved their National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III cholesterol goals. No significant changes were noted in median (interquartile range) CD4+ counts (372 [236-551] and 361 [217-464] cells/mm(3), p=0.118) or in number of patients with undetectable HIV viral loads ([defined as < 50 copies/ml] 32/36 and 31/36 patients, p>0.05) between baseline and after the switch, respectively. Switching to an atazanavir-ritonavir-based HAART regimen was associated with significant improvement in lipid profiles, similar to those seen in clinical trials, without compromising safety or viral and immunologic control. In addition, more patients were able to achieve their NCEP ATP III goals.

Patterns, Predictors, and Consequences of Initial Regimen Type among HIV-Infected Women Receiving Highly Active Antiretroviral Therapy

It is important to elucidate differences among initial highly active antiretroviral therapy (HAART) regimen types in comparative studies of therapy effectiveness. We aimed to identify predictors of initiation with different HAART regimen types and the effect of initial regimen type on switching and immunologic response to therapy--controlling for those predictors--among human immunodeficiency virus (HIV)-infected women in the United States. Participants in the Women's Interagency HIV Study underwent semiannual interview, venipuncture, and clinical examination. Those beginning with protease inhibitor-based, nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based, or triple-nucleoside reverse-transcriptase inhibitor (NRTI)-based HAART during April 1996-March 2005 were eligible for analysis. Predictors of initial regimen type were assessed with polytomous logistic regression. Correlates of switching were assessed with discrete-time proportional hazards models, and immunologic response to therapy was assessed with linear regression. Among 1555 HAART initiators, CD4(+) lymphocyte count and HIV load were significant predictors of initial regimen type during 1996-2002; only sociodemographic predictors were significant during 2002-2005. Initial regimen type was not a significant predictor of subsequent regimen switching. Compared with those whose initial treatment was protease inhibitor-based HAART, those who began with triple-NRTI-based regimens had significantly lower CD4(+) cell counts at 1 year (P=.006) and 2 years (P=.004) after initiation; NNRTI initiators had lower CD4(+) cell counts after 2 years (P=.05). We demonstrate that predictors of initial regimen type among women in the United States have been changing over time. Protease inhibitor initiators had significantly higher CD4(+) cell counts than did NNRTI or triple-NRTI initiators up to 2 years after HAART initiation. Adjustment for biological predictors of initial regimen is important to avoid confounding in the study of treatment effectiveness.

Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women

Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income < $10,000 vs. > $40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

Residual viraemia in subjects with chronic HIV infection and viral load &lt; 50 copies/ml: the impact of highly active antiretroviral therapy

To determine factors associated with < 2.5 copies/ml plasma HIV RNA in subjects treated with highly active antiretroviral therapy (HAART) and with viraemia < 50 copies/ml. Cross-sectional analysis of 84 HIV-positive patients taking HAART with plasma HIV RNA < 50 copies/ml for at least 6 months and no history of virological failure. Current HAART therapy was based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 66%, a protease inhibitor in 26% and nucleoside reverse transcriptase inhibitors in 7%. Viraemia levels were measured using a modified ultrasensitive Roche Amplicor HIV-1 Monitor test able to quantify plasma HIV RNA to a lower limit of 2.5 copies /ml; proviral DNA was measured with a real-time polymerase chain reaction assay. Analysis of variance and multiple logistic regression analysis were utilized to test for associations between residual replication and other variables. Residual HIV viraemia > 2.5 copies/ml was found in 50% of subjects; 94% of subjects had detectable proviral DNA (>or= 20 copies/10(6) peripheral blood mononuclear cells) and 21% had archived mutations. Usage of a NNRTI-based HAART was the only independent predictor of viral suppression below the cut-off value of the modified ultrasensitive assay. In our population, NNRTI-based HAART seems to have a stronger impact on residual replication than protease inhibitor-based HAART. This finding may be considered in therapeutic decisions such as the choice of initial HAART regimen and the interruption or simplification of treatment.

CD4+ Cell Count, Viral Load, and Highly Active Antiretroviral Therapy Use Are Independent Predictors of Body Composition Alterations in HIV-Infected Adults: A Longitudinal Study

To understand the concurrent effects of human immunodeficiency virus (HIV) infection, the immune system, and antiretroviral therapy on body composition alterations, we examined annualized composition changes in HIV-infected adults who were receiving stable antiretroviral therapy. With use of data from the Nutrition For Healthy Living Study, we performed multivariate analyses using longitudinal models to evaluate the relationship of CD4+ cell count, viral load, and highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART) with changes in trunk and extremity composition for 110 men and 42 women who provided data relating to 194 study intervals (i.e., intervals of time between 2 assessment visits). Of these intervals, 165 involved HAART use (89.7% involved protease inhibitor-based regimens), and 29 did not involve HAART use. Patients receiving HAART or ART (who had continuous use during the interval) were compared with HAART- or ART-naive subjects. The median length of intervals between visits was 12.9 months (interquartile range, 12.1-17.6 months). In models adjusted for HAART or ART use, baseline CD4+ cell count was positively associated with increased trunk fat (mean increase per year, 2.3% per 100 cells/mm3; 95% confidence interval [CI], 0.7%-3.9%]) and, in men, with increased extremity fat (mean increase per year, 1.8% per 100 cells/mm3; 95% CI, 0.6%-3.0%). Increase in CD4+ cell count predicted increased extremity lean mass (mean increase per year, 0.6% per 100 cells/mm3; 95% CI, 0.05%-1.1%). Higher baseline viral load predicted fat loss (trunk fat loss per year, -5.0% per log10 copies/mL; 95% CI, -9.4% to -0.7%; extremity fat loss per year, -3.4% per log10 copies/mL; 95% CI, -6.1% to -0.6%), as did zidovudine use (trunk fat loss per year, -10.8%; 95% CI, -20.4% to -1.4%; extremity fat loss per year, -4.9%; 95% CI, -9.8% to -0.01%). HAART use independently predicted decreased bone mineral content (extremity bone mineral content loss per year, -1.6%; 95% CI, -3.1% to -0.08%) but did not predict changes in fat or lean mass. Receipt of protease inhibitor-based HAART predicted a -1.9% decrease in extremity bone mineral content per year (95% CI, -3.6% to -0.2%), and zidovudine use predicted a -2.6% decrease in trunk bone mineral content per year (95% CI, -4.4% to -0.8%). Baseline viral load, CD4+ cell count, and change in CD4+ cell count predicted alterations in trunk fat, extremity fat, and lean mass. HAART use and zidovudine use were associated with bone loss, and zidovudine use was associated with fat loss, but HAART use was not associated with fat mass changes.

