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Background: Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment. Methods: HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment. Results: Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm. Conclusions: In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART. [ABSTRACT FROM AUTHOR]

Background: In endemic regions, asymptomatic Leishmania infection is common. In HIV patients, detection of asymptomatic Leishmania infection could potentially identify those at risk of visceral leishmaniasis (VL). However, data on the prevalence, incidence, and determinants of asymptomatic infection, and the risk of VL are lacking. Methods: We conducted a cross-sectional survey at a single ART centre, followed by a prospective cohort study amongst HIV-infected adults in HIV care in a district hospital in a VL-endemic area in North-West Ethiopia (9/2015-8/2016). Asymptomatic Leishmania infection was detected using the direct agglutination test (DAT), rK39-rapid diagnostic test (RDT)), PCR on peripheral blood and the KAtex urine antigen test, and defined as positivity on any Leishmania marker. All individuals were followed longitudinally (irrespective of the Leishmania test results). Risk factors for asymptomatic Leishmania infection were determined using logistic regression. Results: A total of 534 HIV-infected individuals enrolled in HIV care were included in the study. After excluding 13 patients with a history of VL and an 10 patients with incomplete baseline Leishmania tests, 511 were included in analysis. The median age was 38 years (interquartile range (IQR) 30–45), 62.6% were male. The median follow-up time was 12 months (IQR 9–12). No deaths were reported during the study period. Most (95.5%) were on antiretroviral treatment at enrolment, for a median of 52 months (IQR 27–79). The median CD4 count at enrolment was 377 cells/mm3 (IQR 250–518). The baseline prevalence of Leishmania infection was 12.8% in males and 4.2% in females. Overall, 7.4% tested positive for rK39, 4.3% for DAT, 0.2% for PCR and 0.2% for KAtex. Independent risk factors for a prevalent infection were male sex (odds ratio (OR) 3.2; 95% confidence intervals (CI) 14–7.0) and concurrent malaria infection (OR 6.1; 95% CI 1.9–18.9). Amongst the 49 prevalent (baseline) infections with further follow-up, the cumulative incidence of losing the Leishmania markers by one year was 40.1%. There were 36 incident infections during the course of the study, with a cumulative one-year risk of 9.5%. Only one case of VL was detected during follow-up. Conclusions: We found a high prevalence of asymptomatic Leishmania infection, persisting in most cases. The incidence was more modest and overt VL was rare. Larger and longer studies with more complete follow-up may help to decide whether a test and treat strategy would be justified in this context. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: In Sub-Saharan Africa, both HIV/AIDS and anemia have considerable public health problems. Anemia has an adverse effect on treatment outcome and it decreases the quality of life among adult HIV patients. This study was aimed to assess the prevalence of anemia and its associated factors among adult HIV positive patients in Wolaita Sodo University Teaching Referral Hospital. Method: Institution based cross-sectional study was conducted at Wolaita Sodo University Teaching Referral Hospital from 01 October to December 30, 2016. A randomly selected 411 adult people living with the human immunodeficiency virus were included in the study. A pre-tested questionnaire was used to collect data. Variables with P-value ≤0.25 in the bivariable logistic regression model were taken into multivariable logistic regression analysis along with 95% confidence interval and Odds Ratio was used to examine the association between anemia and independent variables. P˗value ≤ 0.05 was taken as statistically significant. Result: Prevalence of anemia in this study was 36.5% with 95% CI (32%-41%). Factors associated with anemia among adult people living with HIV/AIDS were individuals who lived with HIV ≥9years (AOR = 2.6, 95% CI:-1.03–6.59),years lived with HIV 5–8 years (AOR = 2.59, 95% CI:-1.02–6.57),CD4 count <200cells/ul (AOR = 4.2, 95%CI:-2.03–8.67), CD4 count200-350cells/ul(AOR = 1.82,95%CI:-1.01–3.26),infection with intestinal parasites (AOR = 2.04, 95% CI:-1.06–3.95), Participants with BMI <18.5kg/m2 (AOR = 2.96, 95%CI:-1.37–6.390),BMI 18.5-25kg/m2(AOR = 1.98, 95%CI:-1.11–3.56) and being HAART naïve (AOR = 2.23, 95% CI:- 1.16–4.28). Conclusion: Prevalence of anemia among this study participant was high. This may affect the treatment outcome, increases morbidity and mortality of the participants. So periodic screening of anemia, a routine checkup of nutritional status, CD4 count and examination for intestinal parasite are essential. [ABSTRACT FROM AUTHOR]

Background: Since 2004, the President’s Emergency Plan for AIDS Relief (PEPFAR) has played a large role in Uganda’s HIV/AIDS response. To better target resources to high burden regions and facilities, PEPFAR planned to withdraw from 29% of previously-supported health facilities in Uganda between 2015 and 2017. Methods: We conducted a cross-sectional survey of 226 PEPFAR-supported health facilities in Uganda in mid-2017. The survey gathered information on availability, perceived quality, and access to HIV services before and after transition. We compare responses for facilities transitioned to those maintained on PEPFAR, accounting for survey design. We also extracted data from DHIS2 for the period October 2013–December 2017 on the number of HIV tests and counseling (HTC), number of patients on antiretroviral therapy (Current on ART), and retention on first-line ART (Retention) at 12 months. Using mixed effect models, we compare trends in service volume around the transition period. Results: There were 206 facilities that reported transition and 20 that reported maintenance on PEPFAR. Some facilities reporting transition may have been in a gap between implementing partners. The median transition date was September 2016, nine months prior to the survey. Transition facilities were more likely to discontinue HIV outreach following transition (51.6% vs. 1.4%, p<0.001) and to report declines in HIV care access (43.5% vs. 3.1%, p<0.001) and quality (35.6% vs. 0%, p<0.001). However, transition facilities did not differ in their trends in HIV service volume relative to maintenance facilities. Conclusions: Transition from PEPFAR resulted in facilities reporting worsening patient access and service quality for HIV care, but there is insufficient evidence to suggest negative impacts on volume of HIV services. Facility respondents’ perceptions about access and quality may be overly pessimistic, or they may signal forthcoming impacts. Unrelated to transition, declining retention on ART in Uganda is a cause for concern. [ABSTRACT FROM AUTHOR]

Nigeria has a plural legal system in which various sources of law govern simultaneously. Inconsistent and conflicting legal frameworks can reinforce pre–existing health disparities in sexual and reproductive health (SRH). While previous studies indicate poor SRH outcomes for Nigerian women and girls, particularly in Northern states, the relationship between customary and religious law (CRL) and SRH has not been explored. We conducted a state-level ecological study to examine the relationship between CRL and SRH outcomes among women in 36 Nigerian states and the Federal Capital Territory of Abuja (n = 37), using publicly available Demographic and Health Survey data from 2013. Indicators were guided by published research and included contraception use among married women, total fertility rate, median age at first birth, receipt of antenatal care, delivery location, and comprehensive knowledge of HIV. To account for economic differences between states, crude linear regression models were compared to a multivariable model, adjusting for per capita GDP. All SRH outcomes, except comprehensive knowledge of HIV, were statistically significantly more negative in CRL states compared to non–CRL states, even after accounting for state–level GDP. In CRL states in 2013, compared to non–CRL states, the proportion of married women who used any method of contraception was 22.7 percentage points lower ([95% CI: −15.78 –−29.64], p<0.001), a difference that persisted in a model adjusting for per capita GDP (b[adj] = −16.15, 95% CI: [−8.64 –−23.66], p<0.001.). While this analysis of retrospective state-level data found robust associations between CRL and poor SRH outcomes, future research should incorporate prospective individual-level data to further elucidate these findings. [ABSTRACT FROM AUTHOR]

Objective: Adoption of pre-exposure prophylaxis (PrEP) to prevent HIV infection has been slow. The purpose of this study was to evaluate knowledge, attitudes and referral practices for PrEP among non-prescribing providers, who may play key role. Methods: We performed a cross-sectional survey on PrEP knowledge, attitudes, and referral practices among 66 non-prescribing HIV prevention providers (1st August to 31st December, 2016), in Philadelphia, followed by qualitative interviews with 12 of them (5th April to 10th May, 2017). Results: Participants had a mean age of 36 years, with 62% females. Majority were HIV case managers and rapid testers. For half of the respondents, PrEP eligibility screening was part of rapid HIV testing at their organization, 40% never had PrEP training and only 27% indicated personally screening clients for eligibility. Qualitative data revealed that participants held positive attitudes about PrEP and perceived organizational support, but had concerns about potential negative impacts and barriers to routine HIV screening. Conclusion: Results highlight the importance of training non-prescribing HIV prevention providers about PrEP, addressing their concerns, and incorporating PrEP screening and referral into routine HIV testing. [ABSTRACT FROM AUTHOR]

