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Background: With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors associated with leading causes of death among people living with HIV/AIDS (PLWH), such as tobacco smoking, has increased. Tobacco use is highly prevalent among PLWH, especially in southern Africa, where HIV is heavily concentrated, and many people who smoke would like to quit but are unable to do so without assistance. SBIRT (Screening, Brief Intervention and Referral to Treatment) is a well-established evidence-based approach successful at supporting smoking cessation in a variety of settings. Varenicline is efficacious in supporting smoking cessation. We intend to assess the effectiveness of SBIRT and varenicline on smoking cessation among PLWH in Botswana and the effectiveness of our implementation., Methods: BSMART (Botswana Smoking Abstinence Reinforcement Trial) is a stepped-wedge, cluster randomized, hybrid Type 2 effectiveness-implementation study guided by the RE-AIM framework, to evaluate the effectiveness and implementation of an SBIRT intervention consisting of the 5As compared to an enhanced standard of care. SBIRT will be delivered by trained lay health workers (LHWs), followed by referral to treatment with varenicline prescribed and monitored by trained nurse prescribers in a network of outpatient HIV care facilities. Seven hundred and fifty people living with HIV who smoke daily and have been receiving HIV care and treatment at one of 15 health facilities will be recruited if they are up to 18 years of age and willing to provide informed consent to participate in the study., Discussion: BSMART tests a scalable approach to achieve and sustain smoking abstinence implemented in a sustainable way. Integrating an evidence-based approach such as SBIRT, into an HIV care system presents an important opportunity to establish and evaluate a modifiable cancer prevention strategy in a middle-income country (MIC) setting where both LHW and non-physician clinicians are widely used. The findings, including the preliminary cost-effectiveness, will provide evidence to guide the Botswanan government and similar countries as they strive to provide affordable smoking cessation support at scale., Clinical Trial Registration: NCT05694637 Registered on 7 December 2022 on clinicaltrials.gov, https://clinicaltrials.gov/search?locStr=Botswana&country=Botswana&cond=Smoking%20Cessation&intr=SBIRT., (© 2024. The Author(s).)

Background: Adolescent girls and young women accounted for 25% of all new HIV infections despite representing only 10% of the population in Sub Saharan Africa. PEPFAR has launched the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) initiative, a comprehensive HIV prevention program including PrEP services. Among adolescent girls and young women, PrEP adherence is currently sub-optimal. Tailored strategies for adolescent girls and young women to improve access and use of PrEP delivery are urgently needed to maximise its potential. Recommended interventions include peer-delivered interventions using mobile technology. However, data on the feasibility and acceptability of this approach is limited for SSA., Objectives: We assessed the feasibility and perceived acceptability of providing mHealth peer-delivered interventions to support PrEP services among adolescent girls and young women in Botswana., Methods: This cross-sectional study included HIV-negative women aged 18-24 years old seeking health services at DREAMS-supported facilities. Participants completed a survey assessing the feasibility and perceived acceptability of the mHealth peer-delivered interventions, which included the Acceptability of Intervention Measure (AIM). Descriptive analyses were performed., Results: A total of 131 participated in the study. Overall, 89% owned a mobile phone (feasibility). There was no difference in cell phone ownership between participants from rural and urban settings. Among participants, 85% reported interest in participating in a mHealth peer-delivered intervention if it was available to them. Regarding perceived acceptability for mHealthpeer support groups for PrEP, the average score on the AIM was 3.8 out of 5 (SD = 0.8)., Conclusion: mHealthpeer-delivered interventions appear to be feasible and perceived acceptable among adolescent girls and young women in Botswana. This modality should be incorporated into PEPFAR's programmatic toolkit of implementation strategies to improve PrEP services.

Southern Africa continues to be the epicenter of the HIV/AIDS epidemic. This HIV-1 subtype C epidemic has a predominantly heterosexual mode of virus transmission and high (>15%) HIV prevalence among adults. The epidemiological dynamics of the HIV-1C epidemic in southern Africa are still poorly understood. Here, we aim at a better understanding of HIV transmission dynamics by analyzing HIV-1 subtype C sequences from Mochudi, a peri-urban village in Botswana. HIV-1C env gene sequences (gp120 V1C5) were obtained through enhanced household-based HIV testing and counseling in Mochudi. More than 1200 sequences were generated and phylogenetically distinct sub-epidemics within Mochudi identified. The Bayesian birth-death skyline plot was used to estimate the effective reproductive number, R, and the timing of virus transmission, to classify sub-epidemics as "acute" (those with recent viral transmissions) or "historic" (those without recent viral transmissions). We identified two of the 15 sub-epidemics as "acute." The median estimates of R among the clusters ranged from 0.72 to 1.77. The majority of HIV lineages, 11 out of 15 clusters with 5+ members, appear to have been introduced to Mochudi between 1996 and 2002. The median peak duration of viral transmissions was 7.1 years (range 2.9-9.7 years). The median life span of identified HIV sub-epidemics, i.e., the time between the inferred epidemic origin and its most recent sample, was 13.1 years (range 10.2-22.1 years). Most viral transmissions within the sub-epidemics occurred between 1997 and 2007. The time period during which infected people are infectious appears to have decreased since the introduction of the national ART program in Botswana. Real-time HIV genotyping and breaking down local HIV epidemics into phylogenetically distinct sub-epidemics may help to reveal the structure and dynamics of HIV transmission networks in communities, and aid in the design of targeted interventions for members of the acute sub-epidemics that likely fuel local HIV/AIDS epidemics., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: It would be useful to understand which populations are not reached by home-based HIV-1 testing and counselling (HTC) to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission., Methods: We present the results of a baseline home-based HTC (HBHTC) campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north-eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN) estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS-IV). Analyzed data and references were stratified by age and gender., Results: A total of 6238 age-eligible residents were tested for HIV-1; 1247 (20.0%; 95% CI 19.0 to 21.0%) were found to be HIV positive (23.7% of women vs. 13.4% of men). HIV-1 prevalence peaked at 44% in 35- to 39-year-old women and 32% in 40- to 44-year-old men. A lower HIV prevalence rate, 10.9% (95% CI 9.5 to 12.5%), was found among individuals tested for the first time. A significant gender gap was evident in all analyzed subsets. The existing HIV transmission network was analyzed by combining phylogenetic mapping and household structure. Between 62.4 and 71.8% of all HIV-positive individuals had detectable virus. When compared with the UN and BAIS-IV estimates, the proportion of men missed by the testing campaign (48.5%; 95% CI 47.0 to 50.0%) was significantly higher than the proportion of missed women (14.2%; 95% CI 13.2 to 15.3%; p<0.0001). The estimated proportion of missed men peaked at about 60% in the age group 30 to 39 years old. The proportions of missed women were substantially smaller, at approximately 28% within the age groups 30 to 34 and 45 to 49 years old., Conclusions: The HBHTC campaign seems to be an efficient tool for reaching individuals who have never been tested previously in southern African communities. However, about half of men from 16 to 64 years old were not reached by the HBHTC, including about 60% of men between 30 and 40 years old. Alternative HTC strategies should be developed to bring these men to care, which will contribute to reduction of HIV incidence in communities.

