Micronutrient supplementation increases genital tract shedding of HIV-1 in women: results of a randomized trial

To test the hypothesis that micronutrient supplementation decreases genital HIV-1 shedding, a double-blind, randomized, placebo-controlled trial of 6 weeks of multivitamin plus selenium supplementation vs. placebo was conducted among 400 HIV-1-seropositive, nonpregnant, antiretroviral-naive women in Mombasa, Kenya. Primary outcome measures included cervical and vaginal shedding of HIV-1-infected cells and RNA. Secondary outcomes included plasma viral load and CD4 count. Surprisingly, the odds of detection of vaginal HIV-1-infected cells were 2.5-fold higher (P = 0.001) and the quantity of HIV-1 RNA in vaginal secretions was 0.37 log10 copies/swab higher (P = 0.004) among women who received micronutrients in comparison to placebo, even after adjustment for potential confounders including baseline HIV-1 shedding and CD4 count. The increase in vaginal HIV-1 shedding was greatest among women who had normal baseline selenium levels. Micronutrient supplementation resulted in higher CD4 (+23 cells/microL, P = 0.03) and CD8 (+74 cells/microL, P = 0.005) counts compared with placebo but did not alter the plasma viral load. In this randomized trial, micronutrients resulted in higher levels of genital HIV-1 shedding compared with placebo. The potential benefit of micronutrient supplementation in HIV-1-seropositive women should be considered in relation to the potential for increased infectivity.     

Disadvantages of structured treatment interruption persist in patients with multidrug-resistant HIV-1: final results of the CPCRA 064 study

BACKGROUND: We report the final results of Community Programs for Clinical Research on AIDS (CPCRA-064) study, a multicenter, prospective, randomized, controlled trial that determines the long-term clinical impact of structured treatment interruption (STI) in patients with multidrug-resistant (MDR) HIV-1. METHODS AND RESULTS: Two hundred seventy-four patients on stable antiretroviral therapy with MDR HIV-1 treatment failure were randomized to a 4-month STI, followed by an optimized antiretroviral regimen (STI arm, n = 140) or an immediate change to an optimized antiretroviral regimen (control arm, n = 134). Main outcome measures were progression of disease or death and changes from baseline in HIV RNA levels (log copies/mL) and CD4 cell counts (cells/mm). The median baseline HIV RNA level was 5.0 log copies/mL, the median CD4 count was 147 cells/mm, and the nadir CD4 count was 32 cells/mm. The median follow-up was 37 months. After the STI period, there were no differences in HIV RNA level responses between treatment arms. Differences in CD4 count responses always favored the control arm, with an advantage of 84 cells from 0 to 4 months (P < 0.0001), 50 cells from 4 to 12 months (P < 0.0001), 45 cells from 12 to 24 months (P = 0.006), and 43 cells after 24 months (P = 0.07). Rates in the STI and control arms for first progression-of-disease event or death were 17.5 and 14.3, respectively (hazard ratio = 1.28; P = 0.22). CONCLUSION: STI before changing regimens in patients with MDR HIV-1 treatment failure has a prolonged negative impact on CD4 cell count recovery and does not confer progression of disease or virologic benefits.     

Didanosine dosed once daily is equivalent to twice daily dosing for patients on double or triple combination antiretroviral therapy. The AI454-147 Team

OBJECTIVE: To compare the antiviral activity, effect on CD4 cell count, and tolerability of didanosine (ddI) administered once daily and twice daily in HIV-1-infected patients receiving ddI with stavudine or zidovudine, with or without a protease inhibitor. The study was designed to demonstrate that once-daily dosing of ddI was not inferior to twice-daily dosing. DESIGN: Randomized, open-label, multicenter, two-arm study. PATIENTS AND METHODS: 121 HIV-1-infected adults on a stable regimen including ddI (twice daily) during the previous 3 months with a stable viral load <10,000 copies/ml started therapy. Of these, 62 were randomized to switch to a combination that included ddI once daily and 59 to continue with ddI twice daily. The ddI dose was 400 mg/day (250 mg/day if body weight was <60 kg). The primary efficacy analysis compared the time-averaged difference (TAD) between the two treatment regimens in change from baseline log10 plasma HIV-1 RNA levels over 24 weeks of therapy, with an equivalence margin between the two treatment groups of <0.5 log10 copies/ml. RESULTS: At week 24, the mean plasma HIV-1 RNA level had increased by 0.31 and 0.17 log10 copies/ml in the ddI once-daily and ddI twice-daily groups, respectively. The time-averaged difference between the two groups in change from baseline plasma HIV-1 RNA levels over 24 weeks was (0.05 log10 copies/ml (95% confidence interval, -0.21 to +0.12 log10 copies/ml), indicating that the antiviral activity of ddI once daily is similar to that of ddI twice daily. After 24 weeks of treatment, changes from baseline in CD4 cell counts were similar in the two groups. Both regimens were generally well-tolerated. CONCLUSIONS: Once-daily and twice-daily ddI are equally effective at reducing plasma HIV-1 RNA levels when used in a combination regimen with stavudine or zidovudine, with or without a protease inhibitor.     

