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IntroductionThe use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region.MethodsA cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed.ResultsCognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3-98.7) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively.ConclusionFindings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.

IntroductionThe HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa. We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10-14) who are frequently left out of HIV interventions.MethodCommunity HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A "yes" response to one or more questions was classified as being "at risk" of being HIV-positive. Rapid HIV tests were offered to all children. Data were captured through an electronic data capture device from August 2016 to December 2017. The sensitivity, specificity, positive predictive value and negative predictive value were estimated for the screening tool, using the rapid HIV test result as the gold standard.ResultsIn our 14 study sites, 33,710 adolescents aged 10-14 in Zambia and 8,610 in South Africa participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in South Africa as "at risk". In Zambia the estimated sensitivity was 35.3% (95% CI 27.3%-44.2%) and estimated specificity was 88.9% (88.5%-89.2%). In South Africa the sensitivity was 72.3% (26.8%-94.9%) and specificity was 82.5% (81.6-83.4%).ConclusionThe sensitivity of the screening tool in a community setting in Zambia was low, so this tool should not be considered a substitute for universal testing where that is possible. In South Africa the sensitivity was higher, but with a wide confidence interval. Where universal testing is not possible the tool may help direct resources to adolescents more likely to be living with undiagnosed HIV.Trial registrationClinical Trial Number: NCT01900977.

BackgroundMental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15-19 years in Zambia and SA.MethodsWe conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country.ResultsOut of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-valueConclusionThe prevalence of depressive symptoms among adolescents ranged from 25-30% and was associated with increased HIV-risk behaviour.

Introduction To make valid comparisons across groups, a measurement instrument needs to be measurement invariant across those groups. The present study evaluates measurement invariance for experience of violence among adolescent girls and young women (AGYW) in two informal settlements in Nairobi, Kenya. Methods We used survey data collected from 1,081 AGYW aged 15–22 years from two Nairobi’s informal settlements of Korogocho (n = 617) and Viwandani (n = 464) in 2017 through DREAMS (an initiative aimed at reducing HIV incidence among AGYW with a core package of evidence-based interventions) impact evaluation project. Experience of violence was measured using the 15-item WHO’s violence against women instrument, and factorial (non)invariance assessed within exploratory structural equation modeling (ESEM) framework. Cross-group measurement invariance was assessed using Bayesian Multiple Indicator Multiple Causes (MIMIC) model across site, age groups, self-reported invitation to participate in DREAMS, marital status, currently in school, education level, religion, ethnic groups, ever had sex, slept hungry at night past 4 weeks, and wealth index. Results The mean and median ages of the AGYW were 17.9 years and 17 years, respectively. About 59% reported having had sex and 58% of AGYW were in school. The percentage reporting each act of violence varied from 1.6% (“attacked you with a weapon”) to 26.5% (“insult you or make you feel bad about yourself”). About 44% (n = 474) of participants experienced ≥1 acts of violence, and 2.7% (n = 29) experienced at least half of the 15 acts. The structure underlying the 15 items was configurally similar to that proposed by WHO, with three factors reflecting either psychological, physical, or sexual violence. Noninvariance was detected for five items—spread across the three domains. Three of five items showed noninvariance only for sleeping hungry at night in the past 4 weeks. As the majority of items did not show evidence of noninvariance, differences in latent mean scores likely reflect actual differences and may not be attributable to measurement artifacts. Conclusions Using state-of-the-art statistical techniques on a widely used instrument for measuring exposure to violence among women, this study provides support for the subscales of psychological, physical and sexual violence in a Kenyan AGYW population. The instrument supports comparisons across groups within this population. This is crucial when comparing violence against girls/women prevalence rates and to understand challenges and exchange strategies to reduce abuse or violence experienced by AGYW, or women in general.

