Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E, which induces neuroAIDS in a high proportion of rhesus macaques and identified enhanced antagonism of the host innate factor BST-2 as an important factor in the macrophage tropism and initial neuro-invasion of this isolate. In the present study, we further developed this model by deriving a molecular clone SIVsm804E-CL757 (CL757). This clone induced neurological disorders in high frequencies but without rapid disease progression and thus is more reflective of the tempo of neuroAIDS in HIV-infection. NeuroAIDS was also induced in macaques co-inoculated with CL757 and the parental AIDS-inducing, but non-neurovirulent SIVsmE543-3 (E543-3). Molecular analysis of macaques infected with CL757 revealed compartmentalization of virus populations between the CNS and the periphery. CL757 exclusively targeted the CNS whereas E543-3 was restricted to the periphery consistent with a role for viral determinants in the mechanisms of neuroinvasion. CL757 would be a useful model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.

SETTING: Contact tracing using pediatric index cases has not been adequately investigated in high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence settings. OBJECTIVE: To determine the yield of contact tracing in household contacts of pediatric TB index cases in Botswana. DESIGN: Index cases included all pediatric (age ⩽13 years) TB admissions from January 2009 to December 2011 to Botswana’s largest referral hospital. A contact tracing team identified cases, conducted home visits, symptom-screened contacts and referred those with ⩾1 TB symptoms. The primary outcome was newly diagnosed TB in a contact. RESULTS: From 163 pediatric index cases, 548 contacts were screened (median 3 contacts/case, interquartile range [IQR] 2–4). Of these, 49 (9%) were referred for positive symptoms on screening and 27/49 (55%) were evaluated for active TB. Twelve new TB cases were diagnosed (12/548, 2.2%); the median age was 31 years (IQR 23–38); 11 (92%) were smear-positive. Ten (83%) had known HIV status: 7 (70%) were HIV-positive. To find one new TB case, the number needed to contact trace (index cases/new cases) was 13.6, and the number needed to screen (contacts/new cases) was 46. CONCLUSION: This yield of contact tracing using pediatric index cases is similar to the traditional adult index case approach. Improving the proportion of symptomatic contacts evaluated may increase yield.

Objective: To assess the impact of alcohol use on HIV care cascade outcomes. Design: Cross-sectional analyses. Methods: We evaluated HIV care cascade outcomes and alcohol use in adults (≥15 years) during baseline (2013--2014) population-based HIV testing in 28 Kenyan and Ugandan communities. ‘Alcohol use’ included any current use and was stratified by Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores: nonhazardous/low (1--3 men/1--2 women), hazardous/medium (4--5 men/3--5 women), hazardous/high (6--7), hazardous/very-high (8--12). We estimated cascade outcomes and relative risks associated with each drinking level using targeted maximum likelihood estimation, adjusting for confounding and missing measures. Results: Among 118 923 adults, 10 268 (9%) tested HIV-positive. Of those, 10 067 (98%) completed alcohol screening: 1626 (16%) reported drinking, representing 7% of women (467/6499) and 33% of men (1 159/3568). Drinking levels were: low (48%), medium (34%), high (11%), very high (7%). Drinkers were less likely to be previously HIV diagnosed (58% [95% CI: 55--61%]) than nondrinkers [66% (95% CI: 65–67%); RR: 0.87 (95% CI: 0.83–0.92)]. If previously diagnosed, drinkers were less likely to be on ART [77% (95% CI: 73–80%)] than nondrinkers [83% (95% CI 82–84%); RR: 0.93 (95% CI: 0.89–0.97)]. If on ART, there was no association between alcohol use and viral suppression; however, very-high-level users were less likely to be suppressed [RR: 0.80 (95% CI: 0.68–0.94)] versus nondrinkers. On a population level, viral suppression was 38% (95% CI: 36–41%) among drinkers and 44% (95% CI: 43–45%) among nondrinkers [RR: 0.87 (95% CI 0.82–0.94)], an association seen at all drinking levels. Conclusion: Alcohol use was associated with lower viral suppression; this may be because of decreased HIV diagnosis and ART use.