Long-term safety and antiretroviral activity of hydroxyurea and didanosine in HIV-infected patients

Long-term safety, immunologic effects, and antiretroviral activity of hydroxyurea and didanosine were evaluated in this retrospective study. Some 65 HIV-1-infected patients (39 of whom were antiretroviral naive) were studied (mean baseline CD4 count, 362 cells/mm3; mean plasma HIV-1 RNA viral load, 4.8 log10 copies/ml). The mean treatment duration was 20 months. Overall tolerance was good: 15 patients interrupted treatment because of clinical or biologic side effects. Four patients experienced a category B event. Patients had a mean increase of 27 CD4 cell counts after 12 months, of 112 after 24 months and of 59 after 36 months. They had a mean 1. 03 log10 fall in HIV-1 RNA after 12 months, 1.59 log10 after 24 months, and 1.27 log10 after 36 months. After 12 months, 35% developed an HIV-1 RNA viral load <200 copies/ml, 53% after 24 months, and 36% after 36 months. Those whose viral load became undetectable after 12 months have significantly lower baseline RNA values (p =.03). Fourteen patients had a viral load <3.4 log10 copies/ml after 24 months of the double therapy. A prolonged viral load suppression can be achieved using a simple combination of two drugs that are inexpensive and well tolerated.     

Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand

BACKGROUND: Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. METHODS: HIV-1- and herpes simplex virus type 2-coinfected women aged 18-49 years with CD4 counts >200 cells/microL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. RESULTS: Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/microL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). CONCLUSIONS: Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission.     

HIV-1 DNA in peripheral blood mononuclear cells is strongly associated with HIV-1 disease progression in recently infected West African adults

OBJECTIVE: To analyze the association between the HIV-1 DNA level in peripheral blood mononuclear cells (PBMCs) and disease progression in recently infected West African adults. METHODS: HIV-1 DNA levels were measured in the PBMCs of 200 adults in the French National Agency for Research on AIDS and viral Hepatitis (ANRS) 1220 cohort who had recently been infected with HIV-1. The association between baseline HIV-1 DNA levels and disease progression was analyzed using multivariate Cox regression. Disease progression was defined as the occurrence of any of the following outcomes: death, first World Health Organization stage 3-4 event, or CD4 count<200/mm. RESULTS: About 200 participants were followed for a median of 30 months. At baseline, the median time from HIV-1 seroconversion was 9 months, median CD4 T-cell count was 471/mm, median HIV-1 DNA level was 3.0 log10 copies/10 PBMCs, and median plasma HIV-1 RNA level was 4.6 log10 copies/mL. The 5-year probability of remaining free of any outcome was 0.74 [95% confidence interval (CI): 0.61 to 0.83] and 0.36 (95% CI: 0.23 to 0.49) in patients with baseline HIV-1 DNA3.0 log10 copies/10 PBMCs, respectively (P<0.001). The adjusted hazard ratio of disease progression was 2.17 in patients with HIV-1 DNA>3.0 log10 copies/10 PBMCs compared with other patients (95% CI: 1.24 to 3.80, P=0.007). The only other factor associated with progression was follow-up CD4 count (hazard ratio=1.23 per 100 cells/mm decrease; 95% CI: 1.07 to 1.41, P=0.003). DISCUSSION: PBMC HIV-1 DNA level was strongly associated with HIV-1 disease progression, even after adjusting for HIV-1 RNA and CD4 T-cell count. Further studies should assess whether patients with high HIV-1 DNA levels should start antiretroviral therapy earlier than other patients.     

