METHODS: In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells per microliter who had CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1 CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells per microliter within a 6-month period (confirmed CD4 <200). A comparison of time with single and confirmed CD4 <200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprising the same patients with annual CD4 testing by removing every second CD4 count.
RESULTS: Among 1538 patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells per microliter were significantly more likely to experience confirmed CD4 <200 compared with patients with higher baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P < 0.001 versus baseline CD4 ≥500 cells/μL]. Cumulative probabilities of confirmed CD4 <200 was also higher in patients with baseline CD4 200-249 cells per microliter compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4 <200 between biannual and annual CD4 measurement (P = 0.336).
CONCLUSIONS: Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells per microliter may be sufficient for clinical management.
METHODS: Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.
FINDINGS: Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).
INTERPRETATION: Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.
FUNDING: The Kirby Institute and the Australian National Health and Medical Research Council.
DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.
METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.
RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.
CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.
METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.
RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.
CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.