BackgroundDREAMS promotes a comprehensive HIV prevention approach to reduce HIV incidence among adolescent girls and young women (AGYW). One pathway that DREAMS seeks to impact is to support AGYW to stay in school and achieve secondary education. We assessed the impact of DREAMS on educational outcomes among AGYW in Nairobi, Kenya.Methods and findingsIn two informal settlements in Nairobi, 1081 AGYW aged 15-22 years were randomly selected in 2017 and followed-up to 2019. AGYW reporting invitation to participate in DREAMS during 2017-18 were classified as "DREAMS beneficiaries". Our main outcome was being in school and/or completed lower secondary school in 2019. We used multivariable logistic regression to quantify the association between being a DREAMS beneficiary and the outcome; and a causal inference framework to estimate proportions achieving the outcome if all, versus no, AGYW were DREAMS beneficiaries, adjusting for the propensity to be a DREAMS beneficiary. Of AGYW enrolled in 2017, 79% (852/1081) were followed-up to 2019. In unadjusted analysis, DREAMS beneficiaries had higher attainment than non-beneficiaries (85% vs 75% in school or completed lower secondary school, Odds Ratio (OR) = 1.9; 95%CI: 1.3,2.8). The effect weakened with adjustment for age and other confounders, (adjusted OR = 1.4; 95%CI: 0.9,2.4). From the causal analysis, evidence was weak for an impact of DREAMS (estimated 83% vs 79% in school or completed lower secondary school, if all vs no AGYW were beneficiaries, difference = 4%; 95%CI: -2,11%). Among AGYW out of school at baseline, the estimated differences were 21% (95%CI: -3,43%) among 15-17 year olds; and 4% (95%CI: -8,17%) among 18-22 year olds.ConclusionsDREAMS had a modest impact on educational attainment among AGYW in informal settlements in Kenya, by supporting both retention and re-enrolment in school. Larger impact might be achieved if more AGYW were reached with educational subsidies, alongside other DREAMS interventions.

IntroductionWe sought to estimate the prevalence, severity and identify predictors of violence among adolescent girls and young women (AGYW) in informal settlement areas of Nairobi, Kenya, selected for DREAMS (Determined Resilient Empowered AIDS-free, Mentored and Safe) investment.MethodsData were collected from 1687 AGYW aged 10-14 years (n = 606) and 15-22 years (n = 1081), randomly selected from a general population census in Korogocho and Viwandani in 2017, as part of an impact evaluation of the "DREAMS" Partnership. For 10-14 year-olds, we measured violence experienced either in the past 6 months or ever using a different set of questions from those used for 15-22 year-olds. Among 15-22 year-olds we measured prevalence of violence, experienced in the past 12 months, using World Health Organization (WHO) definitions for violence typologies. Predictors of violence were identified using multivariable logit models.ResultsAmong 606 girls aged 10-14 years, about 54% and 7% ever experienced psychological and sexual violence, respectively. About 33%, 16% and 5% experienced psychological, physical and sexual violence in the past 6 months. The 10-14 year old girls who engaged in chores or activities for payment in the past 6 months, or whose family did not have enough food due to lack of money were at a greater risk for violence. Invitation to DREAMS and being a non-Christian were protective. Among 1081 AGYW aged 15-22 years, psychological violence was the most prevalent in the past year (33.1%), followed by physical violence (22.9%), and sexual violence (15.8%). About 7% experienced all three types of violence. Severe physical violence was more prevalent (13.8%) than moderate physical violence (9.2%). Among AGYW aged 15-22 years, being previously married/lived with partner, engaging in employment last month, food insecure were all risk factors for psychological violence. For physical violence, living in Viwandani and being a Muslim were protective; while being previously married or lived with a partner, or sleeping hungry at night during the past 4 weeks were risk factors. The odds of sexual violence were lower among AGYW aged 18-22 years and among Muslims. Engaging in sex and food insecurity increased chances for sexual violence.ConclusionsPrevalence of recent violence among AGYW is high in this population. This calls for increased effort geared towards addressing drivers of violence as an early entry point of HIV prevention effort in this vulnerable group.