High-dose saquinavir plus ritonavir: long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response

The year-long antiviral efficacy of a high-dose salvage regimen consisting of saquinavir (800 mg twice daily) plus ritonavir (400 mg twice daily) was evaluated in 58 HIV-positive patients who had seen no improvement under first-line protease inhibitor-containing regimens, nor in baseline predictors of virologic response. The efficacy of therapy was determined by CD4+/CD8+ and HIV-1 RNA values. The primary endpoint of our study was the percentage of patients with HIV-1 RNA levels <200 copies/ml (virologic success) at 6 and 12 months of of follow-up. Secondary endpoints were log10 reduction in HIV-1 RNA levels and CD4+ increases through follow-up. Surrogate markers related with a lower HIV-1 RNA area under the curve were identified at baseline. Kaplan-Meier analysis and Cox proportional hazards models were applied to identify baseline predictors of achieving viral suppression at <200 copies/ml. All analyses were intention to treat-last observation carried forward. Patients achieved a median HIV-1 RNA level reduction of >0.5 log through 1 year (-0.59 log10 at 12 months), as well as CD4+ counts increased significantly (89 cells/mm3 at 12 months). Overall, 53% of patients were likely to achieve HIV-1 RNA levels <200 copies/ml at 6 months. Seventy-six percent of patients who started therapy at HIV-1 RNA levels <5000 copies/ml but only 42% with baseline viral load of 5000 to 30,000 copies/ml and 18.7% with baseline viral load >30,000 copies/ml were likely to achieve viral suppression at 6 months (p < .001, log-rank test). Patients with baseline HIV-1 RNA levels between 5000 and 30,000 copies/ml (relative hazard [RH], 0.39; 95% confidence interval [CI], 0.01 to 0.98; p = .0396) and patients with baseline HIV-1 RNA levels >30,000 copies/ml (RH, 0.20; 95% CI, 0.07-0.61; p = .0040) were less likely to reach undetectable HIV-1 RNA levels than those with baseline HIV-1 RNA levels <5000 copies/ml. Salvage highly active antiretroviral therapy (HAART) strategies including saquinavir (SQV) at high doses plus ritonavir (RTV) exert a significant long-term efficacy in more than half of PI-experienced patients without significant additional toxicity. This therapeutic efficacy is strongly implemented by a switch at the lower HIV-1 RNA levels.     

Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients

A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research (35% female, 71% African American, 21% Hispanic, and 20% injection drug users [IDUs]) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple, compact, twice-daily triple nucleoside regimen containing a lamivudine (150 mg)/zidovudine (300 mg) combination (COM) tablet plus abacavir (ABC), 300 mg. At baseline, the patients' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4+ cell count was 379 cells/mm3. Patients were randomized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling (EI + RC; n = 96) or to routine counseling alone (RC; n = 99). No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels <40 copies/mL (60% [33/55] vs. 55% [38/69]; P = 0.529) or <400 copies/mL (80% [44/55] vs. 80% [55/69]; P = 0.689) at week 24 (intent-to-treat observed analysis), increase in median CD4 cell count above baseline at week 24 (78.3 vs. 104.8 cells/mm3; P = 0.498), or mean overall adherence rates as measured by the Medication Event Monitoring System (MEMS) (70% vs. 74%). COM + ABC was generally well tolerated, and no association was observed between interruptions in treatment and the development of ABC hypersensitivity (5 suspected cases). In conclusion, in underrepresented patients, the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC.     