Background: Little has been documented about partner violence among adolescent girls and young women (AGYW) who are out of school, a factor associated with HIV acquisition. To understand areas for prioritising HIV prevention intervention efforts, we explored the prevalence and correlates of partner violence among out of school AGYW in Shinyanga, Tanzania. Methods: A cross-sectional analysis of data from AGYW aged 15–23 years recruited in a cluster randomised trial conducted between October and December 2017 was used to examine correlates of partner violence. Data were collected through an Audio Computer-Assisted Self-interview. Multivariate logistic regression analysis was used to evaluate the association. Results: 2276 (75.5%) AGYW were sexually active. Of these, 816 (35.9%) reported having experienced violence from partners in the last six months. After adjusting for other covariates, being formerly married (AOR = 1.55, 95% CI:1.02, 2.37), having children (AOR = 1.79, 95% CI:1.47, 2.16), anxiety and depression symptoms (AOR = 3.27, 95%CI: 2.15, 4.96), having engaged in sex work in the past six months (AOR = 1.92, 95% CI: 1.45, 2.53) and economic deprivation (AOR = 1.61, 95% CI: 1.34,1.92) were significantly associated with partner violence. Conclusions: Almost one in three sexually active AGYW had experienced partner violence in the 6 months preceding the survey. The findings underscore the need for future research to focus on understanding the reasons and dynamics underlying high level of partner violence among AGYW. Furthermore, there is a need for implementing intervention programs that aim to reduce economic deprivation among AGYWs and address social norms and structures perpetuating violence against AGYW. Trial registration: ClinicalTrials.gov—ID . [ABSTRACT FROM AUTHOR]

Background: India has recently introduced telemedicine initiatives to enhance access to specialized care at a low cost for the pediatric HIV patients, who face multiple challenges due to growing disease burden and limited preparedness of the health system to address it. There are limited evidences on the cost-effectiveness of these interventions. This study was undertaken in Maharashtra, a province, located in the western region of the country, to inform policy regarding the effectiveness of this programme. The objective was to estimate the unit cost of ART services for pediatric HIV patients and examine the efficiency in the use of resource and treatment compliance resulting from telemedicine initiatives in pediatric HIV compared to usual ART services. Methods: We selected 6 ART centers (3 from linked centers linked to Pediatric HIV Centre of Excellence (PCoE) and 3 from non-linked centers) randomly from three high, middle and low ART centers, categorized on the basis of case load in each arm. A bottom up costing methodology was adopted to understand the unit cost of services. Loss to follow up and timeliness of the visits were compared between the two arms and were linked to the cost. Results: The average cost per-visit was INR 1803 in the linked centers and that for the non-linked centers was INR 3412. There has been 5 percentage point improvement in lost to follow-up in the linked centers compared to non-linked centers against a back-drop of a reduction in per-pediatric patient cost of INR 557. The linkage has resulted in increase in timeliness of the visits in linked centers compared to non-linked centers. Discussion and conclusion: The telemedicine linkage led to an increase in the case load leading to a decrease in cost. The evidence on efficiency in the use of resource and improvement in treatment compliance as suggested by this study could be used to scale up this initiative. [ABSTRACT FROM AUTHOR]

High HIV incidence rates have been observed among pregnant and breastfeeding women in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) can effectively reduce HIV acquisition in women during these periods; however, understanding of its acceptability and feasibility in antenatal and postpartum populations remains limited. To address this gap, we conducted in-depth interviews with 90 study participants in Malawi and Zambia: 39 HIV-negative pregnant/breastfeeding women, 14 male partners, 19 healthcare workers, and 18 policymakers. Inductive and deductive approaches were used to identify themes related to PrEP. As a public health intervention, PrEP was not well-known among patients and healthcare workers; however, when it was described to participants, most expressed positive views. Concerns about safety and adherence were raised, highlighting two critical areas for community outreach. The feasibility of introducing PrEP into antenatal services was also a concern, especially if introduced within already strained health systems. Support for PrEP varied among policymakers in Malawi and Zambia, reflecting the ongoing policy discussions in their respective countries. Implementing PrEP during the pregnancy and breastfeeding periods will require addressing barriers at the individual, facility, and policy levels. Multi- level approaches should be considered in the design of new PrEP programs for antenatal and postpartum populations. [ABSTRACT FROM AUTHOR]

HIV-1 gene expression is regulated by host and viral factors that interact with viral motifs and is influenced by proviral integration sites. Here, expression variation among integrants was followed for hundreds of individual proviral clones within polyclonal populations throughout successive rounds of virus and cultured cell replication, with limited findings using CD4+ cells from donor blood consistent with observations in immortalized cells. Tracking clonal behavior by proviral “zip codes” indicated that mutational inactivation during reverse transcription was rare, while clonal expansion and proviral expression states varied widely. By sorting for provirus expression using a GFP reporter in the nef open reading frame, distinct clone-specific variation in on/off proportions were observed that spanned three orders of magnitude. Tracking GFP phenotypes over time revealed that as cells divided, their progeny alternated between HIV transcriptional activity and non-activity. Despite these phenotypic oscillations, the overall GFP+ population within each clone was remarkably stable, with clones maintaining clone-specific equilibrium mixtures of GFP+ and GFP- cells. Integration sites were analyzed for correlations between genomic features and the epigenetic phenomena described here. Integrants inserted in the sense orientation of genes were more frequently found to be GFP negative than those in the antisense orientation, and clones with high GFP+ proportions were more distal to repressive H3K9me3 peaks than low GFP+ clones. Clones with low frequencies of GFP positivity appeared to expand more rapidly than clones for which most cells were GFP+, even though the tested proviruses were Vpr-. Thus, much of the increase in the GFP- population in these polyclonal pools over time reflected differential clonal expansion. Together, these results underscore the temporal and quantitative variability in HIV-1 gene expression among proviral clones that are conferred in the absence of metabolic or cell-type dependent variability, and shed light on cell-intrinsic layers of regulation that affect HIV-1 population dynamics. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the HIV/syphilis epidemic among men who have sex with men (MSM) aged <50 years and ≥50 years in Shenzhen, and explore the associated factors of HIV/syphilis co-infections among MSM in Shenzhen, in order to help prevention and intervention programs determine their target sub-group. A serial cross-sectional study was conducted on MSM in Shenzhen city, China from 2009 to 2017. A questionnaire was used to collect demographic characteristics, history of HIV testing, history of blood donation and sexual behaviors. 5 ml of venous blood were collected for syphilis and HIV tests. The overall prevalence of HIV, syphilis, HIV/syphilis co-infection was 9.40%, 18.97%, and 4.91%, respectively. The prevalence of HIV (15.26%), syphilis (27.71%), HIV/syphilis co-infection (9.24%) in aged ≥50 years MSM was significantly higher than aged <50 years MSM (9.15%, 18.59% and 4.72%, respectively). The following factors were found to be significantly associated with HIV/syphilis co-infections (P<0.05): age≥50 years (OR = 1.78, 95% CI = 1.10–2.87), high school or lower (OR = 1.49, 95% CI = 1.10–2.01), monthly income ≤436.2 USD (OR = 1.74, 95% CI = 1.25–2.42), monthly income 436.4–727.2 USD (OR = 1.46, 95% CI = 1.05–2.03), ≥2 anal sex partners in the past 6 months (OR = 1.59, 95% CI = 1.02–2.49), ≥2 oral sex partners in the past 6 months (OR = 1.60, 95% CI = 1.08–2.36), inconsistent condom use during anal sex in the past 6 months (OR = 1.50, 95% CI = 1.11–2.03). We found that aged <50 years and ≥50 years MSM in Shenzhen had a high prevalence of HIV/syphilis infection in a period from 2009 to 2017. Age-specific sexually transmitted diseases education, prevention, and intervention programs for aged ≥50 years MSM should be implemented urgently and integrated interventions of both HIV and syphilis infections on MSM are needed in the future. [ABSTRACT FROM AUTHOR]

Introduction: Given constrained funding for Human Immunodeficiency Virus (HIV) programs across Sub-Saharan Africa, delivering services efficiently is paramount. Voluntary medical male circumcision (VMMC) is a key intervention that can substantially reduce heterosexual transmission—the primary mode of transmission across the continent. There is limited research, however, on what factors may contribute to the efficient and high-quality execution of such programs. Methods: We analyzed a multi-country, multi-stage random sample of 108 health facilities providing VMMC services in sub-Saharan Africa in 2012 and 2013. The survey collected information on inputs, outputs, process quality and management practices from facilities providing VMMC services. We analyzed the relationship between management practices, quality (measured through provider vignettes) and efficiency (estimated through data envelopment analysis) using Generalized Linear Models and Mixed-effects Models. Applying multivariate regression models, we assessed the relationship between management indices and efficiency and quality of VMMC services. Results: Across countries, both efficiency and quality varied widely. After adjusting for type of facility, country and scale, performance-base funding was negatively correlated with efficiency -0.156 (p < 0.05). In our analysis, we did not find any significant relationships between quality and management practices. Conclusions: No significant relationship was found between process quality and management practices across 108 VMMC facilities. This study is the first to analyze the potential relationships between management and service quality and efficiency among a sample of VMMC health facilities in sub-Saharan Africa and can potentially inform policy-relevant hypotheses to later test through prospective experimental studies. [ABSTRACT FROM AUTHOR]

