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Background: In South Africa, TB household contact tracing provides an opportunity for increased TB and HIV case finding. We aimed to determine the effect of two new potential interventions for TB contact tracing programmes: Point of Care CD4 (PoC CD4) on HIV linkage to care and household Isoniazid Preventive Therapy (IPT) provision on uptake and retention of IPT. Methods: A pragmatic, three-arm, cluster-randomized trial was undertaken. TB Household contacts were randomised to 3 arms: 1) Standard of Care TB and HIV testing (SOC); 2) SOC with POC CD4 for those testing HIV positive; 3) SOC with POC CD4 and IPT for eligible household members. Linkage to care within 90 days was assessed either through patient visits (at 10 weeks and 6 months) or via telephonic contact. Results: 2,243 index TB patients and 3,012 contacts (64,3% female, median age 30 years) were enrolled. On self-report, 26(1.2%) were currently receiving TB treatment and 1816 (60.3%) reported a prior HIV test. HIV testing uptake was 34.7% in the SoC arm, 40.2% in the PoC CD4 arm (RR1.16, CI 0.99–1.36, p-value = 0.060) and 39.9% in the PoC CD4 + HH-IPT arm (RR = 1.15, CI 0.99–1.35, p-value = 0.075). Linkage to care within 3 months was 30.8% in the SoC arm and 42.1% in the POC CD4 arms (RR 1.37; CI: 0.68–2.76, p-value = 0.382). 20/21 contacts (95.2%) initiated IPT in the PoC CD4 + HH-IPT arm, compared to 3/20 (15.0%) in the PoC CD4 arm (p = 0.004; p-value from Fisher’s exact test < 0.001). Among 3,008 contacts screened for tuberculosis, 15 (3.4%) had bacteriologically confirmed TB with an overall yield of TB of 0.5% (95% CI: 0.3%, 0.8%). Conclusions: Household PoC CD4 testing and IPT initiation is feasible. There was only weak evidence that PoCCD4 led to a small increase in HCT uptake and no evidence for an increase in linkage-to-care. IPT initiation and completion was increased by the household intervention. Although feasible, these interventions had low impact due to the low uptake of HIV testing in households. [ABSTRACT FROM AUTHOR]

Background: In high HIV prevalence settings, offering HIV testing may be a reasonable part of contact tracing of index tuberculosis (TB) patients. We evaluated the uptake of HIV counselling and testing (HCT) among household contacts of index TB patients and the proportion of newly diagnosed HIV-infected persons linked into care as part of a household TB contact tracing study. Methods: We recruited index TB patients at public health clinics in two South African provinces to obtain consent for household contact tracing. During scheduled household visits we offered TB symptom screening to all household members and HCT to individuals ≥14years of age. Factors associated with HCT uptake were investigated using a random effects logistic regression model. Results & Discussion: Out of 1,887 listed household members ≥14 years old, 984 (52%) were available during a household visit and offered HCT of which 108 (11%) self-reported being HIV infected and did not undergo HCT. Of the remaining 876, a total of 304 agreed to HCT (35%); 26 (8.6%) were newly diagnosed as HIV positive. In multivariable analysis, factors associated with uptake of HCT were prior testing (odds ratio 1.6; 95% confidence interval [CI]: 1.1–2.3) and another member in the household testing (odds ratio 2.4; 95% CI: 1.7–3.4). Within 3 months of testing HIV-positive, 35% reported initiating HIV care. Conclusion: HCT as a component of household TB contact tracing reached individuals without prior HIV testing, however uptake of HIV testing was poor. Strategies to improve HIV testing in household contacts should be evaluated. [ABSTRACT FROM AUTHOR]

Background: A prophylactic HIV-1 vaccine is a global health priority.Objective: To assess a novel vaccine platform as a prophylactic HIV-1 regimen.Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).Setting: United States, East Africa, and South Africa.Patients: Healthy adults without HIV infection.Intervention: 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.Measurements: Safety and immunogenicity and the effect of baseline vector immunity.Results: 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.Limitations: Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.Conclusion: Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.Primary Funding Source: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland. [ABSTRACT FROM AUTHOR]

During 6 months of treatment, we measured human im-munodeficiency virus (HIV)-1 virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1-infected patients with active tuberculosis (TB). The median virus load (baseline, 5.58 log[SUB10] copies/mL) significantly increased at 1 month (5.71 log[SUB10] copies/mL), then returned to near-baseline levels at 3 months (5.40 log[SUB10] copies/mL) and at 6 months (5.36 Log[SUB10] copies/mL). In contrast, the median CD4 counts increased at 1 month (186/mm[SUP3]), at 3 months (238/mm[SUP3]), and at 6 months (239/mm[SUP3]). CD4 counts and virus loads did not change during therapy. Expression of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of interleukin-6 decreased over time. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the association between early treatment outcomes and HIV status of patients with extensively drug-resistant (XDR) tuberculosis in South Africa. The case records of patients with XDR tuberculosis between August 2002 and February 2008 were analysed. The researchers used Cox proportional hazards regression models to assess the risk factors associated with the outcomes. It was found that patients with XDR tuberculosis, majority of them not infected with HIV, have poor management outcomes.