Background: Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities., Methods: To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010-2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits., Results: The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters., Conclusions: The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and combined intervention packages.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number. Author summary: Epidemic control and forecasting relies on accurate quantification of transmission and recovery dynamics. This quantification is achievable through the analysis of phylogenetic relationships among pathogen strains obtained from infected individuals. As a key analytical tool for such inference, we concentrate on the study of the episodic birth-death-sampling (EBDS) models. These models define a probability distribution on time-calibrated phylogenies that enable estimation of time-varying rates of pathogens' transmission, recovery, and sampling. Advances in sequencing technology, however, have led to an increasing amount of genetic data collected from these pathogens. Consequently, the traditional computational methods for analyzing these large-scale data under EBDS models have become inadequate due to their high computational load. We aimed to break this computational bottleneck by developing a new approach, based on the Hamiltonian Monte Carlo sampling, that considerably accelerates inference of all rate parameters compared to the traditional random-walk Metropolis-Hasting method. Our method greatly improves the ability to explore the complex distributions that arise when we want to understand disease dynamics at a more granular temporal resolution. This advancement delivers value to public health as it helps rapid data-driven decision-making during outbreaks and enhances our understanding of the spread of infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana. Methods: A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019–2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups. Results: A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38–48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate – 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12–0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported. Conclusion: We report high rates of PDR and ADR in ART-experienced and ARTnaïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV- 1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success. [ABSTRACT FROM AUTHOR]

Background Although Botswana has made great progress in expanding human immunodeficiency virus (HIV) testing, men are less likely to be tested for HIV and test at a later stage compared with women. For Botswana to increase HIV testing coverage among men, HIV self-testing (HIVST) may be a promising supplement to standard, healthcare facility-based HIV testing. We conducted a pilot test of the feasibility and acceptability of HIVST for men of middle-to-upper socioeconomic status in Botswana. Methods Thirty-five men were recruited through 4 workplaces (banking sector). Wellness officers emailed all potentially eligible male employees about the opportunity to participate. Men were surveyed at baseline and follow-up on basic sociodemographic characteristics, HIV testing history, HIV stigma, use of the HIVST kit (at follow-up), and confirmatory testing and linkage to care if a preliminary positive result is obtained (at follow-up). Results All 35 men used the kit. The proportion who agreed with the statement that getting tested for HIV helps people feel better increased significantly from 80.7% at baseline to 100% at follow-up. In open-ended questions, men described the advantages of HIVST, including improved privacy and convenience, lowered HIV stigma, and enhanced control over testing. Concerns about HIVST included potential negative mental health consequences owing to not receiving pretest and posttest counseling, and not linking to care after a reactive result. Conclusions Results suggest that an intervention in which HIVST is discrete, private, and under men's control can help overcome stigma around HIV testing, resulting in a greater number of men tested. [ABSTRACT FROM AUTHOR]

Background: The majority of childhood blindness causes in low-income countries are treatable or avoidable. Parents or guardians are responsible for making decisions regarding a child's eye care. Understanding parents' awareness and perception of eye problems in crucial in helping to know parents' eye care-seeking behavior. Objective: To determine parental knowledge, attitudes and practice regarding child eye health. Methods: Seven focus groups were carried out in Northwest Ethiopia on knowledge, attitude and practice of parents towards child eye health. Their responses were tape-recorded and later transcribed. A thematic phenomenological approach was used for the analysis. Result: Seventy-one parents participated in the focus groups. Participants were aware of common eye problems like trachoma, trauma, and glaucoma. However, they were unaware of the causes and etiologies of childhood blindness. Participants perceived that eye problems could be treated with hygiene and food, and often held misconceptions about the cause of strabismus and utilization of wearing spectacles. Conclusion: The study revealed that parents are often unaware of the causes and etiologies of common childhood eye diseases, which has downstream effects on health-seeking behavior. Health promotion efforts, potentially through mass and social media, could be helpful to raise awareness, coupled with training of health professionals at primary and secondary health facility levels. [ABSTRACT FROM AUTHOR]

Background: In countries such as Eswatini, where there is a high HIV prevalence and low male circumcision the World Health Organization and the Joint United Nations Programme for HIV/AIDS recommend infant and adult circumcision be implemented. The aim of this study was to assess the knowledge, attitudes and acceptability of voluntary medical male circumcision amongst males attending high school in Eswatini. Methods: An observational cross-sectional study was conducted during February and March of 2018 amongst 407 young males (15–21 years) attending Form 4, in nine high schools in the Shiselweni region of Eswatini using a self-administered questionnaire of 42 close ended questions. Sociodemographic details, circumcision status, acceptance of voluntary medical male circumcision, knowledge and attitude scores analysed in Stata® 14 statistical software were described using frequencies, medians and ranges respectively. Bivariate and multivariate linear regression was used to assess the impact of independent variables on circumcision status and acceptance of voluntary medical male circumcision. The level of statistical significance was p < 0.05. Results: Amongst the 407 high school-going males, 48.98% (n = 201) reported being circumcised. The majority of the adolescents (75.74%; n = 306) were knowledgeable about voluntary medical male circumcision. However, an even larger majority (84.90% (n = 343) had a negative attitude towards it. In the multivariate logistic regression analysis, having parented their own children (aOR: 3.55; 95%CI: 1.2–10.48), and having circumcised friends (aOR: 3.99; 95%CI: 1.81–8.84) were significantly associated with being circumcised. Neither knowledge nor attitude were associated with the acceptability of voluntary medical male circumcision. Conclusion: In Eswatini male high school students are knowledgeable about voluntary medical male circumcision but have a negative attitude towards it. Having parented their own children, and having circumcised friends influenced being circumcised. [ABSTRACT FROM AUTHOR]