A comparison of genital HIV-1 shedding and sexual risk behavior among Kenyan women based on eligibility for initiation of HAART according to WHO guidelines

BACKGROUND: Guidelines for initiating antiretrovirals are based on markers of advanced disease and are not directly linked to markers of HIV-1 transmission such as viral shedding. METHODS: We evaluated genital HIV-1 shedding and risk behavior among 650 antiretroviral-na?ve women stratified by WHO criteria for initiating antiretrovirals based on CD4 count and symptoms. RESULTS: Genital HIV-1 concentrations increased in stepwise fashion with declining CD4 counts and the presence of symptoms. Compared with the reference group (asymptomatic with CD4 >350 cells/microL), those with advanced immunosuppression (CD4 <200 cells/microL) had significantly higher cervical HIV-1 RNA concentrations (2.4 log10 copies/swab vs. 3.8 log10 copies/swab, P < 0.001). However, women with CD4 counts <200 cells/microL were also less likely than the reference group to report intercourse during the past week (58% vs. 26%, P < 0.001). CONCLUSIONS: Antiretroviral guidelines focusing on individuals with the most advanced immunosuppression will target those with the highest genital HIV-1 concentrations. However, individuals with less advanced immunosuppression also have high levels of genital HIV-1 and may be more sexually active. The effect of increased antiretroviral availability on the spread of HIV-1 might be enhanced by extending treatment, in addition to other risk reduction services, to those with less advanced disease.     

Response to highly active antiretroviral therapy at 6 months and long-term disease progression in HIV-1 infection

OBJECTIVE: To compare the long-term prognostic significance of different definitions of immunologic and virologic responses to highly active antiretroviral therapy (HAART) at 6 months. METHODS: This was a prospective study conducted in 68 French hospitals. HAART was initiated in 2236 protease inhibitor-naive patients included in the French Hospital Database on HIV. Multivariate Cox proportional hazard models measuring time from 6 months after starting HAART were used to compare the strength of the association between different definitions of immunologic and virologic responses at 6 months and subsequent progression to AIDS or death. The Akaike's Information Criteria were used to identify the most appropriate model. RESULTS: During a median follow-up of 58 months, 325 patients experienced an AIDS-defining event or died. The model that fitted best was the model in which the CD4 cell count and plasma HIV-1 RNA values attained at 6 months were considered. The risk of clinical progression at 5 years ranged from 7% (95% confidence interval [CI]: 4-10) in patients whose CD4 cell count at 6 months was >or=350 cells/microL and whose HIV-1 RNA concentration was <3 log10 copies/mL to 63% (95% CI: 52-75) in patients whose CD4 cell count at 6 months was <100 cells/microL and whose HIV-1 RNA concentration was >or=5 log10. CONCLUSIONS: Plasma HIV-1 RNA concentration and CD4 cell count should be taken into account independently when evaluating early response to treatment. The persistent impact of early response on clinical progression at 5 years emphasizes the major importance of the success of first-line HAART.     

Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine.

BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine (d4T/3TC/NVP) is extensively used as initial antiretroviral regimen in developing countries. K65R mutations that occur after failing this regimen prevent the use of tenofovir, didanosine, and abcavir in the second-line regimen. OBJECTIVES: To determine the prevalence and risk factors of K65R mutations after failing d4T/3TC/NVP. STUDY DESIGN: Genotypic resistance testing was conducted among HIV-1 infected patients who experienced virological failure with an initial regimen of d4T/3TC/NVP. RESULTS: There were 122 patients who received antiretroviral therapy (ART) for a median (IQR) duration of 19 (13-27) months. Median (IQR) CD4 cell count and plasma HIV-1 RNA at virological failure was 174 (109-264) cells/mm(3) and 4.0 (3.7-4.6)log copies/mL, respectively. The prevalence of K65R mutations was 7%. Patients with K65R mutations had higher plasma HIV-1 RNA at virological failure compared to patients without K65R mutations (4.9log copies/mL vs. 4.0log copies/mL, p=0.001). By logistic regression analysis only plasma HIV-1 RNA at failure correlated with the occurrence of K65R mutations [OR 4.2 (95% CI, 1.5-11.2) per 0.5log copies/mL increment of HIV-1 RNA]. CONCLUSIONS: Seven percent of patients had K65R mutations after failing an initial d4T/3TC/NVP regimen. Tenofovir, didanosine, and abcavir cannot be used in second-line regimen for these patients. HIV-1 RNA at the time that virological failure was detected correlated with the occurrence of K65R mutations.     

Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3

OBJECTIVE: In POWER 1 and POWER 2, darunavir (TMC114) with low-dose ritonavir (darunavir/r) demonstrated greater efficacy versus control protease inhibitors (PIs). To examine the efficacy and safety of the selected darunavir/r dose further, additional patients were analyzed. METHODS: Treatment-experienced HIV-1-infected patients received darunavir/r at a dose of 600/100 mg twice daily plus an optimized background regimen. The primary intent-to-treat analysis was the proportion of patients with an HIV-1 RNA reduction >or=1 log10 at week 24. RESULTS: Three hundred twenty-seven patients were treated; the baseline mean HIV-1 RNA was 4.6 log10 copies/mL, and the median CD4 count was 115 cells/mm3 (median primary PI mutations = 3, PI resistance-associated mutations = 9). Two hundred forty-six patients reached week 24 by the cutoff date and were included in the efficacy analysis: 65% and 40% achieved HIV-1 RNA reductions of >or=1 log10 and <50 copies/mL, respectively, at week 24. The mean CD4 count increase was 80 cells/mm3. The most common adverse events (AEs) were diarrhea (14%), nasopharyngitis (11%), and nausea (10%). Nine (3%) patients discontinued treatment because of AEs or HIV-1-related events. Six treatment-unrelated deaths (2%) were reported. CONCLUSIONS: These results corroborate POWER 1 and POWER 2. In this larger set of treatment-experienced patients, darunavir/r at a dose of 600/100 mg twice daily provided substantial virologic and immunologic responses and was generally safe and well tolerated.     

Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors

From a study of 71 HIV-1-infected patients receiving abacavir in combination with 1 of 5 different HIV-1 protease inhibitors (indinavir, ritonavir, saquinavir, nelfinavir, or amprenavir), we found that the baseline HIV-1 RNA levels were highly predictive of the viral decay rates. The baseline HIV-1 RNA levels were negatively correlated with the first phase viral decay rates (r = -0.77, P < 0.001) and positively correlated with the second phase viral decay rates (r = 0.68, P < 0.001). In addition, the first phase viral decay rate was positively correlated with CD4+ cell increases. No significant correlation was found between viral decay rates and longer term (24 weeks) virologic responses, and no difference in viral decay rates was found among the 5 study regimens. These data suggest that the potency of the 5 treatment regimens was similar and was not predictive of long-term virologic failure.     

Relevance of HIV-1-specific CD4+ helper T-cell responses during structured treatment interruptions in patients with CD4+ T-cell nadir above 400/mm3

OBJECTIVES: To analyze the dynamics of both HIV-1-specific CD4 and CD8 T-cell responses during structured treatment interruptions (STIs) in chronically HIV-1-infected (CHI) patients and to correlate them with the viral set point achieved. METHODS: Forty-five early-stage CHI patients who were on highly active antiretroviral therapy (HAART) for at least 1 year and underwent STI were included. Plasma viral load (VL), peripheral blood mononuclear cell (PBMC) lymphoproliferative (LPR) response to HIV p24 protein, and HIV-1 epitope-specific interferon-gammarelease from CD8 T cells were measured over a minimum study period of 2 years. RESULTS: VL set point during final STI was both significantly lower than, and positively correlated to, baseline VL (P < 0.0001: mean VL reduction 0.77 log10, and r = 0.42, P = 0.004, respectively). CD4 LPRs to p24 increased significantly (P = 0.001) between day 0 of the first STI cycle and 4th STI but decreased thereafter. VL set point during final STI was significantly and negatively correlated with LPRs to p24 at both 2nd STI and 4th STI. Nevertheless, at week 52, 12 weeks after the end of the last STI, LPRs were weak and transient in all patients and were not correlated with VL set point. Moreover, the magnitude and breadth of HIV-1-specific CD8 T-cell responses increased significantly (P < 0.0001) between day 0 and week 52. The largest increases occurred during the final STI. Even though VL reached set point by week 12 of the final STI, HIV-1-specific CD8 T-cell responses did not stabilize but rather increased until the end of the follow-up and did not correlate with plasma VL (r = 0.01, P = 0.88). CONCLUSIONS: STIs do not lead to control of viral replication in CHI patients, probably due to the fact that boosted CTL responses lack strong and durable helper T-cell responses. To reset the VL set point, new approaches that effectively augment and preserve helper T-cell responses should be investigated.     

Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months

OBJECTIVE: To determine the patterns and predictors of genital tract HIV-1 RNA levels during a 36-month period. METHODS: HIV-1 RNA levels were measured blood in plasma and the genital tract (by cervicovaginal lavage [CVL]) at baseline before highly, active antiretroviral therapy, at 2 and 4 weeks and every 6 months. Viral loads were measured using nucleic acid sequence-based amplification assay with a lower limit of detection of 2.6 log10 copies/mL. RESULTS: Ninety-seven women had a median of 30.4 months' follow-up, with 530 paired PVL and CVL specimens. The strongest predictor of CVL fluid HIV-1 RNA detection was PVL of more than 2.6 log10 copies/mL, with an odds ratio of 13.7 (P < 0.0001). Each log10 unit increase in PVL increased the odds of detecting HIV-1 RNA in CVL fluid by 2.6 folds (P = 0.0002). Cervicovaginal lavage fluid HIV-1 RNA exceeded PVL on 5% of visits. When patients achieved undetectable levels of HIV-1 RNA in both plasma and CVL fluid, rebound of HIV-1 RNA occurred in plasma first or concurrently with CVL fluid HIV-1 RNA. CONCLUSIONS: Plasma viral load is the strongest predictor of CVL fluid HIV-1 RNA detection. Cervicovaginal lavage fluid HIV-1 RNA levels are generally lower than PVL. Plasma viral load is more likely to rebound first or at the same time as CVL fluid viral load.     

It is safe to stop antiretroviral therapy in patients with preantiretroviral CD4 cell counts >250 cells/microL

OBJECTIVE: To study clinical, immunologic, and virologic outcomes in patients who stop antiretroviral therapy (ART) with relatively preserved CD4 cell counts. DESIGN AND METHODS: Patients with a documented CD4 cell count >250 cells/microL who stopped ART for any reason for at least 5 weeks were studied. Relevant clinical and laboratory data were collected using a standardized data collection form. MAIN OUTCOME MEASURES: Patients were monitored for outcomes including Centers for Disease Control (CDC) category B or C events, time to restarting ART, and time to reaching a CD4 cell count of < or = 250 cells/microL. RESULTS: A total of 107 patients were included. The median time on ART was 45 months and median number of antiretroviral medications was 4. The median pre-ART CD4 cell count and HIV viral load were 463 cells/microL and 4.35 log copies/mL, respectively. The median CD4 cell at time of ART stop was 739 cell/microL. The slope of the CD4 decrease was 65 cells/mo in the first 2 months, which was greater than the subsequent decline of 8 cells/mo thereafter (P < 0.01). Similarly the median viral load increase was 2.54 log copies/mL in the first 2 months after stopping and was unchanged after that point. Two patients experienced the retroviral rebound syndrome after ART cessation but no CDC category B or C events were observed during 10 months of follow-up. The median time from stopping ART to reaching the combined endpoint of CD4 <250 or restarting ART was 8.9 months. In multivariate analysis, pre-ART CD4 cell count >250 was protective of reaching the combined endpoint (odds ratio = 0.156, P = 0.03). Other predictors of reaching the combined endpoint in multivariate analysis were older age and number of prior ART agents. Patients who restarted ART had a favorable virologic and immunologic response. CONCLUSIONS: Patients with relatively high CD4 cell counts prior to starting ART did well after stopping ART. Pre-ART CD4 cell count can be used to predict outcomes after ART cessation.     

Efficacy and safety of an anti-retroviral combination regimen including either efavirenz or lopinavir–ritonavir with a backbone of two nucleoside reverse transcriptase inhibitors

The efficacy and safety of a combination regimen including either efavirenz or lopinavir-ritonavir was examined in a cohort of 65 patients positive for human immunodeficiency virus-1 (HIV-1). Both the efavirenz (n = 33, 18 anti-retroviral naive) and lopinavir-ritonavir (n = 32, 15 naive) regimens achieved significant changes from baseline CD4 cell counts and HIV RNA levels after 108 weeks (p < 0.01). Despite diminished immunological and virological parameters at study entry, the lopinavir-ritonavir group showed greater virological effects than the efavirenz group after 108 weeks (median change 3.3 log(10), interquartile range (IQR) 2.2-3.8 log(10) vs. 2.4 log(10), IQR 0.9-3.3 log(10), respectively, p 0.004). Use of lopinavir-ritonavir, in contrast to use of efavirenz, was associated with significant hypertriglyceridaemia.