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

Objective To study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk. Methods and design The lipid and HDL subpopulation profiles of HIV-positive subjects ( n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with ( n = 96) and without CHD ( n = 96). Results HIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns). Conclusion An already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.

An Extremely Different Dysmetabolic Profile Between the Two Available Nonnucleoside Reverse Transcriptase Inhibitors: Efavirenz and Nevirapine

An Extremely Different Dysmetabolic Profile Between the Two Available Nonnucleoside Reverse Transcriptase Inhibitors: Efavirenz and Nevirapine

Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV-infected individuals. However, the emergence of long-term side-effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV-infected patients on HAART. Ten HIV-infected patients on protease inhibitor-based HAART with hyperlipidaemia followed a cholesterol-lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol-lowering diet. Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild-type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and LDL-receptor expression. Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV-infected patients on HAART, potentially resulting in both hypolipidaemic and anti-inflammatory effects.

Advances in the pathobiology and treatment of Kaposi sarcoma.

Kaposi sarcoma, which has reached epidemic proportions in parts of Africa and in the Western world, continues to pose a problem in patients with AIDS receiving highly active antiretroviral therapy (HAART). This article reviews the new and important information regarding the epidemiology, biology, and management of Kaposi sarcoma that was published in the last year. Worldwide Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV8) seropositivity has been found to exceed the incidence of Kaposi sarcoma. Therefore, investigators have justifiably implicated other cofactors (eg, blood-sucking arthropods, angiotensin converting enzyme inhibitors, hemodialysis, and iron) in the development of Kaposi sarcoma. In the transplant setting, Kaposi sarcoma lesions have been shown to originate from the engraftment of donor tumor cells. The detection of HHV8 in Kaposi sarcoma lesions has provided a new diagnostic tool to help differentiate Kaposi sarcoma from its mimics. Kaposi sarcoma lesional cells, now confirmed to be of lymphatic origin, have been shown to express several chemokine receptors, some of which may help explain the predilection for skin. Regression of Kaposi sarcoma has been characterized histologically for the first time. The finding that some tumor cells can remain in an atrophic state even in completely regressed lesions suggests that they have the potential to recur. Protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based HAART regimens have been verified to be similarly effective. Although antiretrovirals have been noted to favorably alter the clinical characteristics of Kaposi sarcoma favorably, they seem not to alter the natural history of this disease. In the HAART era, because CD4 cell count was shown no longer to provide prognostic information about AIDS-related Kaposi sarcoma, the traditional classification system for staging AIDS-related Kaposi sarcoma has been refined. Also, a new staging system for classic Kaposi sarcoma has been proposed. Numerous advances have emerged regarding Kaposi sarcoma during the last year, many of which still need to be translated into clinically useful information. The results of new clinical trials involving antivirals purposely directed against HHV8 and antiretrovirals for HIV-uninfected people are anticipated. Finally, although investigators during this period did provide us with additional potential therapeutic targets, more novel approaches such as RNA interference and gene therapy have been also proposed as options in the future management of Kaposi sarcoma.

Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients.

To evaluate the durability and correlates of the effectiveness of highly active antiretroviral therapy (HAART) in terms of AIDS-related mortality and morbidity, HIV viremia, and CD4 cell count. The HIV Outpatient Study (HOPS), a prospective observational cohort from eight clinics in the USA that has been running since 1994. Mortality and opportunistic infection (OI) rates were calculated for 1769 HOPS patients with CD4 cell count ever < 100 x 106/l. Data from 1022 HAART recipients with CD4 cell count ever < 500 x 106/l were analyzed. Mortality and AIDS-related OI rates. Treatment success was defined as a reduction in plasma HIV RNA copies/ml of 1.0 log10 or more, or to an undetectable level, with a stable or rising CD4 cell count. Durable success was a successful response lasting at least 12 consecutive months. HAART use remained high; mortality and OIs low. Patients received a mean of 1.8 HAART regimens. Median time on first HAART (n = 1022) was 11.8 months; second HAART (n = 424) 7.4 months; and third HAART (n = 213) 7.2 months. Treatment success was most likely for pre-HAART treatment naive patients; durably successful first HAART most often contained one protease inhibitor, particularly indinavir or nelfinavir (P = 0.006, adjusted for prior antiretroviral therapy). Durable success was most likely with first (49.0%) than with second (29.6%, P = 0.013) or third or more HAART regimens (14.9%, P < 0.0001). Time to success with first HAART was shorter for durable than non-durable responders (3.6 versus 5.3 months, respectively; unadjusted P = 0.002). Durable response to HAART was associated with being pre-HAART therapy naive, prompt response to HAART, and single protease inhibitor-based initial HAART (indinavir or nelfinavir). Sequential HAART regimens were of progressively shorter duration, demonstrated less viral suppression and CD4 cell count benefit, yet low morbidity and mortality rates were sustained.