Setting: Four primary health care clinics providing tuberculosis (TB) and Human Immunodeficiency Virus care services in Bulawayo, Zimbabwe. Objectives: To assess isoniazid preventive therapy (IPT) initiation and completion, factors associated with IPT uptake and incidence of TB, and TB and antiretroviral treatment (ART) outcomes among people living with HIV (PLHIV). Design: This was a cohort study using routine data in the records for PLHIV initiated on ART from October 2013 to March 2014 with 31 December 2017 as the end of the follow-up period. Results: A total of 408 PLHIV were eligible for IPT, 214 (52%) were initiated on IPT and 201 (94%) completed IPT. No person in the IPT-initiated group developed Tuberculosis (TB). Six persons with TB were reported among the non-IPT-initiated group leading to an incidence of 9 cases/1,000 person-years of follow-up. About 70% of those who developed and were treated for TB had a successful TB treatment outcome. The survival on ART at four years of follow-up was 88% among the IPT-initiated PLHIV that was significantly higher than the 75% survival in the group not- initiated on IPT. Conclusion: The study revealed low IPT initiation among eligible PLHIV who, if started on IPT, completed the six month regimen. TB was reported only among the PLHIV not-initiated on IPT and the four year ART survival was higher in the IPT-initiated group than in the non-initiated group. These findings reinforce the need to strengthen IPT uptake among PLHIV in Bulawayo. [ABSTRACT FROM AUTHOR]

Background: Timely diagnosis of infant HIV infection is essential for antiretroviral therapy (ART) initiation. In a randomized controlled trial, we found the Texting Improves Testing (TextIT) intervention (a theory-based text messaging system) to be efficacious for improving infant HIV testing rates and maternal retention in prevention of mother-to-child HIV transmission (PMTCT) programs. Using an implementation science approach, we aimed to evaluate real-world effectiveness of the intervention.Methods and Findings: In a pragmatic, cluster-randomized, stepped-wedge trial with 2 time periods of observation, we randomly allocated 10 clinics to begin implementing the intervention immediately and 10 clinics to begin implementing 6 months later. To approximate real-world conditions, inclusion criteria were broad. Women at clinics implementing the intervention received up to 14 text messages during pregnancy and after delivery and had the option to respond to text messages, call, or send inquiry text messages to a designated clinic phone. The primary outcomes were infant HIV testing and maternal retention in care during the first 8 weeks after delivery. We used modified Poisson regression with robust variance estimation to estimate the relative risk and 95% confidence intervals (CIs). Generalized estimating equations were applied on individual-level data to account for clustering by site. Between February 2015 and December 2016, 4,681 women were assessed for study participation, and 2,515 were included. Participant characteristics at enrollment did not differ by study arm. Overall median age was 27 years (interquartile range [IQR] 23-30), median gestational age was 30 weeks (IQR 28-34), 99% were receiving ART, and 87% who enrolled during intervention phases owned a phone. Of 2,326 infants analyzed, 1,466 of 1,613 (90.9%) in the intervention group and 609 of 713 (85.4%) in the control group met the primary outcome of HIV virologic testing performed before 8 weeks after birth (adjusted relative risk [aRR] 1.03; 95% CI 0.97-1.10; P = 0.3). Of 2,472 women analyzed, 1,548 of 1,725 (90%) in the intervention group and 571 of 747 (76%) in the control group met the primary outcome of retention in care during the first 8 weeks after delivery (aRR 1.12; 95% CI 0.97-1.30; P = 0.1). This study had two main limitations. Staff at all facilities were aware of ongoing observation, which may have contributed to increased rates of infant HIV testing and maternal retention in care at both intervention and control facilities, and programmatic initiatives to improve maternal and infant retention in care were ongoing at all facilities at the time of this study, which likely limited the ability to demonstrate effectiveness of the trial intervention.Conclusions: In this study, a larger proportion of infants in the intervention group received HIV testing compared with the control group, but the difference was small and not statistically significant. There was also a nonsignificant increase in maternal postpartum retention in the intervention periods. Despite the lack of a significant effect of the intervention, key lessons emerged, both for strengthening PMTCT and for implementation research in general. Perhaps most important, improving the implementation of usual care may have been sufficient to substantially improve infant HIV testing rates.Trial Registration: ClinicalTrials.gov Trial Number NCT02350140. [ABSTRACT FROM AUTHOR]

Background: COPD is a common HIV comorbidity, and HIV-infected individuals have a higher incidence and earlier onset of COPD compared to HIV-uninfected individuals. While the pathogenesis of HIV-associated COPD is largely unknown, chronic inflammation may contribute. Four pneumoproteins known to be markers of lung injury and inflammation have been associated with COPD in HIV-uninfected individuals: PARC/CCL-18, SP-D, CC-16, and sRAGE. Objective: To determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals. Methods: Associations between plasma pneumoprotein levels and pulmonary function were determined in a cross-sectional study of otherwise healthy HIV-infected individuals enrolled between September 2016 and June 2017. Covariates included HIV-associated (antiretroviral therapy, CD4 count, and viral load) and COPD-associated (smoking and BMI) covariates. Results: Among 65 participants, 78.5% were male, 50.8% had undetectable viral load, and 76.9% were ever-smokers. Mean post-bronchodilator FEV1/FVC was 0.71, and mean DLco%predicted was 61%. Higher PARC/CCL-18 was associated with lower DLco%predicted and higher CAT score. Higher CC-16 was associated with lower DLco%predicted and lower FVC%predicted. Conclusions: This exploratory analysis is the first to characterize associations between these four pneumoproteins and pulmonary function in an HIV-infected cohort. Our findings suggest the pathogenesis of HIV-associated COPD may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco. PARC/CCL-18 is associated with structural and functional pulmonary abnormalities and may be an important COPD biomarker candidate in HIV infection. Our study is a preliminary step toward finding clinically relevant COPD biomarkers in high-risk populations. [ABSTRACT FROM AUTHOR]

Background: Guyana expanded its HIV response in 2005 but the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has not been characterized. Methods: The 2011 Seroprevalence and Behavioral Epidemiology Risk Survey for HIV and STIs collected biologic specimens with demographic and behavioral data from a representative sample of Guyana military personnel. Diagnostics included commercial serum: HIV antibody; total antibody to hepatitis B core (anti-HBc); IgM anti-HBc; hepatitis B surface antigen (HBsAg); anti-HBs; antibody to HCV with confirmatory testing; and HBV DNA sequencing with S gene fragment phylogenetic analysis. Chi-square, p-values and prevalence ratios determined statistical significance. Results: Among 480 participants providing serologic specimens, 176 (36.7%) tested anti-HBc-positive. Overall, 19 (4.0%) participants tested HBsAg-positive; 17 (89.5%) of the HBsAg-positive participants also had detectable anti-HBc, including 1 (5.3%) IgM anti-HBc-positive male. Four (6.8%) females with available HBV testing were HBsAg-positive, all aged 23–29 years. Sixteen (16, 84.2%) HBsAg-positive participants had sufficient specimen for DNA testing. All 16 had detectable HBV DNA, 4 with viral load >2x104IU/ml. Sequencing found: 12 genotype (gt) A1 with 99.9% genetic identity between 1 IgM anti-HBc-positive and 1 anti-HBc-negative; 2 gtD1; and 2 with insufficient specimen. No statistically significant associations between risk factors and HBV infection were identified. Conclusions: Integrated HIV surveillance identified likely recent adult HBV transmission, current HBV infection among females of reproductive age, moderate HBV infection prevalence (all gtA1 and D1), no HCV infections and low HIV frequency among Guyana military personnel. Integrated HIV surveillance helped characterize HBV and HCV epidemiology, including probable recent transmission, prompting targeted responses to control ongoing HBV transmission and examination of hepatitis B vaccine policies. [ABSTRACT FROM AUTHOR]

Introduction: Data on engagement in HIV care from population-based samples in sub-Saharan Africa are limited. The objective of this study was to use double-sampling methods to estimate linkage to HIV care, ART initiation, and mortality among all adults diagnosed with HIV by a comprehensive home-based counseling and testing (HBCT) program in western Kenya. Methods: HBCT was conducted door-to-door from December 2009 to April 2011 in three sub-counties of western Kenya by AMPATH (Academic Model Providing Access to Healthcare). For those identified as HIV-positive, data were merged with electronic medical records to determine engagement with HIV care. A randomly-drawn follow-up sample of 120 adults identified via HBCT who had not linked to care as of June 2015 in Bunyala sub-county were visited by trained fieldworkers to ascertain HIV care engagement and vital status. Double-sampled data were used to generate, via multinomial regression, predicted probabilities of engagement in care and mortality among those whose status could not be ascertained by matching with the electronic medical records in the three catchments. Results: Incorporating information from the double-sampling yielded estimates of prospective linkage to HIV care that ranged from 40–45%. Mortality estimates of those who did not engage in care following HBCT ranged from 12–16%. Among those who linked to care following HBCT, between 72–81% initiated ART. Discussion: In settings without universal national identifiers, rates of linkage to care from community-based programs may be subject to substantial underestimation. Follow-up samples of those with missing information can be used to partially correct this bias, as has been demonstrated previously for mortality among those who were lost-to-care programs. There is a need for harmonized data systems across health systems and programs. [ABSTRACT FROM AUTHOR]