Since the 1980s studies on men have frequently utilized Connell's framework of hegemonic masculinities. We critically appraise this framework in the context of a population-based HIV pre-exposure prophylaxis study in Eswatini. Our findings highlight that men confidently show variation in their behavior and choices, which manifest across different men and within the same men acting in particular situations and over the life course. This led us to interrogate the hegemonic masculinities framework on the following grounds: Men's choices and behavior do not seem to fit the model of aspiring to a hegemonic ideal; the delineation of masculine traits as hegemonic or subordinate remain vague in terms of "responsibility," "fidelity," and "consideration for others"; the binary gender concept underpinning hegemonic masculinities seems outdated. Building on the work of Hirsch and Kachtan, we propose cultural repertoires as an alternative framework which also bridges the gender divide. [ABSTRACT FROM AUTHOR]

The Population-based HIV Impact Assessment (PHIA) is an ongoing project that conducts nationally representative HIV-focused surveys for measuring national and regional progress toward UNAIDS' 90-90-90 targets, the primary strategy to end the HIV epidemic. We believe the PHIA survey offers a unique opportunity to better understand the key factors that drive the HIV epidemics in the most affected countries in sub-Saharan Africa. In this article, we propose a novel causal structural learning algorithm to discover important covariates and potential causal pathways for 90-90-90 targets. Existing constraint-based causal structural learning algorithms are quite aggressive in edge removal. The proposed algorithm preserves more information about important features and potential causal pathways. It is applied to the Malawi PHIA (MPHIA) dataset and leads to interesting results. For example, it discovers age and condom usage to be important for female HIV awareness; the number of sexual partners to be important for male HIV awareness; and knowing the travel time to HIV care facilities leads to a higher chance of being treated for both females and males. We further compare and validate the proposed algorithm using BIC and using Monte Carlo simulations, and show that the proposed algorithm achieves improvement in true positive rates in important feature discovery over existing algorithms. for this article are available online. [ABSTRACT FROM AUTHOR]

The retinoid (10mM) increased viral reactivation mediated by IL-15 to a similar extent as HODHBt (100mM) but unlike HODHBt, specifically promoted cell death of latently infected cells compared to controls when combined with IL-15. This indicates that the retinoid is able to reactivate latent HIV through a mechanism mediated by IL-15 but not directly dependent on STAT5 phosphorylation. Among the clinically relevant latency reversing agents (LRA) under investigation, IL-15 or the IL-15 superagonist N-803 have been shown to reactivate latent HIV I ex vivo i and I in vivo i . [Extracted from the article]

Introduction: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. Design: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. Methods: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16–49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. Results: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16–24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. Conclusion: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services. [ABSTRACT FROM AUTHOR]

Introduction: Men are missing along the HIV care continuum. However, the estimated proportions of men in sub‐Saharan Africa meeting the UNAIDS 95‐95‐95 goals vary substantially between studies. We sought to estimate proportions of men meeting each of the 95‐95‐95 goals across studies in sub‐Saharan Africa, describe heterogeneity, and summarize qualitative evidence on factors influencing care engagement. Methods: We systematically searched PubMed and Embase for peer‐reviewed articles published between 1 January 2014 and 16 October 2020. We included studies involving men ≥15 years old, with data from 2009 onward, reporting on at least one 95‐95‐95 goal in sub‐Saharan Africa. We estimated pooled proportions of men meeting these goals using DerSimonion‐Laird random effects models, stratifying by study population (e.g. studies focusing exclusively on men who have sex with men vs. studies that did not), facility setting (healthcare vs. community site), region (eastern/southern Africa vs. western/central Africa), outcome measurement (e.g. threshold for viral load suppression), median year of data collection (before vs. during or after 2017) and quality criteria. Data from qualitative studies exploring barriers to men's HIV care engagement were summarized using meta‐synthesis. Results and discussion: We screened 14,896 studies and included 129 studies in the meta‐analysis, compiling data over the data collection period. Forty‐seven studies reported data on knowledge of serostatus, 43 studies reported on antiretroviral therapy use and 74 studies reported on viral suppression. Approximately half of men with HIV reported not knowing their status (0.49 [95% CI, 0.41–0.58; range, 0.09–0.97]) or not being on treatment (0.58 [95% CI, 0.51–0.65; range, 0.07–0.97]), while over three‐quarters of men achieved viral suppression on treatment (0.79 [95% CI, 0.77–0.81; range, 0.39–0.97]. Heterogeneity was high, with variation in estimates across study populations, settings and outcomes. The meta‐synthesis of 40 studies identified three primary domains in which men described risks associated with engagement in HIV care: perceived social norms, health system challenges and poverty. Conclusions: Psychosocial and systems‐level interventions that change men's perceptions of social norms, improve trust in and accessibility of the health system, and address costs of accessing care are needed to better engage men, especially in HIV testing and treatment. [ABSTRACT FROM AUTHOR]

