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1.

Introduction

Most African countries perform infant HIV testing at 6 weeks or later. The addition of targeted testing at birth may improve retention in care, treatment outcomes and survival for HIV‐infected infants.

Methods

HIV‐exposed infants were screened as part of the Early Infant Treatment (EIT) study in Botswana. Screened infants were ≥35 weeks gestational age and ≥2000 g at birth. Risk factors for mother‐to‐child transmission (MTCT) were assessed by maternal obstetric card or verbally. Risk factors included <8 weeks ART in pregnancy, last known CD4 <250 cells/mm3, last known HIV RNA >400 copies/mL, poor maternal ART adherence, lack of maternal zidovudine (ZDV) in labour, or lack of infant post‐exposure prophylaxis. Infants underwent dried blood spot testing by Roche Cobas Ampliprep/Cobas Taqman HIV‐1 qualitative PCR.

Results

From April 2015 to April 2016, 2303 HIV‐exposed infants were tested for HIV in the EIT study. Of these, 369 (16%) were identified as high risk for HIV infection by information available at birth, and 12 (0.5% overall, 3.25% of high risk) were identified as HIV positive at birth. All 12 positive infants were identified as high risk at the time of screening, and only 2 risk factors were required to identify all positive infants: either <8 weeks of maternal ART in pregnancy (75%) or lack of maternal HIV suppression at last test (25%).

Conclusions

In utero MTCT occurred only among infants identified as high risk at delivery, using information available from the mother or obstetric record. Birth testing that targets high‐risk infants based on maternal ART receipt is likely to identify the majority of in utero HIV transmissions, and allows early ART initiation for these infants.
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2.

Introduction

In 2010, the WHO recommended women living with HIV breastfeed for 12 months while taking antiretroviral therapy (ART) to balance breastfeeding benefits against HIV transmission risks. To inform the 2016 WHO guidelines, we updated prior research on the impact of breastfeeding duration on HIV‐free infant survival (HFS) by incorporating maternal ART duration, infant/child mortality and mother‐to‐child transmission data.

Methods

Using the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐Infant model, we simulated the impact of breastfeeding duration on 24‐month HFS among HIV‐exposed, uninfected infants. We defined “optimal” breastfeeding durations as those maximizing 24‐month HFS. We varied maternal ART duration, mortality rates among breastfed infants/children, and relative risk of mortality associated with replacement feeding (“RRRF”), modelled as a multiplier on all‐cause mortality for replacement‐fed infants/children (range: 1 [no additional risk] to 6). The base‐case simulated RRRF = 3, median infant mortality, and 24‐month maternal ART duration.

Results

In the base‐case, HFS ranged from 83.1% (no breastfeeding) to 90.2% (12‐months breastfeeding). Optimal breastfeeding durations increased with higher RRRF values and longer maternal ART durations, but did not change substantially with variation in infant mortality rates. Optimal breastfeeding durations often exceeded the previous WHO recommendation of 12 months.

Conclusions

In settings with high RRRF and long maternal ART durations, HFS is maximized when mothers breastfeed longer than the previously‐recommended 12 months. In settings with low RRRF or short maternal ART durations, shorter breastfeeding durations optimize HFS. If mothers are supported to use ART for longer periods of time, it is possible to reduce transmission risks and gain the benefits of longer breastfeeding durations.
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3.

Introduction

Dolutegravir (DTG)‐based antiretroviral therapy (ART) is recommended for first‐line HIV treatment in the US and Europe. Efavirenz (EFV)‐based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG‐based first‐line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count.

Methods

We used a microsimulation of HIV disease, the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐International model, to project outcomes in ART‐naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC. Regimen‐specific inputs, including virologic suppression at 48 weeks (SOC: 82% vs. DTG: 90%) and annual costs ($98 vs. $102), were informed by clinical trial data and other sources and varied widely in sensitivity analysis. We compared incremental cost‐effectiveness ratios (ICERs), measured in $/year of life saved (YLS), to India's per capita gross domestic product ($1600 in 2015). We compared the budget impact and HIV transmission effects of the two strategies for the estimated 444,000 and 916,000 patients likely to initiate ART in India over the next 2 and 5 years.

Results

Compared to SOC, DTG improved 5‐year survival from 76.7% to 83.0%, increased life expectancy from 22.0 to 24.8 years (14.0 to 15.5 years, discounted), averted 13,000 transmitted HIV infections over 5 years, increased discounted lifetime care costs from $3040 to $3240, and resulted in a lifetime ICER of $130/YLS, less than 10% of India's per capita GDP in 2015. DTG maintained an ICER below 50% of India's per capita GDP as long as the annual three‐drug regimen cost was ≤$180/year. Over a 2‐ or 5‐year horizon, total undiscounted outlays for HIV‐related care were virtually the same for both strategies.

Conclusions

A generic DTG‐based regimen is likely to be cost‐effective and should be recommended for initial therapy of HIV infection in India.
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4.

Introduction

HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART.

Methods

A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression.

Results

Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC).

Conclusions

We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508.
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5.

Introduction

Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV ‐infected patients in non‐clinical trial settings in Asian countries.

Methods

The study population consisted of HIV ‐infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD ). Individuals were included in this analysis if they started combination antiretroviral treatment (cART ) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART . The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within‐class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.

