Project description:IntroductionOral tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis (PrEP), introduced into South Africa (SA) in 2016, has increasingly become part of HIV prevention standard of care. Given the urgent need for increased HIV prevention efforts for young women in SA, we conducted an implementation study to explore oral PrEP initiation and adherence, and the impact of oral PrEP on HIV incidence in this group.MethodsThis prospective cohort study (CAPRISA 082) was conducted at two sites (urban and rural) in KwaZulu-Natal, between March 2016 and February 2018. HIV-negative, sexually active women, aged 18-30 years, were enrolled and followed for approximately 10 months. Oral PrEP was offered as part of a comprehensive HIV prevention package. Adherence to oral PrEP was measured using pill counts and tenofovir-diphosphate (TFV-DP) levels. Characteristics of oral PrEP initiators versus non-initiators were compared using risk ratios. HIV incidence rates were measured using Poisson regression.ResultsOf 425 women enrolled, 262 (62%) initiated oral PrEP. Uptake was significantly higher at the rural site compared to the urban site (78% [n = 203/259] vs. 36% [n = 59/166], respectively, p-value<0.001). Approximately 25% and 50% had stopped using oral PrEP by 3 and 12 months post-initiation, respectively. Median pill count adherence was 90% (interquartile range: 81-97%); however, TFV-DP was only detected in 13% of samples tested, that is 56/431 samples from 97 (37%) participants who initiated oral PrEP. In total, 11 women seroconverted yielding an HIV incidence rate of 2.81 per 100 person-years (95% confidence interval: 1.40-5.03). Nine of 11 seroconverters had initiated oral PrEP; however, all showed drug levels equivalent to taking one to zero tablets per week. Among women who initiated oral PrEP, >50% had discontinued using oral PrEP by study end, with side effects, such as diarrhoea, nausea, headaches and rash, being the most frequent reason for discontinuation.ConclusionsDespite moderate oral PrEP initiation and high pill count adherence, adherence as measured by TFV-DP levels was low and early discontinuation was high. The overall HIV incidence rate was high underscoring the critical need to address barriers to oral PrEP initiation, adherence and continued use, as well as expanding HIV prevention options for young women.

Project description:BackgroundPregnant women in settings with high HIV prevalence are at increased risk of HIV acquisition and subsequent vertical transmission. We implemented and evaluated a novel programme to provide pre-exposure prophylaxis (PrEP) in maternal and child health clinics in Kenya.MethodsIn collaboration with Kisumu County Department of Health, we integrated PrEP delivery within 16 maternal and child health clinics in Kisumu County (Kenya). Women and girls older than 15 years seeking maternal and child health services who tested HIV negative at that visit or within a month and were willing to receive PrEP counselling were interviewed to assess for HIV behavioural risk factors and offered PrEP. Correlates of PrEP initiation and continuation were assessed using Poisson regression in univariate and multivariate analyses. Potential correlates included in our analyses were age, marital status, marriage type, whether pregnant or post partum, gestational age (if pregnant), and HIV risk factors in the previous 6 months. Reasons for the decision to discontinue after having decided to initiate PrEP were evaluated. Women who initiated PrEP were followed up 1 month, 3 months, and 6 months after initiation.FindingsBetween Nov 20, 2017, and June 13, 2018, 9376 pregnant and post-partum women were assessed for behavioural risk factors and willingness to initiate PrEP. Overall, 2030 (21·7%) initiated PrEP, and 2027 had the status of their partner captured (153 [79·3%] of 193 women with partners living with HIV, 1178 [37·2%] of 3165 women with partners of unknown HIV status, and 696 [11·6%] of 5997 women with HIV-negative partners). Predictors of PrEP initiation in the multivariate analysis were: being younger than 24 years (adjusted prevalence ratio 1·14, 95% CI 1·02-1·28); having a partner living with HIV (6·96, 5·46-8·89) or of unknown HIV status (3·08, 2·50-3·81); gestational age of less than 26 weeks (1·22, 1·02-1·47); having been diagnosed or treated for a sexually transmitted infection (1·57, 1·20-2·06); having been forced to have sex (1·82, 1·38-2·42); having experienced intimate partner violence during the previous 6 months (1·65, 1·10-2·48); having shared needles while engaging in injection drug use (2·43, 1·69-3·50); and recurrent use of post-exposure prophylaxis (1·96, 1·36-2·82). Overall, 786 (38·7%) of 2030 women who initiated PrEP continued use after the first month, with 104 (68·0%) of 153 women who had a partner living with HIV continuing use. Having a partner living with HIV was the only predictor of PrEP continuation at 1 month in the multivariable model (1·98, 1·54-2·55). Frequent reasons for discontinuation were side effects and low HIV risk perception. No incident HIV infection was reported among women on PrEP.InterpretationMany women attending maternal and child health clinics had risk factors for HIV and elected to use PrEP, indicating that routinely accessed maternal and child health clinics can be an effective platform for PrEP delivery for young women. As PrEP awareness rises, PrEP provision in routine clinical settings such as maternal and child health facilities might contribute to decreased HIV incidence among young women.FundingUS Department of State.