The shape of phylogenetic trees can be used to gain evolutionary insights. A tree's shape specifies the connectivity of a tree, while its branch lengths reflect either the time or genetic distance between branching events; well-known measures of tree shape include the Colless and Sackin imbalance, which describe the asymmetry of a tree. In other contexts, network science has become an important paradigm for describing structural features of networks and using them to understand complex systems, ranging from protein interactions to social systems. Network science is thus a potential source of many novel ways to characterize tree shape, as trees are also networks. Here, we tailor tools from network science, including diameter, average path length, and betweenness, closeness, and eigenvector centrality, to summarize phylogenetic tree shapes. We thereby propose tree shape summaries that are complementary to both asymmetry and the frequencies of small configurations. These new statistics can be computed in linear time and scale well to describe the shapes of large trees. We apply these statistics, alongside some conventional tree statistics, to phylogenetic trees from three very different viruses (HIV, dengue fever and measles), from the same virus in different epidemiological scenarios (influenza A and HIV) and from simulation models known to produce trees with different shapes. Using mutual information and supervised learning algorithms, we find that the statistics adapted from network science perform as well as or better than conventional statistics. We describe their distributions and prove some basic results about their extreme values in a tree. We conclude that network science-based tree shape summaries are a promising addition to the toolkit of tree shape features. All our shape summaries, as well as functions to select the most discriminating ones for two sets of trees, are freely available as an R package at http://github.com/Leonardini/treeCentrality. [ABSTRACT FROM AUTHOR]

Background: HIV testing among men is paramount in the prevention, diagnosis, and treatment of HIV. There is limited literature in understanding the socio-economic and demographic factors associated with never having tested for HIV among sexually active men aged 15 - 54 across the four administrative regions of Uganda. The purpose of this study is to investigate the socio-economic and demographic factors associated with never having tested for HIV among sexually active men aged 15 - 54 across the four administrative regions in the country. Methods: The study used a cross-sectional research design to examine factors associated with never having tested for HIV among 4,168 sexually active men (15 - 54 years) across four administrative regions of Uganda using data from 2016 Uganda Demographic and Health Survey (UDHS). Frequency distributions, Pearson chi-square tests, and multivariable logistic regression were used to establish the association between never having tested for HIV among sexually active men (15 - 54 years) and selected independent variables across regions. Results: About 20% of sexually active men (15 - 54 years) never tested for HIV across regions of the country. The major correlates amidst variability of never testing for HIV among sexually active men across regions were; educational level and marital status. Age, religious status, wealth quintile, worked in the last 12 months, circumcised, and one sexual partner in the last 12 months were only correlates of never having tested for HIV among respondents in particular regions of the country. Conclusion: Findings in the study suggest promotion of male education, and suggest further investigation into the relationship between HIV non-testing among sexually active men (15 - 54 years) and being married across regions of the country. The study also proposes appreciation of regional differences in the outcome of HIV non-testing and suggests that efforts be focused on addressing regional differences in order to attain high HIV testing among sexually active men (15 - 54 years) across regions of Uganda, and thus reduce HIV related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Older adults (50 years and over) are still sexually active and therefore vulnerable to unplanned pregnancy, infection of STIs and HIV, yet there are no programmes in place to cater for their family planning needs. The objective of the study is to show how some socio-economic characteristics of older adults influence their family planning (FP) use. The study used a stratified random sampling design where four health districts (two urban and two rural) were purposively selected and the sample size of 444 older adult women allocated to the districts using proportional allocation to size. Snowball technique was used in identifying respondents. The multinomial logistic regression analysis reveals that while age, marital status, educational qualification, employment status, menopausal status, district and desire for another child jointly significantly predict FP use, only menopausal status and desire for another child individually significantly (p < 0.01) predict FP use. Older adult women who desired another child were significantly (p < 0.01) 7.5 times more likely to use family planning (FP) methods than those who do not want another child. The postmenopausal older adult women were less likely to use FP methods than those in their premenopausal state (OR = 0.13). Women with no schooling were less likely to use FP methods than those with degree/professional qualifications. Single and married women were less likely to use FP methods than the divorced/widowed/separated. The study recommends the promotion of education and training on FP use among the older adult women that will take into consideration their menopausal status and desire for another child. The training should be home-based. [ABSTRACT FROM AUTHOR]

In discussions about sex work, two dominant views are evident: Sex workers freely choose to sell sex as a means of earning an income or sex workers are victims of circumstances, driven into the sex industry through coercion or dire poverty. Both these views oversimplify the actuality of sex work. Sex workers themselves also at times oscillate between these two positions, but in this article we demonstrate how they are able, to some extent, to open up discursive spaces between these two extremes. However, just as sex workers are neither entirely passive victims nor entirely free agents in their lived experience, so too they are neither entirely passive channels for larger social discourses about their profession, nor entirely free to voice an authentic, first-hand account of what sex work “really” is. To explore this discursive entanglement, we spoke to five sex workers in Johannesburg and describe the ways in which they were able to both take on board, and to challenge, a variety of different discourses in order to talk about themselves as simultaneously agentic and constrained in what they can do. [ABSTRACT FROM AUTHOR]

Introduction: The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. Methods: A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. Results: Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2–13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4–83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3–81.2) and participants in care 76.2% (95%CI: 72.4–79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9–96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6–92.4) and was not statistically different by sex (p = 0.40). Conclusions: Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults. [ABSTRACT FROM AUTHOR]

Background: Given the rampant HIV epidemic among men who have sex with men (MSM) in Chengdu, southwest China, Treat All policy, defined as immediate antiretroviral therapy (ART) initiation after HIV diagnosis, was implemented since 2014. Real-world research evaluating impacts of immediate ART on HIV epidemics is needed to optimize policy-making as national and international guidelines have been lowering ART eligibility threshold. The purpose of this study is to: assess temporal trends of the HIV epidemic and impacts of Treat All policy among MSM; and lay foundation for HIV-related policy evaluation using longitudinal routine data from health information systems.Methods: Data used in this study were HIV sentinel seroprevalence, annual reported HIV cases and ART coverage rate among MSM in Chengdu from 2008 to 2018, derived from national HIV/AIDS information system. Temporal trends of the HIV epidemic were described using Joinpoint Regression Program. Interrupted time-series method was deployed to evaluate Treat All policy.Results: HIV sentinel seroprevalence rose from 11.20% in 2008 to 17.67% in 2013 and Annual Percent Change (APC) was 8.25% (95% CI - 2.40%, 20.07%), then decreased to 5.17% in 2018 (APC = - 19.63%, 95% CI - 27.54%, - 10.86%). Newly reported HIV cases increased from 168 cases in 2008 to 1232 cases in 2015 (APC = 26.99%, 95% CI 21.32%, 32.93%), and reduced to 1014 cases in 2018 (APC = - 8.80%, 95% CI - 18.45%, 2.01%). ART coverage rate has been climbing from 11.11% in 2008 to 92.29% in 2018 and Average Annual Percent Change was 16.09% (95% CI 11.76%, 20.59%). Results of interrupted time-series models showed that compared to an annual increase of 0.87% during pre-policy period, there was a decline of 3.08% (95% CI - 0.0366%, - 0.0250%) per year of HIV sentinel seroprevalence since 2014; and compared to an annual increase of 116 cases before 2014, there was an annual drop of 158 newly reported HIV cases (95% CI - 194.87%, - 121.69%) during the post-policy period.Conclusions: Immediate ART after HIV diagnosis could potentially curb HIV transmission at population level among MSM, along with other strategies. Future assessment of HIV prevention and control policy can be carried out using routinely collected longitudinal data from health information systems. [ABSTRACT FROM AUTHOR]