Background: Protease inhibitors (PI) are especially important in salvage therapy. Previous treatment failure with a PI containing regimen may elicit resistance mutations, reducing PI susceptibility and limiting treatment options. The aim of this study was to describe major PI mutations among patients exposed to at least one PI to evaluate predictors of mutation emergence and the impact of subtypes on resistance. Methodology: Partial HIV-1 pol sequences (Sanger Sequencing) from patients exposed to PI with virological failure were genotyped from January 2014 to December 2017. Drug resistance mutations (DRM), antiretroviral susceptibility (GSS) and subtypes, along clinical and laboratory parameters, were evaluated using logistic regression to access the predictors of mutation emergence. Results: In 27.5% (466/1696) of the cases at least one major PI mutations was identified, most commonly M46 (14.7%), V82 (13.8%) and I54 (13.3%). Mutations to NRTI and NNRTI were observed in 69.6% and 59.9%, respectively, of the 1696 sequences. Full activity to darunavir was predicted in 88% (1496/1696), but was only 57% among those with at least one PI-DRM. Subtype C sequences had less major PI-DRMs (10%, 9/87) compared to B (28%, 338/1216) or F (35%, 58/168) (p <0.001) but adjusted analysis suggested that this association is not independent from a shorter treatment time and fewer regimens (OR 0.59, Confidence Interval 95: 0.2–2.5, p = 0.48). Subtype F, together with NRTI mutations and longer time on treatment was associated to presence of PI-DRM, to a lower darunavir GSS and to mutations at codon I50. Conclusions: Among patients with PI-DRM, full activity to darunavir was compromised in almost half of the cases and efforts to detect failure at earlier time are warranted, particularly for HIV-1 subtype F that showed association to the emergence of resistance, with potential impact in protease inhibitors sequencing. Furthermore, NRTI mutations may serve as an indicative of sufficient adherence to allow PI-DRM emergence. [ABSTRACT FROM AUTHOR]

Background: TB/HIV coinfection is a serious public health issue in Brazil, and patients with coinfection have difficulty adhering to treatments. Directly observed treatment (DOT) has been recommended by the World Health Organization, considering the vulnerability of those affected. The purpose is to investigate the occurrence of DOT and associated factors compared to conventional treatment in Porto Alegre, Brazil. Methods: A retrospective cohort study was carried out with all patients with coinfection from 2009 to 2013 in the city of Porto Alegre, Brazil, the state capital with the highest rate of coinfection in Brazil. The data came from national health information systems. The dependent variable was the performance of DOT. Bivariate and multivariable models were used to determine factors associated with DOT. The percentage of cure and death was verified in a period of two years, comparing patients who received and did not receive DOT. Results: 2,400 cases of coinfection were reported, with 1,574 males and 826 females and a mean age of 38 years ± 9.91 years. The occurrence of DOT was 16.9%. In the multivariable analysis, factors independently associated to DOT were the year (with greater chances of being received in 2012 and 2013), place of origin, non-white race (OR = 1.29, 95% CI = 1.08–1.54), cases of relapse (OR = 1.33; 95% CI = 1.03–1.73), readmission after abandonment (OR = 1.48, 95% CI = 1.20–1.83), transfer (OR = 2.04; 95% CI = 1.40–2.98), acid-fast bacilli (AFB) test with positive result in first sample (OR = 1.73, 95% CI = 1.24–2.42), alcohol abuse (OR = 1.39; 95% CI = 1.16–1.67), and mental disorders (OR = 1.83; 95% CI = 1.38–2.44.) Of the 532 cases of death, occurring in two years, 10.2% were in patients who underwent DOT and 89.8% in patients who did not undergo DOT (p<0.001). O percentual de óbitos em pessoas que receberam DOT foi de 13% e o percentual de óbitos para pessoas que receberam tratamento convencional foi de 24%. Conclusions: There was an increase in the percentage of DOT over the years in the scenario studied, and the predictors for DOT were related to social vulnerability. In relation to death within two years, a lower proportion was found in patients who underwent DOT, suggesting a protective effect of the strategy. [ABSTRACT FROM AUTHOR]

Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We characterized microbial communities in vaginal swabs collected between 16–20 gestational weeks in the Zambian Preterm Birth Prevention Study to investigate whether HIV and its treatment alter the microbiome in pregnancy. We quantified relative abundance and diversity of bacterial taxa by whole-genome shotgun sequencing and identified community state types (CST) by hierarchical clustering. Associations between exposures—HIV serostatus (HIV+ vs HIV-) and preconceptional ART (ART+ vs ART-)—and microbiome characteristics were tested with rank-sum, and by linear and logistic regression, accounting for sampling by inverse-probability weighting. Of 261 vaginal swabs, 256 (98%) had evaluable sequences; 98 (38%) were from HIV+ participants, 55 (56%) of whom had preconceptional ART exposure. Major CSTs were dominated by: L. crispatus (CST 1; 17%), L.] iners (CST 3; 32%), Gardnerella vaginalis (CST 4-I; 37%), G. vaginalis & Atopobium vaginae (CST 4-II; 5%), and other mixed anaerobes (CST 4-III; 9%). G. vaginalis was present in 95%; mean relative abundance was higher in HIV+ (0.46±0.29) compared to HIV- participants (0.35±0.33; rank-sum p = .01). Shannon diversity was higher in HIV+/ART+ (coeff 0.17; 95%CI (0.01,0.33), p = .04) and HIV+/ART- (coeff 0.37; 95%CI (0.19,0.55), p < .001) participants compared to HIV-. Anaerobe-dominant CSTs were more prevalent in HIV+/ART+ (63%, AOR 3.11; 95%CI: 1.48,6.55, p = .003) and HIV+/ART- (85%, AOR 7.59; 95%CI (2.80,20.6), p < .001) compared to HIV- (45%). Restricting the comparison to 111 women in either CST 3 (L. iners dominance) or CST 1 (L. crispatus dominance), CST 3 frequency was similar in HIV- (63%) and HIV+/ART- participants (67%, AOR 1.31; 95%CI: (0.25,6.90), p = .7), but higher in HIV+/ART+ (89%, AOR 6.44; 95%CI: (1.12,37.0), p = .04). Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota. [ABSTRACT FROM AUTHOR]

Background: Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines. Methods: Demographic, clinical and genomic data were collected from 3599 HIV-1 naive patients between 2001 and 2014. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses. Results: In Portugal, transmission of subtype B was significantly associated with young males, while transmission of subtype G was associated with older heterosexuals. In Portuguese originated people, there was a decreasing trend both for prevalence of subtype G and for number of TCs in this subtype. The active TCs that were identified (i.e. clusters originated after 2008) were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5–12.2]) and G (7.6% [6.4–9.0]) (p = 0.001). Discussion: TC analyses shows that, in Portugal, the subtype B epidemic is active and fueled by young male patients residing in Lisbon, while transmission of subtype G is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is significantly different between subtypes. [ABSTRACT FROM AUTHOR]

A prophylactic vaccine against human immunodeficiency virus (HIV) remains a top priority in biomedical research. Given the failure of conventional immunization protocols to confer robust protection against HIV, new and unconventional approaches may be needed to generate protective anti-HIV immunity. Here we vaccinated rhesus macaques (RMs) with a recombinant (r)DNA prime (without any exogenous adjuvant), followed by a booster with rhesus monkey rhadinovirus (RRV)−a herpesvirus that establishes persistent infection in RMs (Group 1). Both the rDNA and rRRV vectors encoded a near-full-length simian immunodeficiency virus (SIVnfl) genome that assembles noninfectious SIV particles and expresses all nine SIV gene products. This rDNA/rRRV-SIVnfl vaccine regimen induced persistent anti-Env antibodies and CD8+ T-cell responses against the entire SIV proteome. Vaccine efficacy was assessed by repeated, marginal-dose, intrarectal challenges with SIVmac239. Encouragingly, vaccinees in Group 1 acquired SIVmac239 infection at a significantly delayed rate compared to unvaccinated controls (Group 3). In an attempt to improve upon this outcome, a separate group of rDNA/rRRV-SIVnfl-vaccinated RMs (Group 2) was treated with a cytotoxic T-lymphocyte antigen-4 (CTLA-4)-blocking monoclonal antibody during the vaccine phase and then challenged in parallel with Groups 1 and 3. Surprisingly, Group 2 was not significantly protected against SIVmac239 infection. In sum, SIVnfl vaccination can protect RMs against rigorous mucosal challenges with SIVmac239, a feat that until now had only been accomplished by live-attenuated strains of SIV. Further work is needed to identify the minimal requirements for this protection and whether SIVnfl vaccine efficacy can be improved by means other than anti-CTLA-4 adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: The implementation of quality HIV control programs is crucial for the achievement of the UNAIDS 90-90-90 targets and to motivate people living with HIV (PLWHIV) to link and remain in HIV-care. The aim of this mixed method cross-sectional study was to estimate the linkage and long-term retention in care of PLWHIV and to identify factors potentially interfering along the HIV-care continuum in southern Mozambique. Methods: A home-based semi-structured interview was conducted in 2015 to explore barriers and facilitators to the HIV-care cascade among individuals that had been newly HIV-diagnosed in community testing campaigns in 2010 or 2012. Linkage and long-term retention were estimated retrospectively through client self-reports and clinical records. Cohen's Kappa coefficient was calculated to measure the agreement between participant self-reported and documented cascade outcomes. Results: Among the 112 interviewed participants, 24 (21.4%) did not disclose their HIV-positive serostatus to the interviewer. While 84 (75.0%) self-reported having enrolled in care, only 69 (61.6%) reported still being in-care 3–5 years after diagnosis of which 17.4% reported having disengaged and re-engaged. An important factor affecting optimal continuum in HIV-care was the impact of the fear-based authoritarian relationship between the health system and the patient that could act as both driver and barrier. Conclusion: Special attention should be given to quantify and understand repeated cycles of patient disengagement and re-engagement in HIV-care. Strategies to improve the relationship between the health system and patients are still needed in order to optimally engage PLWHIV for long-term periods. [ABSTRACT FROM AUTHOR]