BackgroundYoung men are less likely than young women to engage with HIV prevention and care, and their HIV-related mortality is higher. We describe HIV incidence and uptake of HIV services in men 20-29 years(y) in rural KwaZulu-Natal, South Africa, before the roll-out of DREAMS.MethodsWe used data from a population-based demographic and HIV surveillance cohort. HIV incidence was estimated from anonymised testing in an annual serosurvey. Service uptake was assessed in 2011 and 2015, through two self-reported outcomes: 1) HIV testing in the past 12 months(m); 2) voluntary medical male circumcision(VMMC). Logistic regression was used to estimate odds ratios(OR) and 95% confidence intervals(CI) for factors associated with each outcome.ResultsHIV incidence in 2011-2015 was 2.6/100 person-years (95%CI = 2.0-3.4) and 4.2 (95%CI = 3.1-5.6) among men 20-24y and 25-29y, respectively, with no significant change from 2006-2010. N = 1311 and N = 1221 young men participated in the 2011 and 2015 surveys, respectively. In both years, 1 partner in the past 12m, or condom use at last sex, but lower in those reporting a casual partner (adjusted (a)OR = 0.53, 95%CI = 0.37-0.75). VMMC uptake was associated with survey year and higher education. Men aged 25-29y and those who were employed (aOR = 0.66; 95%CI = 0.49-0.89) were less likely to report VMMC.ConclusionsHIV incidence in men 20-29y was very high, and pre-exposure prophylaxis (PrEP) should be considered in this population. Uptake of services was low. VMMC coverage increased dramatically from 2011 to 2015, especially among younger men, suggesting a demand for this service. Interventions designed with and for young men are urgently needed.

BackgroundThe 'DREAMS Partnership' promotes a multi-sectoral approach to reduce adolescent girls and young women's (AGYW) vulnerability through a core package of interventions targeting multiple sources of HIV risk-to promote Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) lives. Implementation of such multi-sectoral programmes is complex and requires adaptation to national and local contexts. We describe the early implementation of DREAMS in diverse settings, to identify lessons for the scale-up and replication of combination programmes for young people.MethodsAs part of evaluations underway in six DREAMS sites in three countries (Kenya, South Africa and Zimbabwe), we draw on process evaluation data collected from focus group discussions, key informant interviews, and in-depth interviews with beneficiaries, parents/caregivers, programme managers and opinion leaders. Additionally, structured observations were conducted and Gantt charts completed upon consultation with implementers. We concurrently reviewed documentation available on DREAMS and held cross-site discussions to interpret findings.FindingsAll sites sought to implement all components of the DREAMS core package, but how and when they were implemented varied by context. Models of delivery differed, with either multiple or single partners responsible for some or all interventions. Key challenges included the urgent and ambitious expectations of DREAMS; 'layering' multiple interventions across different sectors (health, education, social welfare); supporting individuals' journeys between services to improve uptake and retention; engaging communities beyond direct beneficiaries; avoiding perceived/actual exclusivity; and ensuring continuity of commitment and funding for DREAMS. Despite significant challenges, DREAMS was well-received in the communities and perceived by both beneficiaries and implementers to empower AGYW to remain HIV negative. Structures, protocols and tools were introduced to strengthen referrals and deliver services targeted to the age and circumstances of young people.ConclusionsThe benefits of combinations or integrated 'packages' of interventions are increasingly recognised. Early implementation of DREAMS provides useful lessons for improving coordination across multiple partners using a phased, systematic approach, regular adaptions to each unique context, and ensuring community ownership.

