BackgroundAttrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression.Methods and findingsWe conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain.ConclusionsSame-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease.Trial registrationThis study is registered with ClinicalTrials.gov number NCT01900080

Thomas Campbell and colleagues report findings of a randomized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing.

Summary Background Mortality within the first 6 months after initiating antiretroviral therapy (ART) is common in resource-limited settings and is often due to tuberculosis (TB) among patients with advanced HIV disease. Isoniazid preventive therapy (IPT) is recommended in HIV-infected adults, but sub-clinical TB can be difficult to diagnose. We hypothesized that empiric TB treatment would reduce early mortality compared to IPT in high-burden settings. Methods We conducted a multi-country randomized clinical trial comparing empiric TB therapy (Empiric) vs. isoniazid preventive therapy (IPT) in HIV-infected outpatients initiating ART with CD4 counts <50 cells/mm3. Individuals were screened for TB using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available. The primary endpoint was survival (death or unknown status) at 24 weeks post randomization. Kaplan Meier estimates of the endpoint rates across arms were compared by the z-test. Registered at ClinicalTrials.gov (NCT01380080). Findings From October 31, 2011 until June 9, 2014, we randomized 850 participants (424 in Empiric arm and 426 in IPT arm); the median CD4 count at baseline was 18 cells/mm3 (IQR: 9, 32). At week 24, each arm had 22 primary endpoints, for rates of 5.2% in each arm (95% CI: 3.5% to 7.8% for Empiric and 3.4% to 7.8% for IPT; absolute risk difference of -0.06% (95% CI: −3.05% to 2.94%). Grade 3 or 4 signs or symptoms occurred in 50 (12%) in the Empiric arm and 46 (11%) in the IPT arm. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) in the Empiric arm and 97 (23%) in the IPT arm. Incident TB was more common in the Empiric arm (31 vs. 18 events, p=0.01). Interpretation Empiric TB therapy did not reduce mortality at 24 weeks in outpatient adults initiating ART with advanced HIV disease. The low mortality rate of the trial supports implementation of systematic TB screening and IPT in outpatients with advanced HIV disease.

Background Women progress to death at the same rate as men despite lower plasma HIV RNA (VL). We investigated sex-specific differences in immune activation and inflammation as a potential explanation. Methods Inflammatory and immune activation markers (IFN-γ, TNF-α, IL-6, IL-18, IP-10, CRP, LPS, sCD14) were measured at weeks 0, 24, and 48 post-cART in a random subcohort (n=215) who achieved virologic suppression in ACTG A5175 (PEARLS). Association between sex and changes in markers post-cART was examined using random effects models. Average marker differences and 95%CI were estimated using multivariable models. Results At baseline, women had lower median log10VL (4.93 vs 5.18 copies/mL, p=0.01), CRP (2.32 vs 4.62 mg/L, p=0.01), detectable LPS (39% vs 55%, p=0.04), and sCD14 (1.9 vs 2.3 mcg/mL, p=0.06) versus men. By week 48, women had higher IFN-γ (22.4 vs 14.9 pg/mL, p=0.05), TNF-α (11.5 vs 9.5 pg/mL, p=0.02), and CD4 (373 vs 323 cells/mm3, p=0.02). In multivariate analysis, women had greater increases in CD4 and TNF-α but less of a decrease in CRP and sCD14 compared to men. Conclusions With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality.

We analyzed mortality among 201 patients with AIDS and tuberculosis in Haiti. Patients who received a diagnosis of tuberculosis during the first 3 months after the initiation of antiretroviral therapy were 3.25 times more likely to die than were other patients with AIDS and tuberculosis. Failure to recognize active tuberculosis at initiation of antiretroviral therapy leads to increased mortality.