Background: Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods: Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results: In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions: Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48. Trial registration: EUDRACT number: [ABSTRACT FROM AUTHOR]

Objective: This is the first large-scale assessment of the implementation of HIV Rapid Test Quality Improvement Initiative in South Africa. Methods: We used a quasi-experimental one group post-test only design. The intervention implemented starting April 2014 comprised health-care worker training on quality assurance (QA) of HIV rapid testing and enrolment of the facilities in proficiency testing (PT), targeting 2,077 healthcare facilities in 32 high HIV burden districts. Following the intervention, two consecutive rounds of site assessments were undertaken. The first, conducted after a median of 7.5 months following the training, included 1,915 facilities that participated in the QA training, while the second, conducted after a median of one-year following the first-round assessment included 517 (27.0%) of the 1,915 facilities. In both assessments, the Stepwise-Process-for-Improving-the-quality-of-HIV-Rapid-Testing (SPI-RT) checklist was used to score facilities’ performance in 7 domains: training, physical facility, safety, pre-testing, testing, post-testing and external quality assessment. Facilities’ level of readiness for national certification was assessed. Result: Between 2016 and 2017, there were four PT cycles. PT participation increased from 32.4% (620/1,915) in 2016 to 91.5% (1,753/1,915) in 2017. In each PT cycle, PT results were returned by 76%–87% of facilities and a satisfactory result (>80%) was achieved by ≥95% of facilities. In the SPI-RT assessment, in round-one, 22.3% of facilities were close to or eligible for national certification—this significantly increased to 38.8% in round-two (P-value<0.001). The median SPI-RT score for the domains HIV pre-testing (83.3%) and post-testing (72.2%) remained the same between the two rounds. The median score for the testing domain increased by 5.6% (to 77.8%). Conclusion: Facilities performance on the domains that are critical for accuracy of diagnosis (i.e. pre-testing, testing and post-testing) remained largely unchanged. This study provided several recommendations to improve QA implementation in South Africa, including the need to improve routine use of internal quality control for corrective actions. [ABSTRACT FROM AUTHOR]

Introduction: Since 2011, Kenya has been evaluating ShangRing device for use in its voluntary medical male circumcision (VMMC) program according to World Health Organization (WHO) guidelines. Compared to conventional surgical circumcision, the ShangRing procedure is shorter, does not require suturing and gives better cosmetic outcomes. After a pilot evaluation of ShangRing in 2011, Kenya conducted an active surveillance for adverse events associated with its use from 2016–2018 to further assess its safety, uptake and to identify any operational bottlenecks to its widespread use based on data from a larger pool of procedures in routine health care settings. Methods: From December 2017 to August 2018, HIV-negative VMMC clients aged 13 years or older seeking VMMC at six sites across five counties in Kenya were offered ShangRing under injectable local anesthetic as an alternative to conventional surgical circumcision. Providers described both procedures to clients before letting them make a choice. Outcome measures recorded for clients who chose ShangRing included the proportions who were clinically eligible, had successful device placement, experienced adverse events (AEs), or failed to return for device removal. Clients failing to return for follow up were sought through phone calls, text messages or home visits to ensure removal and complete information on adverse events. Results: Out of 3,692 eligible clients 1,079 (29.2%) chose ShangRing; of these, 11 (1.0%) were excluded due to ongoing clinical conditions, 17 (1.6%) underwent conventional surgery due to lack of appropriate device size at the time of the procedure, 97.3% (1051/1079) had ShangRing placement. Uptake of ShangRing varied from 11% to 97% across different sites. There was one severe AE, a failed ShangRing placement (0.1%) managed by conventional wound suturing, plus two moderate AEs (0.2%), post removal wound dehiscence and bleeding, that resolved without sequelae. The overall AE rate was 0.3%. All clients returned for device removal from fifth to eleventh day after placement. Conclusion: ShangRing circumcision is effective and safe in the Kenyan context but its uptake varies widely in different settings. It should be rolled out under programmatic implementation for eligible males to take advantage of its unique benefits and the freedom of choice beyond conventional surgical MMC. Public education on its availability and unique advantages is necessary to optimize its uptake and to actualize the benefit of its inclusion in VMMC programs. [ABSTRACT FROM AUTHOR]

The transition to PEPFAR 2.0 with its focus on country ownership was accompanied by substantial funding cuts. We describe the impact of this transition on HIV care in a large network of HIV clinics in Nigeria. We surveyed 30 comprehensive HIV treatment clinics to assess services supported before (October 2013-September 2014) and after (October 2014-September 2015) the PEPFAR funding policy change, the impact of these policy changes on service delivery areas, and response of clinics to the change. We compared differences in support for staffing, laboratory services, and clinical operations pre- and post-policy change using paired t-tests. We used framework analysis to assess answers to open ended questions describing responses to the policy change. Most sites (83%, n = 25) completed the survey. The majority were public (60%, n = 15) and secondary (68%, n = 17) facilities. Clinics had a median of 989 patients in care (IQR: 543–3326). All clinics continued to receive support for first and second line antiretrovirals and CD4 testing after the policy change, while no clinics received support for other routine drug monitoring labs. We found statistically significant reductions in support for viral load testing, staff employment, defaulter tracking, and prevention services (92% vs. 64%, p = 0.02; 80% vs. 20%, 100% vs. 44%, 84% vs. 16%, respectively, p<0.01 for all) after the policy change. Service delivery was hampered by interrupted laboratory services and reduced wages and staff positions leading to reduced provider morale, and compromised quality of care. Almost all sites (96%) introduced user fees to address funding shortages. Clinics in Nigeria are experiencing major challenges in providing routine HIV services as a result of PEPFAR’s policy changes. Funding cutbacks have been associated with compromised quality of care, staff shortages, and reliance on fee-based care for historically free services. Sustainable HIV services funding models are urgently needed. [ABSTRACT FROM AUTHOR]

Introduction: Measures used to assess equitable relationship dynamics, including the sexual relationship power scale (SRPS) have previously been associated with lower HIV-risk among young women, and reduced perpetration of intimate partner violence among men. However, few studies describe how the SRPS has been adapted and validated for use within global youth sexual health studies. We examined gender-specific psychometric properties, reliability, and validity of a SRPS used within a South African youth-engaged cohort study. Methods: Young men and women (16–24 years) enrolled in community-based cohorts in Durban and Soweto (2014–2016) reporting a primary partner at 6-month follow-up completed a 13-item (strongly agree/agree/disagree/strongly disagree) South African adaptation of Pulerwitz’s SRPS (range 13–52, higher scores indicating greater sexual relationship power [SRP] equity). SRPS modifications were made using gender-specific exploratory factor analyses (EFAs), removing items with factor loadings <0.3. Cronbach alphas were conducted for full and modified scales by gender. Using modified scales, unadjusted and adjusted regression models examined associations between 1. relevant socio-demographic and relationship determinants and SRP equity, and 2. SRP equity and sexual relationship related outcomes. All models adjusted for education, age, site, and current employment. Results: 235 sexually-active youth (66% women, median age = 20) were included. Mean scores across all 13 scale items were 2.71 (SD 0.30) for women and 2.70 (SD 0.4) for men. Scale Cronbach’s alphas were 0.63 for women and 0.64 for men. EFAs resulted in two gender-specific single-factor SRPS. Modified SRPS Cronbach alphas increased to 0.67 for women (8-items) and 0.70 for men (9-items). After adjusting for age, site and current employment, higher education remained associated with SRP equity across genders. In adjusted models, correlates of SRP equity included primary partnerships that were age-similar (<5 years older) and <2 years in length for women and living in Soweto and younger age for men. Greater SRP equity among women was also independently associated with no recent partner violence. Conclusions: Results highlight important gender differences in SRP equity measures and associations, highlighting the critically need for future research to examine gendered constructions of SRP equity in order to accurately develop, validate and use appropriate measures within quantitative surveys. [ABSTRACT FROM AUTHOR]