Background: In a cluster-randomised trial (CRT) of combination HIV prevention (HPTN 071 (PopART)) in 12 Zambian communities and nine South African communities, carried out from 2012 to 2018, the intervention arm A that offered HIV treatment irrespective of CD4 count did not have a significant impact on population level HIV incidence. Intervention arm B, where HIV incidence was reduced by 30%, followed national guidelines that mid trial (2016) changed from starting HIV treatment according to a CD4 threshold of 500 to universal treatment. Using social science data on the 21 communities, we consider how place (community context) might have influenced the primary outcome result.Methods: A social science component documented longitudinally the context of trial communities. Data were collected through rapid qualitative assessment, interviews, group discussions and observations. There were a total of 1547 participants and 1127 observations. Using these data, literature and a series of qualitative analysis steps, we identified key community characteristics of relevance to HIV and triangulated these with HIV community level incidence.Results: Two interdependent social factors were relevant to communities' capability to manage HIV: stability/instability and responsiveness/resistance. Key components of stability were social cohesion; limited social change; a vibrant local economy; better health, education and recreational services; strong institutional presence; established middle-class residents; predictable mobility; and less poverty and crime. Key components of responsiveness were community leadership being open to change, stronger history of HIV initiatives, willingness to take up HIV services, less HIV-related stigma and a supported and enterprising youth population. There was a clear pattern of social factors across arms. Intervention arm A communities were notably more resistant and unstable. Intervention arm B communities were overall more responsive and stable.Conclusions: In the specific case of the dissonant primary outcome results from the HPTN 071 (PopART) trial, the chance allocation of less stable, less responsive communities to arm A compared to arm B may explain some of the apparently smaller impact of the intervention in arm A. Stability and responsiveness appear to be two key social factors that may be relevant to secular trends in HIV incidence. We advocate for a systematic approach, using these factors as a framework, to community context in CRTs and monitoring HIV prevention efforts.Trial Registration: ClinicalTrials.gov NCT01900977 . Registered on July 17, 2013. [ABSTRACT FROM AUTHOR]

Introduction: Facility‐based HIV testing services (HTS) have been less acceptable and accessible by adolescents, men and key populations in South Africa. Community‐based HIV counselling and testing (CBCT) modalities, including mobile unit and home‐based testing, have been proposed to decrease barriers to HIV testing uptake. CBCT modalities and approaches may be differentially acceptable to men and women based on age. Implementation of multimodal CBCT services may improve HIV testing rates among adolescents and men, and support the roll‐out of prevention services. Methods: A cross‐sectional analysis was conducted using aggregate, routine programmatic data collected from 1 October 2015 through 31 March 2017 from a multimodal, at‐scale CBCT programme implemented in 12 high‐burden districts throughout South Africa. Data collection tools were aligned to reporting standards for the National Department of Health and donor requirements. HIV testing rates (i.e. number of tests performed per 100,000 population using South African census data) and testing proportions by modality were stratified by sex, age groups and heath districts. Descriptive statistics were performed using STATA 13.0. Results: Overall, 944,487 tests were performed during the 1.5‐year testing period reported. More tests were conducted among females than males (53.6% vs. 46.4%). Overall, 8206 tests per 100,000 population (95% CI: 8190.2 to 8221.9) were performed; female‐to‐male (F:M) testing ratio was 1.11. Testing rates were highest among young women age 20 to 24 years (16,328.4; 95% CI: 16,237.9 to 16,419.1) and adolescent girls aged 15 to 19 years (12,817.0; 95% CI: 12,727.9 to 12,906.6). Home‐based testing accounted for 61.3% of HIV tests, followed by near‐home mobile unit testing (30.2%) and workplace mobile unit testing (4.7%). More women received HTS via home‐based testing (F:M ratio = 1.29), whereas more men accessed work‐place mobile testing (M:F ratio = 1.35). No sex differential was observed among those accessing near‐home mobile testing (F:M ratio = 0.98). Conclusions: Concurrent implementation of multiple, targeted CBCT modalities can reduce sex disparities in HIV testing in South Africa. Given the acceptability and accessibility of these CBCT services to adolescent girls and young women, evident from their high testing rates, leveraging community‐based services delivery platforms to increase access to HIV prevention services, including pre‐exposure prophylaxis (PrEP), should be considered. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence in Mozambique (12.6%) is one of the highest in the world, yet ~40% of people living with HIV (PLHIV) do not know their HIV status. Strategies to increase HIV testing uptake and diagnosis among PLHIV are urgently needed. Home-based HIV testing services (HBHTS) have been evaluated primarily as a 1-time campaign strategy. Little is known about the potential of repeating HBHTS to diagnose HIV infection among persons who have never been tested (NTs), nor about factors/reasons associated with never testing in a generalized epidemic setting. Methods: During 2014–2017, counselors visited all households annually in the Chókwè Health and Demographic Surveillance System (CHDSS) and offered HBHTS. Cross-sectional surveys were administered to randomly selected 10% or 20% samples of CHDSS households with participants aged 15–59 years before HBHTS were conducted during the visit. Descriptive statistics and logistic regression were used to assess the proportion of NTs, factors/reasons associated with never having been tested, HBHTS acceptance, and HIV-positive diagnosis among NTs. Results: The proportion of NTs decreased from 25% (95% confidence interval [CI]:23%–26%) during 2014 to 12% (95% CI:11% –13%), 7% (95% CI:6%–8%), and 7% (95% CI:6%–8%) during 2015, 2016, and 2017, respectively. Adolescent boys and girls and adult men were more likely than adult women to be NTs. In each of the four years, the majority of NTs (87%–90%) accepted HBHTS. HIV-positive yield among NTs subsequently accepting HBHTS was highest (13%, 95% CI:10%–15%) during 2014 and gradually reduced to 11% (95% CI:8%–15%), 9% (95% CI:6%–12%), and 2% (95% CI:0%–4%) during 2015, 2016, and 2017, respectively. Conclusions: Repeated HBHTS was helpful in increasing HIV testing coverage and identifying PLHIV in Chókwè. In high HIV-prevalence settings with low testing coverage, repeated HBHTS can be considered to increase HIV testing uptake and diagnosis among NTs. [ABSTRACT FROM AUTHOR]

