Objective-Evaluate the feasibility, fidelity, and effectiveness of an HIV prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal, South Africa.Methods-Total of 152 HIV-infected patients, aged 18 years and older, receiving clinical care at an urban hospital in South Africa, were randomly assigned to intervention or standard-of-care control counselors. Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior. Self-report questionnaires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months.Results-Intervention was delivered in 99% of routine patient visits, and included a modal 8 of 8 intervention steps. Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline, patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events. There

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.

We assessed the incidence and predictors of unprotected sex among 152 HIV-positive patients in clinical care in KwaZulu-Natal, South Africa. Nearly 50% were sexually active; 30% of those reported unprotected sex. Alcohol use during sex, reporting forced sex, sex with a perceived HIV-positive partner, and sex with a casual partner predicted more unprotected sex, whereas HIV status disclosure was related to less unprotected sex. These findings highlight the need for linking HIV prevention and care in Africa.

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.

Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation.

Context Sustainable interventions are needed to minimize HIV risk behavior among people living with HIV (PLWH) in South Africa on antiretroviral therapy (ART), a significant proportion of whom do not achieve viral suppression. Objective To determine whether a brief lay counselor delivered intervention implemented during routine care can reduce risky sex among PLWH on ART. Design Cluster randomized 16 HIV clinical care sites in KwaZulu Natal, South Africa, to intervention or standard-of-care. Setting Publicly funded HIV clinical care sites. Patients 1891 PLWH on ART received the HIV prevention counseling intervention (n = 967) or standard-of-care counseling (n = 924). Intervention Lay counselors delivered a brief intervention using motivational interviewing strategies based on the Information—Motivation—Behavioral Skills (IMB) model during routine clinical care. Main Outcome Measures Number of sexual events without a condom in the past four weeks with partners of any HIV status, and with partners perceived to be HIV-negative or HIV-status unknown, assessed at baseline, 6, 12, and 18 months. Results Intervention participants reported significantly greater reductions in HIV risk behavior on both primary outcomes, compared to standard-of-care participants. Differences in STI incidence between arms were not observed. Conclusion Effective behavioral interventions, delivered by lay counselors within the clinical care setting, are consistent with the strategy of linking HIV care and HIV prevention and integrating biomedical and behavioral approaches to stemming the HIV epidemic.

Introduction Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral (ART) initiation in HIV-infected individuals is not well characterized. Methods We conducted a case-cohort study (n=332) within a randomized trial comparing three ART regimens in 1571 HIV treatment-naïve adults from nine countries. A subcohort of 30 patients was randomly selected from each country (n=270). Cases (n=77; main cohort=62, random subcohort=15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pre-treatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pre-treatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models. Results Median pre-treatment CD4+ T-cell count was 170 cells/mm3; 47.3% were female; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, prior TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pre-treatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI 1.54–18.43) and vitamin D (aHR 3.66, 95%CI 1.16–11.51) were associated with TB post-ART. Conclusion In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV infected patients starting ART in resource-limited, highly-TB-endemic settings.

Background and Aims HIV-infected adults have increased risk of several individual micronutrient deficiencies. However, the prevalence and risk factors of concurrent and multiple micronutrient deficiencies and whether micronutrient concentrations change after antiretroviral therapy (ART) initiation have not been well described. The objective of this study was to determine the prevalence and risk factors of individual, concurrent and multiple micronutrient deficiencies among ART-naïve HIV-infected adults from nine countries and assess change in micronutrient status 48 weeks post-ART initiation. Methods A random sub-cohort (n=270) stratified by country was selected from the multinational PEARLS clinical trial (n=1571 ART-naïve, HIV-infected adults). We measured serum concentrations of vitamins A, D (25-hydroxyvitamin), E, carotenoids and selenium pre-ART and 48 weeks post-ART initiation, and measured vitamins B6, B12, ferritin and soluble transferrin receptor at baseline only. Prevalence of single micronutrient deficiencies, concurrent (2 coexisting) or conditional (a deficiency in one micronutrient given a deficiency in another) and multiple (≥3) were determined using defined serum concentration cutoffs. We assessed mean changes in micronutrient concentrations from pre-ART to week 48 post-ART initiation using multivariable random effects models. Results Of 270 participants, 13.9%, 29.2%, 24.5% and 32.4% had 0, 1, 2 and multiple deficiencies, respectively. Pre-ART prevalence was the highest for single deficiencies of selenium (53.2%), vitamin D (42.4%), and B6 (37.3%) with 12.1% having concurrent deficiencies of all three micronutrients. Deficiency prevalence varied widely by country. 48 weeks post-ART initiation, mean vitamin A concentration increased (p<0.001) corresponding to a 9% decrease in deficiency. Mean concentrations also increased for other micronutrients assessed 48 weeks post-ART (p<0.001) but with minimal change in deficiency status. Conclusions Single and multiple micronutrient deficiencies are common among HIV-infected adults pre-ART initiation but vary between countries. Importantly, despite increases in micronutrient concentrations, prevalence of individual deficiencies remains largely unchanged after 48 weeks on ART. Our results suggest that ART alone is not sufficient to improve micronutrient deficiency.