Context: High rates of burnout have been reported in low and medium income countries and can detrimentally impact healthcare delivery. Understanding factors associated with burnout amongst health care workers providing HIV care may help develop interventions to prevent/treat burnout. Objectives: We sought to understand factors associated with burnout amongst health care workers providing HIV care in Malawi. Methods: This was a sub-study of a larger cross-sectional study measuring burnout prevalence amongst a convenience sample of healthcare workers providing HIV care in 89 health facilities in eight districts in Malawi. Burnout was measured using the Maslach Burnout Inventory. Anonymously administered surveys included questions about sociodemographics, work characteristics (work load, supervisor support, team interactions), depression, life stressors, assessment of type D personality, and career satisfaction. We performed univariable and multivariable regression analyses to explore associations between variables and burnout. Results: We received 535 responses (response rate 99%). Factors associated with higher rates of burnout on multivariable regression analyses included individual level factors: male gender (OR 1.75 [CI 1.17, 2.63]; p = 0.007), marital status (widowed or divorced) (OR 3.24 [CI 1.32, 7.98]; p = 0.011), depression (OR 3.32 [CI 1.21, 9.10]; p = 0.020), type D personality type (OR 2.77 [CI 1.50, 5.12]; p = 0.001) as well as work related factors: working at a health center vs. a rural hospital (OR 2.02 [CI 1.19, 3.40]; p = 0.009); lack of a very supportive supervisor (OR 2.38 [CI 1.32, 4.29]; p = 0.004), dissatisfaction with work/team interaction (OR 1.76 [CI 1.17, 2.66]; p = 0.007), and career dissatisfaction (OR 0.76 [CI 0.60, 0.96]; p = 0.020). Conclusion: This study identified several individual level vulnerabilities as well as work related modifiable factors. Improving the supervisory capacity of health facility managers and creating conditions for improved team dynamics may help reduce burnout amongst healthcare workers proving HIV care in Malawi. [ABSTRACT FROM AUTHOR]

Introduction: Mucosal immune activation, in the context of sexual transmission of HIV-1 infection, is crucial, as the increased presence of activated T cells enhance susceptibility to infection. In this regard, it has been proposed that immunomodulatory compounds capable of modulating immune activation, such as Vitamin D (VitD) may reduce HIV-1 transmission and might be used as a safe and cost-effective strategy for prevention. Considering this, we examined the in vitro effect of the treatment of peripheral blood mononuclear cells (PBMCs) with the active form of VitD, calcitriol, on cellular activation, function and susceptibility of CD4+ T cells to HIV-1 infection. Methods: We treated PBMCs from healthy HIV unexposed individuals (Co-HC) and frequently exposed, HIV-1 seronegative individuals (HESNs) from Colombia and from healthy non-exposed individuals from Canada (Ca-HC) with calcitriol and performed in vitro HIV-1 infection assays using X4- and R5-tropic HIV-1 strains respectively. In addition, we evaluated the activation and function of T cells and the expression of viral co-receptors, and select antiviral genes following calcitriol treatment. Results: Calcitriol reduced the frequency of infected CD4+ T cells and the number of viral particles per cell, for both, X4- and R5-tropic viruses tested in the Co-HC and the Ca-HC, respectively, but not in HESNs. Furthermore, in the Co-HC, calcitriol reduced the frequency of polyclonally activated T cells expressing the activation markers HLA-DR and CD38, and those HLA-DR+CD38-, whereas increased the subpopulation HLA-DR-CD38+. Calcitriol treatment also decreased production of granzyme, IL-2 and MIP-1β by T cells and increased the transcriptional expression of the inhibitor of NF-kB and the antiviral genes cathelicidin (CAMP) and APOBEC3G in PBMCs from Co-HC. Conclusion: Our in vitro findings suggest that VitD treatment could reduce HIV-1 transmission through a specific modulation of the activation levels and function of T cells, and the production of antiviral factors. In conclusion, VitD remains as an interesting potential strategy to prevent HIV-1 transmission that should be further explored. [ABSTRACT FROM AUTHOR]

HIV-1 replicates via a low-fidelity polymerase with a high mutation rate; strong conservation of individual nucleotides is highly indicative of the presence of critical structural or functional properties. Identifying such conservation can reveal novel insights into viral behaviour. We analysed 3651 publicly available sequences for the presence of nucleic acid conservation beyond that required by amino acid constraints, using a novel scale-free method that identifies regions of outlying score together with a codon scoring algorithm. Sequences with outlying score were further analysed using an algorithm for producing local RNA folds whilst accounting for alignment properties. 11 different conserved regions were identified, some corresponding to well-known cis-acting functions of the HIV-1 genome but also others whose conservation has not previously been noted. We identify rational causes for many of these, including cis functions, possible additional reading frame usage, a plausible mechanism by which the central polypurine tract primes second-strand DNA synthesis and a conformational stabilising function of a region at the 5′ end of env. [ABSTRACT FROM AUTHOR]

Background: The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3).Methods and Findings: In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28-36 weeks of gestation, age 26 (19-42), weight 67kg (45-119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3-8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum.Conclusion: Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy.Trial Registration: clinicaltrials.gov NCT02245022. [ABSTRACT FROM AUTHOR]

Background: Mental illness stigma is a fundamental barrier to improving mental health worldwide, but little is known about how to durably reduce it. Understanding of mental illness as a treatable medical condition may influence stigmatizing beliefs, but available evidence to inform this hypothesis has been derived solely from high-income countries. We embedded a randomized survey experiment within a whole-population cohort study in rural southwestern Uganda to assess the extent to which portrayals of mental illness treatment effectiveness influence personal beliefs and perceived norms about mental illness and about persons with mental illness.Methods and Findings: Study participants were randomly assigned to receive a vignette describing a typical woman (control condition) or one of nine variants describing a different symptom presentation (suggestive of schizophrenia, bipolar, or major depression) and treatment course (no treatment, treatment with remission, or treatment with remission followed by subsequent relapse). Participants then answered questions about personal beliefs and perceived norms in three domains of stigma: willingness to have the woman marry into their family, belief that she is receiving divine punishment, and belief that she brings shame on her family. We used multivariable Poisson and ordered logit regression models to estimate the causal effect of vignette treatment assignment on each stigma-related outcome. Of the participants randomized, 1,355 were successfully interviewed (76%) from November 2016 to June 2018. Roughly half of respondents were women (56%), half had completed primary school (57%), and two-thirds were married or cohabiting (64%). The mean age was 42 years. Across all types of mental illness and treatment scenarios, relative to the control vignette (22%-30%), substantially more study participants believed the woman in the vignette was receiving divine punishment (31%-54%) or believed she brought shame on her family (51%-73%), and most were unwilling to have her marry into their families (80%-88%). In multivariable Poisson regression models, vignette portrayals of untreated mental illness, relative to the control condition, increased the risk that study participants endorsed stigmatizing personal beliefs about mental illness and about persons with mental illness, irrespective of mental illness type (adjusted risk ratios [ARRs] varied from 1.7-3.1, all p < 0.001). Portrayals of effectively treated mental illness or treatment followed by subsequent relapse also increased the risk of responses indicating stigmatizing personal beliefs relative to control (ARRs varied from 1.5-3.0, all p < 0.001). The magnitudes of the estimates suggested that portrayals of initially effective treatment (whether followed by relapse or not) had little moderating influence on stigmatizing responses relative to vignettes portraying untreated mental illness. Responses to questions about perceived norms followed similar patterns. The primary limitations of this study are that the vignettes may have omitted context that could have influenced stigma and that generalizability beyond rural Uganda may be limited.Conclusions: In a population-based, randomized survey experiment conducted in rural southwestern Uganda, portrayals of effectively treated mental illness did not appear to reduce endorsement of stigmatizing beliefs about mental illness or about persons with mental illness. These findings run counter to evidence from the United States. Further research is necessary to understand the relationship between mental illness treatment and stigmatizing attitudes in Uganda and other countries worldwide.Trial Registration: The experimental procedures for this study were registered with ClinicalTrials.gov as "Measuring Beliefs and Norms About Persons With Mental Illness" (NCT03656770). [ABSTRACT FROM AUTHOR]

Introduction: Developing guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings. Methods: We use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies. Results: A policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%). Conclusions: These findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings. [ABSTRACT FROM AUTHOR]