This study reconstructed molecular networks of human immunodeficiency virus (HIV) transmission history in an area affected by an epidemic of multiple HIV-1 subtypes and assessed the efficacy of strengthened early antiretroviral therapy (ART) and regular interventions in preventing HIV spread. We collected demographic and clinical data of 2221 treatment-naïve HIV-1–infected patients in a long-term cohort in Shenyang, Northeast China, between 2008 and 2016. HIV pol gene sequencing was performed and molecular networks of CRF01_AE, CRF07_BC, and subtype B were inferred using HIV-TRACE with separate optimized genetic distance threshold. We identified 168 clusters containing ≥ 2 cases among CRF01_AE-, CRF07_BC-, and subtype B-infected cases, including 13 large clusters (≥ 10 cases). Individuals in large clusters were characterized by younger age, homosexual behavior, more recent infection, higher CD4 counts, and delayed/no ART (P < 0.001). The dynamics of large clusters were estimated by proportional detection rate (PDR), cluster growth predictor, and effective reproductive number (R e ). Most large clusters showed decreased or stable during the study period, indicating that expansion was slowing. The proportion of newly diagnosed cases in large clusters declined from 30 to 8% between 2008 and 2016, coinciding with an increase in early ART within 6 months after diagnosis from 24 to 79%, supporting the effectiveness of strengthened early ART and continuous regular interventions. In conclusion, molecular network analyses can thus be useful for evaluating the efficacy of interventions in epidemics with a complex HIV profile. [ABSTRACT FROM AUTHOR]

Introduction: Achieving widespread knowledge of HIV-positive status is a crucial step to reaching universal ART coverage, population level viral suppression, and ultimately epidemic control. We implemented a multi-modality HIV testing approach to identify 90% or greater of HIV-positive persons in the Botswana Combination Prevention Project (BCPP) intervention communities. Methods: BCPP is a cluster-randomized trial designed to evaluate the impact of combination prevention interventions on HIV incidence in 30 communities in Botswana. Community case finding and HIV testing that included home and targeted mobile testing were implemented in the 15 intervention communities. We described processes for identifying HIV-positive persons, uptake of HIV testing by age, gender and venue, characteristics of persons newly diagnosed through BCPP, and coverage of knowledge of status reached at the end of study. Results: Of the 61,655 eligible adults assessed in home or mobile settings, 13,328 HIV-positive individuals, or 93% of the estimated 14,270 positive people in the communities were identified through BCPP. Knowledge of status increased by 25% over the course of the study with the greatest increases seen among men (37%) as compared to women (19%) and among youth aged 16–24 (77%) as compared to older age groups (21%). Although more men were tested through mobile than through home-based testing, higher rates of newly diagnosed HIV-positive men were found through home than mobile testing. Conclusions: Even when HIV testing coverage is high, additional gains can be made using a multi-modality HIV testing strategy to reach different sub-populations who are being missed by non-targeted program activities. Men and youth can be reached and will engage in community testing when services are brought to places they access routinely. [ABSTRACT FROM AUTHOR]

Background: Knowledge of HIV status is crucial for both prevention and treatment of HIV infection. However, according to the Joint United Nations Programme on HIV/AIDS in low-and-middle-income countries (LMICs), only 10% of the population has access to HIV testing services. Home-based HIV testing and counseling (HTC) is one of the approaches which have been shown to be effective in improving access to HIV testing in LMICs. The objective of this review was to map evidence on the use of home-based HTC in LMICs.Methods: We searched PubMed, EBSCOhost, Google Scholar, Science Direct, World Health Organization library database and UNAIDS databases from January 2013 to October 2017. Eligibility criteria included articles pertaining to the use of home-based HTC in LMICs. Two reviewers independently reviewed the articles for eligibility. The following themes were extracted from the included studies: use, feasibility and effectiveness of home-based HTC on patient-centered outcomes in LMICs. The risk of bias for the included studies was assessed using mixed methods appraisal tool -version 2011.Results: A total of 855,117 articles were identified from all the databases searched. Of this, only 17 studies met the inclusion criteria after full article screening and were included for data extraction. All included studies presented evidence on the use of Home-based HTC by most age groups (18 months to 70 years) comprising of both males and females. The included studies were conducted in the following countries: Zambia, Uganda, South Africa, Kenya, Ethiopia, Malawi, Swaziland, Pakistan, and Botswana. This study demonstrated that home-based HTC was used in LMICs alongside supervised HTC intervention using different types of HTC tests kits produced by different manufacturers. This study also showed that home-based HTC was feasible, highly effective, and increased uptake of HIV testing and counseling. This study further demonstrated a highly successful usage of supervised home-based HTC by most age groups in LMICs, with majority of users being females (89.1%).Conclusion: We therefore recommend primary studies in other LMICs to determine the feasibility and use of HTC to help achieve the UNAIDS 90:90:90 targets. Interventions to improve the use of home-based HTC by males are also recommended.Trial Registration: PROSPERO registration number: CRD42017056478. [ABSTRACT FROM AUTHOR]

