Use of viral load measured after 4 weeks of highly active antiretroviral therapy to predict virologic outcome at 24 weeks for HIV-1-positive individuals

Early prediction of suboptimal viral response to highly active antiretroviral therapy (HAART) is vital to prevent early development of drug resistance. We used logistic regression to predict the odds of achieving virologic suppression (<50 copies/mL) after 24 weeks of HAART in 656 antiretroviral-naive patients starting HAART at the J.W. Goethe University, Chelsea and Westminster, and Royal Free Hospitals according to their week 4 viral load. Therapy changes involving the switch of a single antiretroviral were assumed to have occurred for toxicity reasons and ignored. Because complete regimen changes or additions of new antiretrovirals could be due to virologic failure, patients were counted as virological failures at week 24. Three hundred sixty (84%) of 430 patients with viral loads of <1000 copies/mL, 106 (61%) of 175 with viral loads between 1001 and 10,000 copies/mL, 11 (37%) of 30 with viral loads between 10,001 and 100,000 copies/mL, and 5 (24%) of 21 with viral loads of >100,000 copies/mL at week 4 subsequently attained virologic suppression at 24 weeks. The odds of attaining virologic suppression at 24 weeks was 65% lower for every 1-log higher viral load at week 4 (odds ratio, 0.35; 95% confidence interval, 0.27-0.45). The proportion of patients with an undetectable viral load at 24 weeks among those who have not attained a viral load of <1000 copies/mL by 4 weeks is quite low. We suggest that this group of patients should be particularly closely monitored.     

Clinical, biologic, and behavioral predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors

Predictors of virologic (plasma HIV RNA viral load [VL] < 500 copies/ml) and immunologic (rise in CD4+ cell count > 50 cells/mm3) response after 4 months of therapy (M4) were studied in 750 HIV-1-infected patients prospectively enrolled at the initiation of a protease inhibitor (PI)-containing regimen. A virologic response was observed in 80% of patients, and an immunologic response was observed in 64%. Sixty-two percent of patients self-reported full adherence to therapy at 1 month of therapy (M1) and M4. In multivariate analysis, a virologic response was more frequent in fully adherent patients (odds ratio [OR] = 2.0; p =.001). An immunologic response was associated with age < 36 years (OR =1.4; p =.03), baseline VL (OR = 1.5 per 1 log10 copies/ml higher; p <.01), decrease in VL at M1 (OR = 1.5 per 1 log10 copies/ml decrease; p <.01), baseline total lymphocyte count (OR = 1.7 per 50% lower; p <.001), and baseline CD4+ cell percentage > or = 20% (OR =1.9; p <.001) but not with adherence to therapy. Full adherence seems to be a major predictor of a virologic response to PI-containing triple therapy. An immunologic response may be possible despite incomplete adherence, at least early in therapy.     

Baseline CD4(+) cell count, not viral load, correlates with virologic suppression induced by potent antiretroviral therapy.

OBJECTIVE: To investigate the relationship between viral load suppression and baseline viral load as well as that between viral load suppression and baseline CD4(+) cell count. DESIGN: Meta-analysis of published and presented studies. METHODS: Trials of two nucleoside analogs plus nevirapine, indinavir, nelfinavir, or efavirenz as therapy for antiretroviral treatment-naive patients with HIV infection or AIDS who were followed-up for at least 6 months were included in the meta-analysis. The proportion of patients with viral loads of <200-500 copies/ml at 6 and 12 months (total number of patients, 1619 and 761, respectively) was regressed to the mean or median baseline viral load and CD4(+) cell count. RESULTS: Thirty-six treatment arms from 30 studies were identified. Multivariate regression demonstrated a significant correlation between baseline CD4(+) cell count and virologic suppression at 6 and 12 months ( t = 2.85, p =.008; and t = 3.08, p =.010, respectively) but not between baseline viral load and virologic suppression ( t = 0.92, p =.365; and t = 1.31, p =.215, respectively). The same pattern was seen in a subanalysis of trials of nevirapine-containing therapy (CD4(+) cell count: t = 2.89, p =.014 at 6 months; viral load suppression: t = 0.84, p =.415). CONCLUSIONS: Baseline CD4(+) cell count was a better predictor of virologic suppression induced by triple combination therapy than was baseline viral load.     

Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy

BACKGROUND: Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary. METHODS: This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods. RESULTS: In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG. CONCLUSIONS: Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.     

Gender and clinical outcomes after starting highly active antiretroviral treatment: a cohort study

OBJECTIVE: To examine gender differences in clinical response to highly active antiretroviral treatment (HAART). METHODS: A cohort of HIV-positive individuals was examined. Outcomes assessed were hospital admission and disease progression (either a new AIDS diagnosis or death) after starting HAART. Hazard ratios (HRs) derived using Cox regression methods compared female-to-male rates, adjusting for other factors independently associated with outcome. RESULTS: Four hundred ninety-seven men and 146 women were followed up over a median of 13 months after starting HAART. Eighty-one percent of men were white, and 75% were homosexual. Fifty-eight percent of women were black African, and 86% were in the heterosexual risk category. The baseline CD4 count was higher in men than in women (191 vs. 145 x 10; p < .01), but viral loads were similar (5.2 vs. 5.1 log copies/ml, respectively; p = .13). Fifty-six percent of men and women were treatment na?ve. Eighteen percent of men and women were admitted during follow-up, with 17% of male admissions and 12% of female admissions being the result of an AIDS-defining illness. The HR for admission was 0.76 (95% confidence interval [CI]: 0.46-1.27; p = .30) for women relative to men. Eleven percent of the men and 8% of the women experienced progression. Eighty-eight percent of progressions were the result of a new AIDS diagnosis (46 in men, 11 in women), and 8 men died. The HR for progression was 0.70 (CI: 0.36-1.33; p = .28). CONCLUSIONS: Our results suggest a possible benefit in women compared with men in the rate of outcomes after HAART. Further analysis with longer follow-up or greater numbers would enable a more powerful analysis to be performed.     

Real versus virtual phenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Genotipo-Fenotipo di Resistenza (GenPheRex) trial

We compared viroimmunologic response after real phenotype (r-PHT) versus virtual phenotype (v-PHT) in patients failing highly active antiretroviral therapy (HAART). A total of 201 patients with >2 years of exposure, more than six experienced drugs, >1000 HIV RNA copies/mL, and on stable HAART for >6 months were randomized to the r-PHT or v-PHT arm. The primary end point was the proportion of HIV plasma viral load (pVL) <400 copies/mL. Secondary end points were absolute pVL change, proportion of pVL reduction >0.5 log(10) copies/mL, and absolute CD4 cell change. In the intention-to-treat-last observation carried forward analysis, study outcomes were not significantly different between arms over 48 weeks of follow-up: 20% and 24% pVL <400 copies/mL; 58% and 61% pVL reduction >0.5 log(10) copies/mL; -0.92 and -0.94(10) log copies/mL mean pVL decrease; and +41.6 and +94.4 cells/mm(3) mean absolute CD4 increase in the r-PHT and v-PHT arms, respectively. On-treatment analyses gave similar results. In the multivariate analysis of pVL <400 copies/mL, the following covariates were independent predictors at week 48: adherence (OR p= 0.25; p=.002), baseline CD4 (OR = 4.39; p=.007), intravenous drug use as risk factor for HIV acquisition (OR = 0.33; p=.024), and sensitivity score of the new regimens by biologic cut-offs (OR = 1.84; p=.029). Prescribed drugs for which patients were naive resulted in marginal prediction (OR = 1.93; p=.054). In conclusion, virologic and immunologic outcomes did not differ when r-PHT or v-PHT was used in this cohort of heavily pretreated patients. Several factors should be considered to take better advantage of resistance testing, including treatment history, clinical status, and patients' ability to adhere to treatment.     

Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups

OBJECTIVE: To determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy. METHODS: Individual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated. RESULTS: The sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively. CONCLUSIONS: For patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.     

Changes in outcome of persons initiating highly active antiretroviral therapy at a CD4 count less than 50 Cells/mm3

BACKGROUND: Although HIV treatment guidelines recommend highly active antiretroviral therapy (HAART) initiation before reaching a CD4 count of 200 cells/mm3, many people in resource-rich settings, and a substantial proportion in resource-limited settings, present at levels <50 cells/mm3. METHODS: Using UK Collaborative HIV Cohort data, we assessed virologic response to HAART for antiretroviral-naive persons initiating therapy at a CD4 count <50 cells/mm3. We also investigated changes in the probability of having a viral level <400 copies/mL at 48 weeks over calendar time adjusting for gender, age, exposure category, ethnicity, baseline CD4 count and viral load, and whether the regimen contained a protease inhibitor. RESULTS: At 12, 24, 36, and 48 weeks, 80%, 83%, 85%, and 83% of participants, respectively, had a viral level <400 copies/mL. This proportion rose from 1997 to 1998, falling slightly in the most recent calendar period. By far the most important predictor of virologic suppression was calendar year of starting HAART (odds ratio [OR] = 2.49, 4.28, and 3.28 for 1999 to 2000, 2001 to 2002, and 2003 to 2005, respectively, compared with 1997 to 1998). Women were more likely to have a viral level <400 copies/mL at week 48 compared with men (OR = 1.74, 95% confidence interval [CI]: 1.07 to 3.02), as were older individuals (OR = 1.46, 95% CI: 1.11 to 1.96 for every 10 years older). There was marginal or no evidence that other factors were associated with outcome. The estimated corresponding probabilities of achieving a viral level <50 copies/mL at week 48 were 71%, 75%, and 79% for a woman aged 25, 35, and 45 years, respectively, initiating HAART in the most recent calendar period. The respective probabilities for a man at those ages were 68%, 73%, and 78%. CONCLUSIONS: These data, albeit under conditions of good infrastructure for care delivery, are a useful comparator for other populations starting therapy at similar levels of immunodeficiency and may be valuable for evaluating the success of antiretroviral therapy rollout programs.     

Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial

BACKGROUND: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial. METHODS: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up for 24 weeks. The primary endpoint for definition of virologic success was a PVL <50 copies/mL during the 6 months following HAART discontinuation. RESULTS: Of the 29 patients enrolled, 26 completed the trial. Six months after HAART discontinuation, only 1 patient (3.8%, 95% CI: 0.1% to 19.6%) had PVL <50 copies/mL, whereas 6 of 26 (23.1%, 95% CI: 9.0% to 43.7%) had PVL <1000 copies/mL. Female gender was the only parameter significantly associated with a PVL <1000 copies/mL. No other parameter, either at baseline or before HAART discontinuation, predicted virologic success at week 108. A major protease inhibitor resistance mutation (L90M) developed in 3 patients. CONCLUSIONS: This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation.     

Response to efavirenz-containing regimens in previously antiretroviral-naive HIV-positive patients: the role of gender

BACKGROUND: We investigated the role of gender on response to efavirenz (EFV)-containing regimens in previously antiretroviral-naive patients. METHODS: All previously antiretroviral-naive individuals from the Royal Free Hospital in London starting EFV from 1996 onward were included. Treatment failure was defined as the first of 2 consecutive viral load measurements >500 copies/mL more than 24 weeks after starting EFV. Standard survival methods were used to assess time to discontinuation and to treatment failure. RESULTS: Ninety-six women and 337 men were included. Women were mostly of black African ethnicity (64.6%) with a heterosexual risk (94.8%), whereas men were mostly white (66.8%; P < 0.0001) with a homosexual risk (71.2%; P < 0.0001). Women had lower CD4 counts when starting EFV (median [interquartile range [IQR] = 126 [36, 220] cells/mm for women vs. 190 [109, 268] cells/mm for men; P = 0.0003). After 48 and 96 weeks, 38.8% (95% confidence interval [CI]: 28.8% to 48.7%) and 56.3% (95% CI: 45.8% to 66.9%) of women had discontinued EFV compared with 28.3% (95% CI: 23.4% to 33.2%) and 41.8% (95% CI: 36.3% to 47.3%) of men (P = 0.005). The percentage experiencing failure by 48 and 96 weeks when ignoring treatment changes but censoring at the date of discontinuing all treatment was 1.3% (0.0%, 3.9%) and 4.4% (0.0%, 9.3%) for women compared with 3.8% (1.6%, 6.0%; P = 0.49) and 5.8% (3.0%, 8.6%) for men. Median (IQR) CD4 count increases at 48 weeks were +166 (+89, +239) cells/mm for women and +176 (+93, +263) cells/mm for men. CONCLUSIONS: Women seem to have comparable virologic and immunologic outcomes to first-line EFV-containing regimens compared with men, although they are more likely to discontinue the drug.     

Are there gender differences in starting protease inhibitors, HAART, and disease progression despite equal access to care?

OBJECTIVES: To describe gender differences in starting and response to treatment regimens and long-term clinical outcome in a well-characterized regional population from the Southern Alberta HIV Clinic (SAC) of 1403 patients, where all medical care for HIV, including physician fees, laboratory tests, and antiretroviral drug costs is provided free of charge. DESIGN: Observational cohort study. METHODS: Cox proportional hazards models were used to examine the relative risk of starting treatment regimens and disease progression (new AIDS-defining illness or death). RESULTS: There are 126 women in the SAC (9.0%). The median CD4 lymphocyte count at first visit among all patients was 350 cells/mm3, and was significantly higher among women than men (428 cells/mm3 versus 345 cells/mm3, respectively; p = 0.0024). Participating women were less well educated than participating men; 29% of women did not proceed beyond a tenth grade education compared with 13% of men; only 28% of women went to college or received a degree in contrast to 40% of men (p <. 001). The proportion of women in the cohort has increased over the past 5 years (p <.001). During a median follow-up period of 35 months that dates back as far as 1985, 572 patients (40.8%) died or progressed to a new AIDS-defining illness, of whom 30 were women (5. 2%). In a multivariate Cox model stratified by calendar quartile of first visit and adjusted for latest CD4, AIDS status, age, exposure group, education, and prior treatment, women were significantly less likely to start highly active antiretroviral therapy (HAART; defined as at least three antiretrovirals taken consecutively; relative hazard [RH], 0.69; 95% confidence interval [CI], 0.49-0.98; p =.033), significantly less likely to start a protease inhibitor containing treatment regimen (RH, 0.71; 95% CI, 0.52-0.98; p =.040) and significantly less likely to start a HAART regimen including a protease inhibitor (RH, 0.69; 95% CI, 0.48-1.00; p =.049). After adjustment for potentially confounding variables such as CD4 lymphocyte count and treatment regimen, no difference in disease progression was found between men and women (RH, 0.77; 95% CI, 0. 49-1.19; p =.24). Among patients who started HAART, the CD4 lymphocyte count and viral load at starting treatment regimens was similar between men and women, as were the immunologic and virologic response following initiation of treatment. CONCLUSIONS: Despite free access to antiretrovirals, women in the SAC were significantly less likely to start HAART treatment regimens, and the reasons for this need further investigation. Response to treatment was similar between genders. No evidence was found for a poorer long-term clinical outcome in women, but given the proven large clinical benefits of HAART, this may change in the future.     