Objective: Blood transfusion is the most frequently used and life-saving therapeutic procedure today. Transmission of virus, bacteria and parasitic microorganisms may occur due to transfusion (Transfusion transmitted infections-TTIs). Hepatitis B and C, human immunodeficiency virus (HIV) and syphilis (Treponema pallidum) bear the risk of transmission by transfusion. Hepatitis B surface antigen (HBsAg), anti-HCV, anti-HIV½ and syphilis antibody (VDRL: Venereal Disease Research Laboratory) are routinely controlled in all donated blood samples. The aim of the present study was to analyze the seroprevalence rates of blood donors through screening test results according to duration, age range and gender. Material and methods: Data of all blood donors obtained from blood Centre of Marmara University Pendik Training and Research Hospital between January 2013 and October 2018 were analyzed retrospectively. Serum samples of the donors were analyzed for HBsAg, anti-HCV, anti-HIV½ and VDRL. Test results of 114.240 donors were scanned. Gender, age range and distribution by years of these donors were analyzed. According to age distribution of donors were divided into 4 groups. Results: There were 114.240 participants including 106.153 (92.9%) males and 8.087 (7.1%) females. The positivity rate of HBsAg was detected 0.4% (36/8087) in females and 0.5% (500/106.153) in males. The positivity rate of anti-HCV was detected 0.4% (32/8.087) in females and 0.3% (344/106.153) in males. The positivity rate of anti HIV½ was 0.1% (9/8.087) in females and 0.1% (92/106.153) in males whereas the positivity rate of VDRL was 0.5% (41/8.087) in females and 0.3% (362/ 106.153) in males. Positivity rate for HBsAg and HCV were lower in the cases between 18 and 30 years of age. The positivity rates for anti-HIV½ was not significantly different according to the age range. Positivity rate for VDRL was higher in the cases at 51 years of age and older. Conclusion: No difference was found between men and women in terms of HBsAg, anti-HCV and anti-HIV½positivity. However, VDRL test positivity was significantly higher in female participants. Furthermore, HBsAg, anti-HCV and VDRL positivity rates increased by age. [ABSTRACT FROM AUTHOR]

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5–3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89–98%) in HIV-uninfected and of 100% (95% CI 79–100%) in HIV-infected children but low specificity: 7% (95% CI 6–8%) and 6% (95% CI 3–9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI—an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56–76%) and specificity of 46% (95% CI 44–48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35–84%) and a specificity of 42% (95% CI 36–48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit.Methods and Findings: SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median [IQR] age 34 [29-40] and CD4 count 286 [128-490]; 63% female) in South Africa and 477 patients in Kenya (median [IQR] age 35 [29-43] and CD4 count 283 [117-541]; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference [RD] [95% confidence interval (CI)] 10% [3%-17%]); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% [0.5%-11%]). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% [(2% to 14%]). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 [57%] of intervention-arm patients and 136/237 [57%] of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study.Conclusions: In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic.Trial Registration: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya. [ABSTRACT FROM AUTHOR]

There are different views on which of the two forms of viral spread is more efficient in vivo between cell-free and cell-associated virus. In this study, discrete time human immunodeficiency virus models are formulated and analysed with the goal of determining the form of viral spread that is more efficient in vivo. It is shown that on its own, cell-free viral spread cannot sustain an infection owing to the low infectivity of cell-free virus and cell-associated virus can sustain an infection because of the high infectivity of cell-associated virus. When acting concurrently, cell-associated virus is more efficient in spreading the infection upon exposure to the virus. However, in the long term, the two forms of viral spread contribute almost equally. Both forms of viral spread are shown to be able to initiate an infection. [ABSTRACT FROM AUTHOR]

Introduction: Mozambique continues to have a significant burden of HIV. Developing strategies to control the HIV epidemic remains a key priority for the Mozambican public health community. The primary aim of this study was to determine HIV prevalence and risk behavior among males and females screened for a HIV vaccine preparedness study in Maputo, Mozambique. Methods: Male and female participants between 18–35 years old were recruited from the general community and from female sex worker (FSW) and lesbian, gay, bisexual, and transgender (LGBT) associations in Maputo. All participants were screened for HIV and a questionnaire was administered to each participant to assess HIV risk behavior. Results: A total of 1125 adults were screened for HIV infection, among whom 506 (45%) were male. Among men, 5.7% reported having had sex with men (MSM) and 12% of female participants reported having exchanged sex for money, goods or favors in the past 3 months. The overall HIV prevalence was 10.4%; 10.7% of women, and 10.1% of men were HIV infected; 41.4% of MSM were seropositive. HIV infection was associated with older age (25–35 years old) (OR: 6.13, 95% CI: 3.01, 12.5), MSM (OR: 9.07, 95% CI: 3.85, 21.4), self-perception of being at high-risk for HIV (OR: 3.99, 95% CI: 1.27, 12.5) and self-report of a history of a diagnosis of sexually transmitted infection (OR: 3.75, 95% CI: 1.57, 8.98). Conclusion: In our cohort, HIV prevalence was much higher among MSM compared to the overall prevalence. Behavioral factors were found to be more associated with HIV prevalence than demographic factors. The study findings demonstrate the critical importance of directing services to minority communities, such as MSM, when prevention strategies are being devised for the general population. [ABSTRACT FROM AUTHOR]

Introduction: The success of antiretroviral treatment (ART) programs can be compromised by high rates of patient loss to follow-up (LTFU). We assessed the incidence and risk factors of LTFU in a large cohort of HIV-infected children receiving ART in Thailand. Methods: All children participating in a multicenter cohort (NCT00433030) between 1999 and 2014 were included. The date of LTFU was 9 months after the last contact date. ART interruption was defined as ART discontinuation for more than 7 days followed by resumption of treatment. Baseline and time-dependent risk factors associated with LTFU were identified using Fine and Gray competing risk regression models with death or referral to another hospital as competing events. Results: Of 873 children who were followed during a median of 8.6 years (interquartile range 4.5–10.6), 196 were LTFU, 73 died, and 195 referred. The cumulative incidence of LTFU was 2.9% at 1 year, 7.3% at 5 years and 22.2% at 10 years. Children aged 13 years and more had a 3-fold higher risk (95% confidence interval 2.06–4.78) of LTFU than those younger. Children who had interrupted ART within the previous year had a 2.5-fold higher risk (1.12–5.91) than those who had not. The risk of LTFU was lower in children stunted (height-for-age Z-scores <-2 SD) (0.42–0.96) or underweight (weight-for-age Z-scores <-2 SD) (0.24–0.97). Conclusion: Adolescence, ART interruption and absence of growth deficit were associated with LTFU. These may be warnings that should draw clinicians’ attention and possibly trigger specific interventions. Children with no significant growth retardation may also be at risk of LTFU. [ABSTRACT FROM AUTHOR]

Background: In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru. Methods: We conducted a secondary analysis of data from the 2011 Peruvian Biobehavioral Survey. Pearson’s Chi-squared test was used to identify individual-level characteristics associated with concurrency. We estimated the association between participant characteristics, concurrent partnerships, partnership type (stable vs. non-stable), and CLAI within the context of concurrent partnerships using multivariate and repeated-measure Poisson regression. Results: 3-month cumulative prevalence of concurrency was higher among TW compared to MSM (30.7% vs 25.2%, p = 0.014). Among those with concurrent stable and non-stable partners, 45% used condoms with both partners (95% CI: 40%-50%) and 30% preferentially had CLAI with the stable partner only (95%CI: 26%-35%). Factors associated with CLAI within the context of concurrent partnerships varied between MSM and TW. Conclusions: Although concurrency is common among TW and MSM in Peru, patterns of concurrency and differential condom use may vary between TW and MSM. Future research may explore differential condom use with stable and non-stable partners to better understand behavioral factors that may alter vulnerability to HIV in TW compared to MSM. [ABSTRACT FROM AUTHOR]

Laboratory assays for identifying recent HIV-1 infections are widely used for estimating incidence in cross-sectional population-level surveys in global HIV-1surveillance. Adequate assay and laboratory performance are required to ensure accurate incidence estimates. The NIAID-supported External Quality Assurance Program Oversight Laboratory (EQAPOL) established a proficiency testing program for the most widely-used incidence assay, the HIV-1 Limiting Antigen Avidity EIA (LAg), with US Centers for Disease Control and Prevention (CDC)-approved kits manufactured by Sedia Biosciences Corporation and Maxim Biomedical. The objective of this program is to monitor the performance of participating laboratories. Four rounds of blinded external proficiency (EP) panels were distributed to up to twenty testing sites (7 North American, 5 African, 4 Asian, 2 South American and 2 European). These panels consisted of ten plasma samples: three blinded well-characterized HIV-1-seropositive samples that were included as replicates and an HIV-negative control. The seropositive samples spanned the dynamic range of the assay and are categorized as either recent or long-term infection. Participating sites performed the assay according to manufacturers’ instructions and completed an online survey to gather information on kit manufacturer, lot of kit used, laboratory procedures and the experience of technicians. On average, fifteen sites participated in each round of testing, with an average of four sites testing with only the Maxim assay, seven testing with only the Sedia assay and five sites utilizing both assays. Overall, the Sedia and Maxim assays yielded similar infection status categorization across the laboratories; however, for most of the nine HIV+ samples tested, there were significant differences in the optical density readouts, ODn (N = 8) and OD (N = 7), between LAg kit manufacturers (p < 0.05 based on mixed effects models. The EQAPOL LAg program is important for monitoring laboratory performance as well as detecting variations between manufacturers of HIV-1incidence assays. [ABSTRACT FROM AUTHOR]