Background: South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. Methods: Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13–20 years (Mpumalanga province, 2011–2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. Results: The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6–7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2–6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931–1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3–2.81x10-3) per site per year. Conclusions: Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial. [ABSTRACT FROM AUTHOR]

Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa. Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004-2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of followup was the secondary outcome. Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02- 3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007-2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIVnegative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4 strata. Three-quarters of patients had VLs in their last year, and 86% of these were virally suppressed. Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale-up, testing and initiating men on ART must be a national priority. [ABSTRACT FROM AUTHOR]

Monica Sharma and colleagues discuss evidence-based approaches to improving HIV services for men in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods' development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention. [ABSTRACT FROM AUTHOR]

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Background: Voluntary medical male circumcision (VMMC) is a critical HIV prevention tool. Since 2007, sub-Saharan African countries with the highest prevalence of HIV have been mobilizing resources to make VMMC available. While implementers initially targeted adult men, demand has been highest for boys under age 18. It is important to understand how male adolescents can best be served by quality VMMC services. Methods and Findings: A systematic literature review was performed to synthesize the evidence on best practices in adolescent health service delivery specific to males in sub-Saharan Africa. PubMed, Scopus, and JSTOR databases were searched for literature published between January 1990 and March 2014. The review revealed a general absence of health services addressing the specific needs of male adolescents, resulting in knowledge gaps that could diminish the benefits of VMMC programming for this population. Articles focused specifically on VMMC contained little information on the adolescent subgroup. The review revealed barriers to and gaps in sexual and reproductive health and VMMC service provision to adolescents, including structural factors, imposed feelings of shame, endorsement of traditional gender roles, negative interactions with providers, violations of privacy, fear of pain associated with the VMMC procedure, and a desire for elements of traditional non-medical circumcision methods to be integrated into medical procedures. Factors linked to effective adolescent-focused services included the engagement of parents and the community, an adolescent-friendly service environment, and VMMC counseling messages sufficiently understood by young males. Conclusions: VMMC presents an opportune time for early involvement of male adolescents in HIV prevention and sexual and reproductive health programming. However, more research is needed to determine how to align VMMC services with the unique needs of this population. [ABSTRACT FROM AUTHOR]

Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent) viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations. [ABSTRACT FROM AUTHOR]

Background: Male circumcision (MC) reduces HIV acquisition and is a key public health intervention in settings with high HIV prevalence, heterosexual transmission and low MC rates. In Papua New Guinea (PNG), where HIV prevalence is 0.8%, there is no medical MC program for HIV prevention. There are however many different foreskin cutting practices across the country's 800 language groups. The major form exposes the glans but does not remove the foreskin. This study aimed to describe and quantify foreskin cutting styles, practices and beliefs. It also aimed to assess the acceptability of MC for HIV prevention in PNG. Methods: Cross-sectional multicentre study, at two university campuses (Madang Province and National Capital District) and at two 'rural development' sites (mining site Enga Province; palm-oil plantation in Oro Province). Structured questionnaires were completed by participants originating from all regions of PNG who were resident at each site for study or work. Results: Questionnaires were completed by 861 men and 519 women. Of men, 47% reported a longitudinal foreskin cut (cut through the dorsal surface to expose the glans but foreskin not removed); 43% reported no foreskin cut; and 10% a circumferential foreskin cut (complete removal). Frequency and type of cut varied significantly by region of origin (p < .001). Most men (72-82%) were cut between the ages of 10 - 20 years. Longitudinal cuts were most often done in a village by a friend, with circumferential cuts most often done in a clinic by a health professional. Most uncut men (71%) and longitudinal cut men (84%) stated they would remove their foreskin if it reduced the risk of HIV infection. More than 95% of uncut men and 97% of longitudinal cut men would prefer the procedure in a clinic or hospital. Most men (90%) and women (74%) stated they would remove the foreskin of their son if it reduced the risk of HIV infection. Conclusion: Although 57% of men reported some form of foreskin cut only 10% reported the complete removal of the foreskin, the procedure on which international HIV prevention strategies are based. The acceptability of MC (complete foreskin removal) is high among men (for themselves and their sons) and women (for their sons). Potential MC services need to be responsive to the diversity of beliefs and practices and consider health system constraints. A concerted research effort to investigate the potential protective effects of longitudinal cuts for HIV acquisition is essential given the scale of longitudinal cuts in PNG. [ABSTRACT FROM AUTHOR]

Examines the damage mechanics model for power-law creep and earthquake aftershock and foreshock sequences. Trimodal behavior of strain; Formation of thoroughgoing fracture; Rates of the predicted acoustic emissions.

Background: In Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of HIV cases in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. Methods: Blood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support. Results: Among the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Eight sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. Conclusion: We revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa, where ~ 25 million individuals are infected with HIV and transmission is predominantly heterosexual, there is substantial geographic variation in the severity of epidemics. This variation has yet to be explained. Here, we propose that it is due to geographic variation in the size of the high-risk group (HRG): the group with a high number of sex partners. We test our hypothesis by conducting a geospatial analysis of data from Malawi, where ~ 13% of women and ~ 8% of men are infected with HIV.Methods: We used georeferenced HIV testing and behavioral data from ~ 14,000 participants of a nationally representative population-level survey: the 2010 Malawi Demographic and Health Survey (MDHS). We constructed gender-stratified epidemic surface prevalence (ESP) maps by spatially smoothing and interpolating the HIV testing data. We used the behavioral data to construct gender-stratified risk maps that reveal geographic variation in the size of the HRG. We tested our hypothesis by fitting gender-stratified spatial error regression (SER) models to the MDHS data.Results: The ESP maps show considerable geographic variation in prevalence: 1-29% (women), 1-20% (men). Risk maps reveal substantial geographic variation in the size of the HRG: 0-40% (women), 16-58% (men). Prevalence and the size of the HRG are highest in urban centers. However, the majority of HIV-infected individuals (~75% of women, ~ 80% of men) live in rural areas, as does most of the HRG (~ 80% of women, ~ 85% of men). We identify a significant (P < 0.001) geospatial relationship linking the size of the HRG with prevalence: the greater the size, the higher the prevalence. SER models show HIV prevalence in women is expected to exceed the national average in districts where > 20% of women are in the HRG. Most importantly, the SER models show that geographic variation in the size of the HRG can explain a substantial proportion (73% for women, 67% for men) of the geographic variation in epidemic severity.Conclusions: Taken together, our results provide substantial support for our hypothesis. They provide a potential mechanistic explanation for the geographic variation in the severity of the HIV epidemic in Malawi and, potentially, in other countries in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence.Methods/design: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84% power to detect a reduction of 30% in the HIV incidence rate between surveys.Discussion: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance. [ABSTRACT FROM AUTHOR]