BACKGROUND:The DREAMS (Determined Resilient Empowered AIDS-free, Mentored and Safe) Partnership aims to reduce HIV incidence among adolescent girls and young women (AGYW,15-24y) with a core package of evidence-based interventions. Some interventions, including voluntary HIV counselling and testing and circumcision, will be targeted at the male sexual partners of AGYW. A priority of DREAMS is to characterise the male partners for effective targeting. METHODS:Using population-based data (2010-2015) in three DREAMS impact evaluation settings in Kenya and South Africa, we describe the demographic characteristics and sexual behaviour of male partners reported by AGYW, and the characteristics of males who report sexual activity with AGYW. RESULTS:In all settings, over 90% of recent male partners reported by AGYW were aged

Young women (aged 15-24) who exchange sex for money or other support are among the highest risk groups for HIV acquisition, particularly in high prevalence settings. To prepare for introduction and evaluation of the DREAMS programme in Zimbabwe, which provides biomedical and social interventions to reduce adolescent girls' and young women's HIV vulnerability, we conducted a rapid needs assessment in 6 towns using a "social mapping" approach. In each site, we talked to adult sex workers and other key informants to identify locations where young women sell sex, followed by direct observation, group discussions and interviews. We collected data on socio-demographic characteristics of young women who sell sex, the structure and organisation of their sexual exchanges, interactions with each other and adult sex workers, and engagement with health services. Over a two-week period, we developed a "social map" for each study site, identifying similarities and differences across contexts and their implications for programming and research. Similarities include the concentration of younger women in street-based venues in town centres, their conflict with older sex workers due to competition for clients and acceptance of lower payments, and reluctance to attend existing services. Key differences were found in the 4 university towns included in our sample, where female students participate in diverse forms of sexual exchange but do not identify themselves as selling sex. In smaller towns where illegal gold panning or trucking routes were found, young women migrated in from surrounding rural areas specifically to sell sex. Young women who sell sex are different from each other, and do not work with or attend the same services as adult sex workers. Our findings are being used to inform appropriate intervention activities targeting these vulnerable young women, and to identify effective strategies for recruiting them into the DREAMS process and impact evaluations.

BACKGROUND:Adolescent girls and young women (AGYW) bear the brunt of the HIV epidemic in South Africa. 'DREAMS' aims to reduce HIV incidence through multi-level combination prevention. We describe HIV incidence and uptake of HIV and sexual reproductive health (SRH) by AGYW in KwaZulu-Natal (KZN), prior to DREAMS. METHODS:Longitudinal and cross-sectional analysis of women (15-24 year old) in a population-based HIV incidence cohort within a demographic surveillance site in KZN. Observation time for HIV incidence was person-years at risk while resident. "Current use of contraceptives" and "having an HIV test in the past 12 months" was compared between 2011 and 2015. RESULTS:In 2015, HIV prevalence was 11.0% and 34.1% and HIV incidence (2011-2015) was 4.54% (95%CI:3.89-5.30) and 7.45% (95%CI:6.51-8.51) per year in 15-19 and 20-24 year olds respectively, with no significant decline compared to 2006-2010. In 2015, 90.7% of 20-24-year-olds were unemployed, 36.4% and 51.7% of 15-19 and 20-24 year olds reported recent migration; 20.9% and 72.6% of 15-19 and 20-24 year olds had ever been pregnant. In 2015, less than 50% reported condom-use at last sex, 15.0% of 15-19 year olds and 48.9% of 20-24 year olds were currently using contraception and 32.0% and 66.7% of 15-19 and 20-24 year olds had tested for HIV in the past 12 months. There had been no improvement compared to 2011. Factors associated with AGYW testing for HIV in the past 12 months were, survey year-2011 more likely than 2015 (aOR = 0.50), number of partners (aOR = 3.25), ever been pregnant (aOR = 2.47) and knowing where to find ART (aOR = 1.54). Factors associated with contraception use were being older (aOR = 4.83); ever been pregnant (aOR = 12.62); knowing where to get ART (aOR = 1.79) and having had an HIV test in past 12 months (aOR = 1.74). CONCLUSION:Prior to DREAMS, HIV incidence in AGYW was high. HIV and SRH service uptake did not improve and was suboptimal. Findings highlight the need for combination HIV prevention programmes for AGYW in this economically vulnerable area.