Background: In Côte d’Ivoire, people living with HIV (PLHIV) have free access to antiretroviral therapy (ART) and cotrimoxazole. Yet, they may use other medications to treat non-HIV diseases. Scarce data are available regarding the use of non-HIV medications in Africa. This study describes the use of non-HIV medications and identifies the factors associated with their use by PLHIV on ART in Côte d’Ivoire. Methods: A cross-sectional study was conducted in six HIV clinics in 2016. HIV-1-infected adults receiving ART for at least one year were eligible. A standardized questionnaire was used to collect demographics, HIV characteristics and medication use data. Associated factors were identified using a multivariate adjusted Poisson regression. Results: A total of 1,458 participants (74% women) were enrolled. The median age was 44 years, and the median duration of ART was 81 months. A total of 696 (48%) participants reported having used at least one non-HIV medication. Among the 1,519 non-HIV medications used, 550 (36%) had not been prescribed and 397 (26%) were from the nervous system class. Individuals who were more likely to report the use of at least one non-HIV medication included those who had been treated in an Abidjan HIV clinic, had a high school education level, had a monthly income between 152 and 304 euros, had a poor perceived health status, had WHO advanced clinical stage, had used traditional medicine products and had not used cotrimoxazole. Conclusion: Almost half PLHIV on ART reported using non-HIV medication. Further research is needed to assess whether the use of non-HIV medication is appropriate given about a third of those medications are not being prescribed. [ABSTRACT FROM AUTHOR]

The CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein is susceptible to multiple lineages of broadly neutralizing antibodies (bnAbs) that are attractive to elicit with vaccines. The CH235 lineage (VH1-46) of CD4bs bnAbs is particularly attractive because the most mature members neutralize 90% of circulating strains, do not possess long HCDR3 regions, and do not contain insertions and deletions that may be difficult to induce. We used virus neutralization to measure the interaction of CH235 unmutated common ancestor (CH235 UCA) with functional Env trimers on infectious virions to guide immunogen design for this bnAb lineage. Two Env mutations were identified, one in loop D (N279K) and another in V5 (G458Y), that acted synergistically to render autologous CH505 transmitted/founder virus susceptible to neutralization by CH235 UCA. Man5-enriched N-glycans provided additional synergy for neutralization. CH235 UCA bound with nanomolar affinity to corresponding soluble native-like Env trimers as candidate immunogens. A cryo-EM structure of CH235 UCA bound to Man5-enriched CH505.N279K.G458Y.SOSIP.664 revealed interactions of the antibody light chain complementarity determining region 3 (CDR L3) with the engineered Env loops D and V5. These results demonstrate that virus neutralization can directly inform vaccine design and suggest a germline targeting and reverse engineering strategy to initiate and mature the CH235 bnAb lineage. [ABSTRACT FROM AUTHOR]

Mother-to-child-transmission (MTCT) of human T-cell lymphotropic virus type-1(HTLV-1) contributes disproportionately to the burden of HTLV-1 associated diseases. All preventive measures to avoid MTCT rely on the identification of infected mothers. However, the impact of pregnancy on HTLV-1 diagnosis has not been clearly assessed. Paired samples from 21 HTLV-1 infected women taken during pregnancy and while not pregnant were analysed by CMIA and PCR. The signal-to-cut-off values (S/CO) were higher during pregnancy than in the paired non-pregnant samples. HTLV-1 proviral load did not alter significantly by pregnant state. S/CO positively correlated with HTLV proviral load. Pregnancy does not impair the diagnosis of HTLV-1/2, by either immunological (CMIA) or molecular (qPCR/nPCR) tests. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.Methods and Findings: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.Conclusion: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk. [ABSTRACT FROM AUTHOR]

Malawi’s Option B+ program is based on a ‘test and treat’ strategy that places all HIV-positive pregnant and lactating women on lifelong antiretroviral therapy. The steep increase in patient load placed severe pressure on a health system that has struggled for decades with inadequate supply of health care workers (HCWs) and poor infrastructure. We set out to explore health system barriers to Option B+ by asking HCWs in Malawi about their experiences treating pregnant and lactating women. We observed and conducted semi-structured interviews (SSIs) with 34 HCWs including nine expert clients (ECs) at 14 health facilities across Malawi, then coded and analyzed the data. We found that HCWs implementing Option B+ are so overburdened in Malawi that it reduces their ability to provide quality care to patients, who receive less counseling than they should, wait longer than is reasonable, and have very little privacy. Interventions that increase the number of HCWs and upgrade infrastructure to protect the privacy of HIV-infected pregnant and lactating women and their husbands could increase retention, but facilities will need to be improved to support men who accompany their partners on clinic visits. [ABSTRACT FROM AUTHOR]

Sexually Transmitted Infections (STIs) are ambiguous burden of tremendous health, social and economic consequences. The current systematic review was conducted in order to determine awareness and knowledge of Africans toward sexually transmitted infections, not only concerning HIV/AIDS, but also other STIs such as gonorrhea, syphilis, HBV, HCV and HPV. A systematic review of literature was conducted, studies were retrieved and selected after fulfilling the inclusion criteria as well as passing the assessment procedure. Related data was extracted, quantitative analysis was conducted among participants who responded to questions related to HIV, HBV, HCV, HPV or STIs knowledge, sensitivity analysis as well as subgroup analysis were also conducted. Seventy four articles addressing knowledge among 35 African countries were included and 136 questions were analyzed and synthesized. The question “does using condom reduces HIV transmission?” was answered by 1,316,873 Africans in 35 countries, 66.8% [95% Cl; 62.6, 70.9] answered yes. While the question “is sexual contact a possible route of HBV transmission?” was answered by 7,490 participants in 5 countries; 42.5% [95% Cl; 20.4, 64.7] answered yes. The differences observed among populations are highlighting the possibility for improvement by directing light toward specific populations as well as addressing specific awareness knowledge to ensure that the general as well as the related specific preventive knowledge is improved. [ABSTRACT FROM AUTHOR]

Introduction: Auditory processing disorders can negatively affect academic performance in children. They can result from a number of aetiologies, including the human immunodeficiency virus (HIV). Although studies in paediatrics are limited, research suggests that HIV-infected children display poorer auditory processing skills than uninfected children. Methods: The aims of this study were to scan the peer-reviewed literature on auditory processing skills in HIV-infected children, to describe how auditory processing was tested, how auditory processing skills were reported, and to identify gaps in current evidence. This systematic scoping review was conducted using a modified version of Arksey and O’Malley’s framework. Key words comprised ‘HIV’, ‘auditory processing’, ‘hearing’ and ‘child’. Electronic databases were searched for relevant articles published from 1 January 2000 to 30 April 2018, and reference lists of included studies were pearled. Two researchers reviewed the articles and extracted data on sample descriptors, auditory processing testing procedures, and auditory processing skills. A third author collated the results and resolved discrepancies. The American Speech-Language-Hearing Association description of auditory processing skills framed the analysis. Results: Five articles were included in this review (three from Brazil, one each from Mexico and Tanzania). Samples, and methods of testing were heterogeneous. Three studies reported on localization abilities, while gap detection thresholds, performance on dichotic tasks and speech discrimination scores were reported in one article each. No one study tested all areas of auditory processing skills and there was limited information about the auditory processing skills required for learning. Conclusion: This review highlighted the current sparse evidence-base for auditory processing in HIV-infected children. It identified the need to standardise testing procedures, measures of auditory processing skills, and sample selection. [ABSTRACT FROM AUTHOR]

High levels of undiagnosed and untreated HCV infection exist in prison populations globally. Prisons are a key location to identify, treat and prevent HCV infection among people who inject drugs (PWID). Understanding prisoners’ lived experiences of the HCV continuum of care informs how HCV care can be effectively delivered to this marginalised and high-risk population. This study aimed to explore Irish prisoners’ experience of prison and community-based HCV care. We conducted one-to-one interviews with 25 male prisoners with chronic HCV infection. Data collection and analysis was informed by grounded theory. The mean age of participants and first incarceration was 39.5 and 18.3 years respectively. The mean number of incarcerations was eight. The following themes were identified: medical and social factors influencing engagement (fear of treatment and lack of knowledge, HCV relevance and competing priorities), adverse impact of HCV on health and wellness, positive experience of prison life and health care and the transformative clinical and non-clinical changes associated with HCV treatment and cure. Findings suggest that prison release was associated with multiple stressors including homelessness and drug dependence which quickly eroded the health benefits gained during incarceration. The study generated a substantive theory of the need to increase the importance of HCV care among the routine competing priorities associated with the lives of PWID. HCV infected prisoners often lead complex lives and understanding their journeys through the HCV continuum can inform the development of meaningful HCV care pathways. Many challenges exist to optimising HCV treatment uptake in this group and incarceration is an opportunity to successfully engage HCV infected prisoners who underutilise and are underserved by community-based medical services. Support and linkage to care on release is essential to optimising HCV management. [ABSTRACT FROM AUTHOR]