Subtle decreases in stavudine phenotypic susceptibility predict poor virologic response to stavudine monotherapy in zidovudine-experienced patients

To identify the level of phenotypic susceptibility for stavudine (d4T) that is associated with a diminished virologic response to d4T therapy, phenotyping was performed on archived baseline HIV isolates from 26 subjects who received d4T monotherapy in AIDS Clinical Trials Group (ACTG) 302 who had received >3 years of prior zidovudine (ZDV) monotherapy. Seven of 26 subjects achieved a virologic response of >0.3-log10 copies/mL reduction in plasma HIV RNA after 8 weeks of d4T. Responders had lower fold changes in susceptibility to d4T (1.0 vs. 1.6, p=.003), lower baseline viral loads (4.26 vs. 4.74 log10 copies/mL, p=.004), and fewer thymidine analog mutations (TAMS) (1 vs. 2, p=.059). Lower baseline d4T fold change in susceptibility predicted greater reductions in HIV RNA from baseline to week 8 after adjusting for baseline HIV RNA, ZDV fold change in susceptibility, and number of TAMS. Using the same phenotypic assay, drug susceptibility among 240 antiretroviral-naive patients found all HIV isolates to have d4T susceptibility 相似文献   

Modeling the time course of CD4 T-lymphocyte counts according to the level of virologic rebound in HIV-1-infected patients on highly active antiretroviral therapy

OBJECTIVE: To study the influence of the level of virologic rebound during combination antiretroviral therapy on the time course of the CD4 count. METHODS: Between January 1997 and December 1999, we enrolled 3736 patients from the French Hospital HIV Database who had an undetectable viral load on a first course of highly active antiretroviral therapy (HAART). Four levels of virologic rebound were defined on the basis of viral load values during the year following initial undetectability on HAART: group 1, all viral loads <500 copies/mL; group 2, all viral loads <5000 copies/mL; group 3, all viral loads <10,000 copies/mL; and group 4, at least 1 viral load >10,000 copies/mL. We developed a continuous time-homogeneous Markov process with 5 reversible stages defined by CD4 count intervals. RESULTS: CD4 counts increased continuously over time in each group. The smaller the virologic rebound, the stronger was the increase in the CD4 count (P < 0.0001). The mean CD4 cell count increments between months 2 and 6 were 26, 20, 11, and 2 cells/mm3 in groups 1, 2, 3, and 4, respectively. The rate of gain fell after month 6 and was almost nil in group 4. CONCLUSION: After achieving an undetectable viral load on HAART, immunologic reconstitution is possible whatever the subsequent level of viral replication, except among patients with high-level rebound, meaning that in patients with a long history of antiretroviral therapy and a reduced choice of antiretroviral drugs due to acquisition of resistances, delay in antiretroviral therapy switch can be possible in patients with low or intermediate rebound.     

Outcome of a second-line protease inhibitor-containing regimen in patients failing or intolerant of a first highly active antiretroviral therapy

The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) was investigated in 263 patients who were failed by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were virologic failure (decline in HIV RNA < 1 log10 copies/ml after > or = 2 months) and discontinuation due to intolerance/toxicity. During a median follow-up of 483 days (33-1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%) because of intolerance/toxicity; another 135 patients (51.3%) showed virologic failure. Independent factors associated with virologic failure (Cox's model) were 7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus < or = 6 months: 95% confidence interval [CI], 1.08-2.70) and gender (HR 1.58 males versus females: 95% CI, 1.04-2.30); the negatively associated factors were advanced age (HR 0.61 > 34 years versus < or = 34 years: 95% CI, 0.42-0.88), a saquinavir-containing first HAART (HR 0.57 versus indinavir: 95% CI, 0.34-0.93) and change due to intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35-0.98). The independent variables predictive of discontinuation due to intolerance/toxicity were the reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02-3.16) and the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir: 95% CI, 0.22-0.80). Given that patients who are failed by a first regimen are at high risk of having rescue therapy fail as well, second-line regimens including therapies directed by testing of drug resistance patterns of clinical viral isolates are warranted. Patients experiencing toxicity due to a first PI-containing regimen are at risk of toxicity to other PIs and should be addressed to PI-sparing HAART.