Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

Background Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification and the effectiveness of partner notification has not been evaluated in developing countries. Methods Individuals with newly diagnosed HIV infection presenting to STI clinics in Lilongwe, Malawi were randomized to one of three methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly. Results 240 index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20/82 (24%; 95% CI 15 – 34%) partners returned in the passive referral arm, 45/88 (51%; 95% CI 41 – 62%) in the contract referral arm, and 42/82 (51%; 95% CI 40 – 62%) in the provider referral arm (p<0·001). Among returning partners (n=107), 67 (64%) of were HIV-infected with 54 (81%) newly diagnosed. Discussion This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among STI clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.

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Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.

BackgroundPatients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission.MethodsWe pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site.ResultsWe compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18–29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5–50% of participants, substantially decreasing the number needing testing.ConclusionOur targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.