INTRODUCTION:High incidence of HIV infection among adolescent girls and young women (AGYW) has been attributed to the numerous and often layered vulnerabilities that they encounter including violence against women, unfavourable power relations that are worsened by age-disparate sexual relations, and limited access to sexual and reproductive health information and services. For AGYW living in urban informal settlements (slums), these vulnerabilities are compounded by pervasive poverty, fragmented social networks, and limited access to social services including health and education. In this paper, we assess sexual risk behaviours and their correlates among AGYW in two slum settlements in Nairobi, Kenya, prior to the implementation of interventions under the Determined Resilient Empowered AIDS-free Mentored and Safe (DREAMS) Partnership. METHODS:We drew on secondary data from the Transition to Adulthood study, the most recent representative study on adolescent sexual behaviour in the two settlements. The study was nested within the Nairobi Urban Health and Demographic Surveillance System (NUHDSS). Data were collected in 2009 from 1,390 AGYW aged 12-23 years. We estimated the proportions of AGYW reporting ever tested for HIV, condom use, multiple sexual partners and age-disparate sex by socio-demographic characteristics. "High risk" sexual behaviour was defined as a composite of these four variables and age at first sex. Multivariable regression analyses were performed to identify factors associated with risk behaviours. RESULTS:Fifty-one percent of AGYW reported that they had ever tested for HIV and received results of their last test, with the proportion rising steeply by age (from 15% to 84% among those

INTRODUCTION:WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. METHODS:All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as 'being three or more months late for an antiretroviral pharmacy pick-up appointment'. All clients were followed until attrition, transfer out or end May 2016. RESULTS:A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195-468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8-42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0-500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. CONCLUSIONS:Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries.

BACKGROUND:HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the "PopART" universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. METHODS AND FINDINGS:The second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used "time-to-event" methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs' electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+ status, ~80% of both men and women were on ART by the end of R2, close to 90% among men aged ≥45 and women aged ≥35 years, but lower among younger adults, those who were resident in R1 but did not participate in R1, and those who were newly resident in the area of the community in which they were living in R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women, compared with the cumulative 90-90 target of 81%. Among those who reported ever taking ART, 93% of men and 95% of women self-reported they were on ART and missed 0 pills in the last 3 days. The median time to start ART after referral to care was ~6 months in R2, similar across the age range 25-54 years, compared with ~9.5 months in R1. The two main limitations to our findings were that a comparison with control-arm communities cannot be made until the end of the study; and that to extrapolate to the total population, assumptions were required about individuals who were resident, but did not participate, in R2. CONCLUSIONS:Overall coverage against the 90-90 targets was high after two years of intervention, but was lower among men, individuals aged 18-34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements.

INTRODUCTION:We aimed to establish how effective community-based HIV testing services (HTS), including home and community location based (non-health facility) HIV testing services (HB-/CLB-HTS), are in improving care in sub-Saharan Africa (SSA), with a view to achieving the 90-90-90 targets. METHODS:We conducted a systematic review of published literature from 2007-17 which reported on the proportion of individuals who link-to-care and/or initiate ART after detection with HIV through community-based testing. A meta-analysis was deemed inappropriate due to heterogeneity in reporting. RESULTS AND DISCUSSION:Twenty-five care cascades from 6 SSA countries were examined in the final review- 15 HB-HTS, 8 CLB-HTS, 2 combined HB-/CLB-HTS. Proportions linked-to-care over 1-12 months ranged from 14-96% for HB-HTS and 10-79% for CLB-HTS, with most studies reporting outcomes over short periods (3 months). Fewer studies reported ART-related outcomes following community-based testing and most of these studies included

The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.