A Aaron, L. OAB0505 Abadie, M. OAB0106 Abbar, B. OAB0203 Abdel-Mohsen, M. PDA0207 Abdool Karim, Q. PDA0202 Abdool Karim, S. PDA0202 Abdulghani, N. PDB0105 Aberg, J. OABLB0104 Abidi, S.H. OACLB0102 [...]

ORAL ABSTRACT Pharmacological enhancement of IL?15 signaling to improve ?shock?and?kill? strategies against latent HIV J.N. Howard[sup.1] , A. Bosque[sup.1] [sup.1] George Washington University, Microbiology, Immunology, and Tropical Medicine, Washington DC, [...]

Introduction The CD4+ T-lymphocyte count is the method recommended by the World Health Organization (WHO) to assess eligibility for antiretroviral treatment (ART). (1,2) The CD4+ count also guides the clinical [...], Objective To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Medecins Sans Frontieres (MSF) in field projects and identify factors associated with invalid results. Methods We collated 25 616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; If not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with Invalid results. Findings There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere Pima[TM] devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3-19.9) and 12.1% (IQR: 7.1-19.2), respectively. The proportion of Invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood. Conclusion The Alere Pima CD4+ analyser generated a high proportion of Invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+T-lymphocyte testing. Objectif Estimer la proportion de resultats non valides generes par l&apos;analyseur de lymphocytes T CD4+ utilise par Medecins Sans Frontieres (MSF) dans les projets de terrain et determiner les facteurs associes aux resultats non valides. Methodes Nous avons rassemble 25 615 resultats de tests des lymphocytes T CD4+ realises sur 39 sites dans neuf pays entre 2011 et 2013. Un questionnaire a permis d&apos;obtenir des informations sur le lieu, l&apos;utilisateur, laformation, la methode d&apos;echantillonnageet les reparations effectuees sur l&apos;appareil. L&apos;analyseur realise une serie de controles afin de garantir que toutes les etapes de l&apos;analyse se deroulent correctement; si ce n&apos;est pas le cas, il Indique un resultat non valide. Nous avons calcule la proportion de resultats non valides par appareil et par operateur. Des analyses de regression ont permis de rechercher les facteurs associes aux resultats non valides. Resultats Nous avons releve 3354 resultats de tests non valides (13,1%) sur les 39 sites, avec 58 appareils Alere Pima[TM] et 180 operateurs. La proportion moyenne d&apos;erreurs par appareil et par operateur etait respectivement de 12,7% (intervalle interquartile, IQR: 10,3-19,9) et de 12,1% (IQR: 7,1-19,2). La proportion de resultats non valides variait conslderablement en fonction du pays, du lieu, de l&apos;utilisateur et de l&apos;appareil. Les erreurs n&apos;etaient pas associees aux lleux, a l&apos;experience de l&apos;utilisateur ou au nombre d&apos;utilisateurs par appareil. Les tests effectues sur des prelevements de sang capillaire etaient nettement moins susceptibles de generer des erreurs que ceux realises sur du sang veineux total. Conclusion L&apos;analyseur de CD4+ Alere Pima a genere une proportion elevee de resultats de tests non valides, dans differents pays, differents lieux et avec differents utilisateurs. La plupart des codes d&apos;erreur ont pu etre imputes a l&apos;operateur, mais les causes exactes se sont averees difficiles a determiner. Les resultats non valides doivent etre pris en compte dans les couts de mise en oeuvre et d&apos;exploitation des tests de routine des lymphocytes T CD4+. Objetivo Estimar la proporcion de resultados no validos generados por un analizador de linfocitos CD4+ T utilizado por Medicos sin Fronteras (MSF) en proyectos de campo e identificar los factores asociados a los resultados no validos. Metodos Se recopilaron 25 616 resultados de pruebas de linfocitos CD4+ T de 39 localizaciones en nueve paises entre los anos 2011 y 2013. Fa informacion sobre el entorno, los usuarios, la formacion, la tecnica de muestreo y el historial de reparacion del dispositivo se obtuvo a traves de un cuestionario. El analizador lleva a cabo una serie de chequeos para asegurar que se completan con exito todos los pasos del analisis; si no es asi, se informa de un resultado no valido. Se calculo la proporcion de resultados no validos por dispositivo y operador. Se utilizaron analisis de regresion para investigar los factores asociados con los resultados no validos. Resultados Hubo 3354 resultados no validos de pruebas (13,1%) en 39 localizaciones, para 58 dispositivos Alere Pima(tm) y 180 operadores. La proporcion media de errores por dispositivo y operador fue del 12,7% (rango intercuartilico, RIC: 10,3-19,9) y del 12,1% (RIC: 7,1-19,2), respectivamente. La proporcion de resultados no validos vario ampliamente entre paises, entornos, usuarios y dispositivos. Los errores no estaban asociados con los entornos, la experiencia del usuario o el numero de usuarios por dispositivo. Las pruebas realizadas con muestras de sangre capilar tenian menos posibilidades de generar error que las realizadas con sangre entera venosa. Conclusion El analizador Alere Pima CD4+ genero una alta proporcion de resultados no validos de pruebas en diferentes paises, entornos y usuarios. La mayoria de los codigos de error podrian atribuirse al operador, pero resulto dificil identificar las causas exactas. Los resultados no validos de las pruebas rutinarias de linfocitos CD4+ T deberian tenerse en cuenta en la aplicacion y los costes operacionales.