Project description:Bone histology of crown-group birds is a research topic of great interest, permitting insight into the evolution of remarkably high growth rates in this clade and variation across the altricial-precocial spectrum. In this study, we describe microanatomical characteristics of the humerus and femur in partial growth series from 14 crown group birds representing ten major clades (Struthioniformes, Galliformes, Apodiformes, Columbiformes, Charadriiformes, Accipitriformes, Strigiformes, Psittaciformes, Falconiformes, and Passeriformes). Our goals were to: (1) describe the microanatomy of each individual; (2) make inter-and intra-taxonomic comparisons; (3) assess patterns that correspond with developmental mode; and (4) to further parse out phylogenetic, developmental, and functional constraints on avian osteological development. Across taxa, the femoral and humeral tissue of neonates can be broadly characterized as highly-vascularized, disorganized woven bone with great variation in cortical thickness (inter-and intrataxonomically, within an individual specimen, and within a single section). The tissue of precocial chicks is relatively more mature at hatching than in altricial, but other categories along the developmental spectrum were less easy to distinguish, thus we were unable to identify a definitive histological proxy for developmental mode. We did not find evidence to support hypotheses that precocial chicks exclusively have thicker cortices and more mature bone in the femur than the humerus at time of hatching; instead, this is a characteristic of nearly all taxa (regardless of developmental mode), suggesting deep evolutionary origins and the effects of developmental channeling. Bone tissue in adults exhibited unexpected variation, corresponding to differences in body size. Large-bodied birds have cortices of fibrolamellar bone, but organization of tissue increases and vascularity decreases with diminishing body size. The outer circumferential layer (OCL) also appears at earlier growth stages in small-bodied taxa. Thus, while the OCL is indicative of a cessation of appositional growth it is not always indicative of cortical maturity (that is, maximum organization of bony tissue for a given taxon). Small size is achieved by truncating the period of fast growth; manipulation of the timing of offset of bone growth is therefore an important factor in changing growth trajectories to alter adult body size.

Project description:BackgroundDaily oral pre- or post-exposure prophylaxis (PrEP or PEP) is highly effective in preventing HIV infection. However, many people find it challenging to adhere to a daily oral regimen. Chemoprophylaxis with single oral doses of antiretroviral drugs taken before or after sex may better adapt to changing or unanticipated sexual practices and be a desirable alternative to daily PrEP or PEP. We investigated willingness to use a single oral pill before or after sex among men who have sex with men (MSM) and assessed the biological efficacy of a potent antiretroviral combination containing elvitegravir (EVG), emtricitabine (FTC), and tenofovir alafenamide (TAF).MethodsData on willingness to use single-dose PrEP or PEP were obtained from the 2017 cycle of the American Men's Internet Survey (AMIS), an annual online behavioral surveillance survey of MSM in the United States. Antiretroviral drug levels were measured in humans and macaques to define drug distribution in rectal tissue and identify clinically relevant doses for macaque modeling studies. The biological efficacy of a single dose of FTC/TAF/EVG as PrEP or PEP was investigated using a repeat-challenge macaque model of rectal HIV infection.FindingsThrough pharmacokinetic assessment in humans and macaques we found that EVG penetrates and concentrates in rectal tissues supporting its addition to FTC/TAF to boost and extend chemoprophylactic activity. Efficacy estimates for a single oral dose given to macaques 4h before or 2h after SHIV exposure was 91•7%[35•7%-98•9%] and 100%, respectively, compared to 80•1%[13•9%-95•4%] and 64•6%[-19•4%-89•5%] when single doses were given 6 and 24h post challenge, respectively. A two-dose regimen at 24h and 48h after exposure was also protective [77•1%[1•7%-94•7%].InterpretationInformed by user willingness, human and macaque pharmacokinetic data, and preclinical efficacy we show that single-dose prophylaxis before or after sex is a promising HIV prevention strategy. Carefully designed clinical trials are needed to determine if any of these strategies will be effective in humans.FundingFunded by CDC intramural funds, CDC contract HCVJCG2-2016-03948 (to CFK), and a grant from the MAC AIDS Fund and by the National Institutes of Health [P30AI050409] - the Emory Center for AIDS Research (to MZ and TS).

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Uptake of and intention to use oral pre-exposure prophylaxis for HIV among pregnant and post-natal women in Eswatini: a cross-sectional survey

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