Clinical roundup

Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy. We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors. Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10,000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner. The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

HIV transmission efficiency is greatly increased when viruses are transmitted at virological synapses formed between infected and uninfected cells. We have previously shown that virological synapses formed between HIV-pulsed mature dendritic cells (DCs) and uninfected T cells contain interdigitated membrane surfaces, with T cell filopodia extending toward virions sequestered deep inside invaginations formed on the DC membrane. To explore membrane structural changes relevant to HIV transmission across other types of intercellular conjugates, we used a combination of light and focused ion beam scanning electron microscopy (FIB-SEM) to determine the three-dimensional (3D) architectures of contact regions between HIV-1-infected CD4(+) T cells and either uninfected human CD4(+) T cells or human fetal astrocytes. We present evidence that in each case, membrane extensions that originate from the uninfected cells, either as membrane sheets or filopodial bridges, are present and may be involved in HIV transmission from infected to uninfected cells. We show that individual virions are distributed along the length of astrocyte filopodia, suggesting that virus transfer to the astrocytes is mediated, at least in part, by processes originating from the astrocyte itself. Mechanisms that selectively disrupt the polarization and formation of such membrane extensions could thus represent a possible target for reducing viral spread.

Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV.