Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.

Joint VCT prompted sustained but imperfect condom use in HIV discordant couples. Biological markers were insensitive but provided evidence for a significant under-reporting of unprotected sex. Strategies that encourage truthful reporting of sexual behavior and sensitive biological markers of exposure are urgently needed. The impact of prevention programs should be assessed with both behavioral and biological measures.

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To determine the response of the small intestinal mucosa to environmental conditions, we studied changes in mucosal architecture and function in a longitudinal cohort study in African adults. Over three consecutive years, 238 adults submitted monthly stool samples for parasitologic and bacteriologic analysis and underwent an annual endoscopic jejunal biopsy for mucosal morphometry. Absorption and permeability assays were performed on the same day as the enteroscopy. Variation in mucosal architecture and function was correlated with environmental factors and stool microbiology. The whole cohort had structural and functional evidence of tropical enteropathy, but structure and function were only weakly correlated. There were marked changes over time, and seasonal variation was observed in villous height (16%), xylose recovery (16%), and permeability (28%). Asymptomatic intestinal infections were common. Enteropathy was more severe in participants with Citrobacter rodentium or hookworm ova in the stool sample taken one month before the investigations were performed.

Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment.

BackgroundMost new HIV infections in Africa are acquired from cohabiting heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT) is an effective prevention strategy for this group. We present our experience with a community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka, Zambia.MethodsInfluence Network Agents (INAs) from the health, religious, non-governmental, and private sectors were trained to invite couples for CVCT. Predictors of successful promotion were identified using a multi-level hierarchical analysis.ResultsIn 4 months, 9,900 invitations were distributed by 61 INAs, with 1,411 (14.3%) couples requesting CVCT. INAs in Rwanda distributed fewer invitations (2,680 vs. 7,220) and had higher response rates (26.9% vs. 9.6%), than INAs in Zambia. Context of the invitation event, including a discreet location such as the INA's home (OR 3.3–3.4), delivery of the invitation to both partners in the couple (OR 1.6–1.7) or to someone known to the INA (OR 1.7–1.8), and use of public endorsement (OR 1.7–1.8) were stronger predictors of success than INA or couple-level characteristics.ConclusionPredictors of successful CVCT promotion included strategies that can be easily implemented in Africa. As new resources become available for Africans with HIV, CVCT should be broadly implemented as a point of entry for prevention, care and support.

Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX.ConclusionsThe optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.

: Many married African adults do not have high-risk profiles, nor realize that only 1 may be HIV positive. Active and sustained promotion is needed to encourage all couples to be jointly tested and counseled.