BackgroundThe HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) are brief tools that have been developed to screen for and aid diagnosis of HIV-associated dementia (HAD). They are increasingly being used in clinical practice for minor neurocognitive disorder (MND) as well as HAD, despite uncertainty about their accuracy.Methods and findingsA systematic review of the accuracy of the HDS and IHDS was conducted. Studies were assessed on Standards for Reporting Diagnostic Accuracy criteria. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios (DOR) were calculated for each scale as a test for HAD or MND. We retrieved 15 studies of the HDS, 10 of the IHDS, and 1 of both scales. Thirteen studies of the HDS were conducted in North America, and 7 of the IHDS studies were conducted in sub-Saharan Africa. Estimates of accuracy were highly heterogeneous between studies for the HDS but less so for the IHDS. Pooled DOR for the HDS was 7.52 (95% confidence interval 3.75-15.11), sensitivity and specificity for HAD were estimated at 68.1% and 77.9%, and sensitivity and specificity for MND were estimated at 42.0% and 91.2%. Pooled DOR for the IHDS was 3.49 (2.12-5.73), sensitivity and specificity for HAD were 74.3% and 54.7%, and sensitivity and specificity for MND were 64.3% and 66.0%.ConclusionBoth scales were low in accuracy. The literature is limited by the lack of a gold standard, and variation in estimates of accuracy is likely to be due to differences in reference standard. There is a lack of studies comparing both scales, and they have been studied in different populations, but the IHDS may be less specific than the HDS. These rapid tests are not recommended for diagnostic use, and further research is required to inform their use in asymptomatic screening.

In South Africa the estimated incidence of all forms of tuberculosis (TB) for 2008 was 960/100000. It was reported that all South Africans lived in districts with Directly Observed Therapy, Short-course. However, the 2011 WHO report indicated South Africa as the only country in the world where the TB incidence is still rising.To report the results of a TB prevalence survey and to determine the speed of TB case detection in the study communities.In 2005 a TB prevalence survey was done to inform the sample size calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It was a cluster survey with clustering by enumeration area; all households were visited within enumeration areas and informed consent obtained from eligible adults. A questionnaire was completed and a sputum sample collected from each adult. Samples were inoculated on both liquid mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen media. A follow-up HIV prevalence survey was done in 2007.In Community A, the adjusted prevalence of culture positive TB was 32/1000 (95%CI 25-41/1000) and of smear positive TB 8/1000 (95%CI 5-13/1000). In Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI 17-32/1000) and of smear positive TB 9/1000 (95%CI 6-15/1000). In Community A the patient diagnostic rate was 0.38/person-year while in community B it was 0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19-30%).In both communities a higher TB prevalence than national estimates and a low patient diagnostic rate was calculated, suggesting that cases are not detected at a sufficient rate to interrupt transmission. These findings may contribute to the rising TB incidence in South Africa. The TB epidemic should therefore be addressed rapidly and effectively, especially in the presence of the concurrently high HIV prevalence.

CONTEXT:Knowledge of HIV status may influence fertility desires of married men and women. There is little knowledge about the importance of this influence among monogamously married couples and how knowledge of HIV status influences use of contraception among these couples. METHODOLOGY:We carried out a cross-sectional analysis of interview data collected between October 2008 and September 2009 on men aged 15-59 years and women aged 15-49 years who formed 1766 monogamously married couples within the Karonga Prevention Study demographic surveillance study in northern Malawi. RESULTS:5% of men and 4% of women knew that they were HIV positive at the time of interview and 81% of men and 89% of women knew that they were HIV negative. 73% of men and 83% of women who knew that they were HIV positive stated that they did not want more children, compared to 35% of men and 38% of women who knew they were HIV negative. Concordant HIV positive couples were more likely than concordant negative couples to desire to stop child bearing (odds ratio 11.5, 95%CI 4.3-30.7, after adjusting for other factors) but only slightly more likely to use contraceptives (adjusted odds ratio 1.5 (95%CI 0.8-3.3). CONCLUSION:Knowledge of HIV positive status is associated with an increase in the reported desire to cease childbearing but there was limited evidence that this desire led to higher use of contraception. More efforts directed towards assisting HIV positive couples to access and use reproductive health services and limit HIV transmission among couples are recommended.

BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OH)D concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants.Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47) and 12 (n = 37) months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively), as a control group. Plasma vitamin D concentrations (25(OH)D) were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb) PPD for 6 days.58% of infants had some level of hypovitaminosis (25(OH)D

Sexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.All consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.We have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population.

Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3-3.9) and never being married (adjusted OR 4.1, 95% CI1.5-11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15-0.63), compared to those with no dependent children.Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.A cross-sectional sexual behaviour survey was conducted on all individuals age 15-59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25(th) centile was used to define "early" sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (

Four studies from sub-Saharan Africa have found a substantial population-level effect of ART provision on adult mortality. It is important to see if the impact changes with time since the start of treatment scale-up, and as treatment moves to smaller clinics.During 2002-4 a demographic surveillance site (DSS) was established in Karonga district, northern Malawi. Information on births and deaths is collected monthly, with verbal autopsies conducted for all deaths; migrations are updated annually. We analysed mortality trends by comparing three time periods: pre-ART roll-out in the district (August 2002-June 2005), ART period 1 (July 2005-September 2006) when ART was available only in a town 70 km away, and ART period 2 (October 2006-September 2008), when ART was available at a clinic within the DSS area. HIV prevalence and ART uptake were estimated from a sero-survey conducted in 2007/2008. The all-cause mortality rate among 15-59 year olds was 10.2 per 1000 person-years in the pre-ART period (288 deaths/28285 person-years). It fell by 16% in ART period 1 and by 32% in ART period 2 (95% CI 18%-43%), compared with the pre-ART period. The AIDS mortality rate fell from 6.4 to 4.6 to 2.7 per 1000 person-years in the pre-ART period, period 1 and period 2 respectively (rate ratio for period 2 = 0.43, 95% CI 0.33-0.56). There was little change in non-AIDS mortality. Treatment coverage among individuals eligible to start ART was around 70% in 2008.ART can have a dramatic effect on mortality in a resource-constrained setting in Africa, at least in the early years of treatment provision. Our findings support the decentralised delivery of ART from peripheral health centres with unsophisticated facilities. Continued funding to maintain and further scale-up treatment provision will bring large benefits in terms of saving lives.

As HIV-related deaths increase in a population the usual association between low socioeconomic status and child mortality may change, particularly as death rates from other causes decline.As part of a demographic surveillance system in northern Malawi in 2002-6, covering a population of 32,000, information was collected on socio-economic status of the households. Deaths were classified as HIV/AIDS-related or not by verbal autopsy. Poisson regression models were used to assess the association of socio-economic indicators with all-cause mortality, AIDS-mortality and non-AIDS mortality among children. There were 195 deaths in infants, 109 in children aged 1-4 years, and 38 in children aged 5-15. All-cause child mortality in infants and 1-4 year olds was similar in households with higher and lower socio-economic status. In infants 13% of deaths were attributed to AIDS, and there were no clear trends with socio-economic status for AIDS or non-AIDS causes. For 1-4 year olds 27% of deaths were attributed to AIDS. AIDS mortality was higher among those with better built houses, and lowest in those with income from farming and fishing, whereas non-AIDS mortality was higher in those with worse built houses, lowest in those with income from employment, and decreased with increasing household assets.In this population, since HIV infection among adults was initially more common among the less poor, childhood mortality patterns have changed. The usual gap in survival between the poor and the less poor has been lost, but because the less poor have been disproportionately affected by HIV, rather than because of relative improvement in the survival of the poorest.

The World Health Organization (WHO) released new Child Growth Standards in 2006 to replace the current National Center for Health Statistics (NCHS) growth reference. We assessed how switching from the NCHS to the newly released WHO Growth Standards affects the estimated prevalence of wasting, underweight and stunting, and the pattern of risk factors identified.Data were drawn from a village-informant driven Demographic Surveillance System in Northern Malawi. Children (n = 1328) were visited twice at 0-4 months and 11-15 months. Data were collected on the demographic and socio-economic environment of the child, health history, maternal and child anthropometry and child feeding practices. Weight-for-length, weight-for-age and length-for-age were derived in z-scores using the two growth references. In early infancy, prevalence estimates were 2.9, 6.1, and 8.5 fold higher for stunting, underweight, and wasting respectively using the WHO standards compared to NCHS reference (p

Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa.A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele.This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.