Results

Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.

Conclusions

The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non‐clinical trial settings in Asian countries.
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6.

Introduction

Many prevention of mother‐to‐child HIV transmission programmes across Africa initiate HIV‐infected (HIV positive) pregnant women on lifelong antiretroviral therapy (ART) on the first day of antenatal care (“same‐day” initiation). However, there are concerns that same‐day initiation may limit patient preparation before starting ART and contribute to subsequent non‐adherence, disengagement from care and raised viral load. We examined if same‐day initiation was associated with viral suppression and engagement in care during pregnancy.

Methods

Consecutive ART‐eligible pregnant women making their first antenatal care (ANC) visit at a primary care facility in Cape Town, South Africa were enrolled into a prospective cohort between March 2013 and June 2014. Before July 2013, ART eligibility was based on CD4 cell count ≤350 cells/μL (“Option A”), with a 1 to 2 week delay from the first ANC visit to ART initiation for patient preparation; thereafter all women were eligible regardless of CD4 cell count (“Option B+”) and offered ART on the same day as first ANC visit. Women were followed with viral load testing conducted separately from routine ART services, and engagement in ART services was measured using routinely collected clinic, pharmacy and laboratory records through 12 months postpartum.

Results

Among 628 HIV‐positive women (median age, 28 years; median gestation at ART start, 21 weeks; 55% newly diagnosed with HIV), 73% initiated ART same‐day; this proportion was higher under Option B+ versus Option A (85% vs. 20%). Levels of viral suppression (viral load <50 copies/mL) at delivery (74% vs. 82%) and 12 months postpartum (74% vs. 71%) were similar under same‐day versus delayed initiation respectively. Findings were consistent when viral suppression was defined at <1000 copies/mL, after adjustment for demographic/clinical measures and across subgroups of age, CD4 and timing of HIV diagnosis. Time to first viral rebound following initial suppression did not differ by timing of ART initiation nor did engagement in care through 12 months postpartum (same‐day = 73%, delayed = 73%, p = 0.910).

Conclusions

These data suggest that same‐day ART initiation during pregnancy is not associated with lower levels of engagement in care or viral suppression through 12 months post‐delivery in this setting, providing reassurance to ART programmes implementing Option B+.
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7.

Introduction

Screening of modifiable cardiovascular disease (CVD) risk factors is recommended but not routinely provided for HIV‐infected patients, especially in low‐resource settings. Potential concerns include limited staff time and low patient acceptability, but little empirical data exists. As part of a pilot study of screening in a large urban HIV clinic in Swaziland, we conducted a time‐motion study to assess the impact of screening on patient flow and HIV service delivery and exit interviews to assess patient acceptability.

Methods

A convenience sample of patients ≥40 years of age attending routine HIV clinic visits was screened for hypertension, diabetes, hyperlipidemia and tobacco smoking. We observed HIV visits with and without screening and measured time spent on HIV and CVD risk factor screening activities. We compared screened and unscreened patients on total visit time and time spent receiving HIV services using Wilcoxon rank‐sum tests. A separate convenience sample of screened patients participated in exit interviews to assess their satisfaction with screening.

Results

We observed 172 patient visits (122 with CVD risk factor screening and 50 without). Screening increased total visit time from a median (range) of 4 minutes (2 to 11) to 15 minutes (9 to 30) (< 0.01). Time spent on HIV care was not affected: 4 (2 to 10) versus 4 (2 to 11) (= 0.57). We recruited 126 patients for exit interviews, all of whom indicated that they would recommend screening to others.

Conclusion

Provision of CVD risk factor screening more than tripled the length of routine HIV clinic visits but did not reduce the time spent on HIV services. Programme managers need to take longer visit duration into account in order to effectively integrate CVD risk factor screening and counselling into HIV programmes.
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8.

Introduction

Population‐level improvements in knowledge about HIV may reduce the stigma attached to HIV and ensure maximal uptake of HIV prevention initiatives. The extent to which levels of HIV knowledge in the general population of sub‐Saharan Africa have changed in the current era of antiretroviral therapy (ART) scale‐up remains unknown.

Methods

Data on HIV knowledge in the general population were drawn from the 2003 to 2015 Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) of 33 countries in sub‐Saharan Africa. The DHS/AIS contain five questions on HIV prevention and transmission that have been used by the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a core indicator of HIV knowledge. We created a composite HIV knowledge variable equal to the number of correct responses to these five questions; a participant was considered to have comprehensive knowledge of HIV (yes/no) if he/she answered all five questions correctly. We fitted negative binomial regression models with cluster‐correlated robust standard errors and country fixed effects, adjusted for socio‐demographic variables, specifying HIV knowledge as the dependent variable and year as the explanatory variable. As an alternative parameterization, we also fitted a multivariable linear probability model with cluster‐correlated robust standard errors and country fixed effects specifying comprehensive knowledge of HIV as the dependent variable.

Results

A total of 791,186 women and 395,891 men participating in 75 DHS/AIS were included in the analyses. The mean HIV knowledge score was 3.7 among women and 3.9 among men (p < 0.001). Only 35% of women and 41% of men (p < 0.001) had a comprehensive knowledge of HIV. We estimated a modest but statistically significant positive association between year of DHS/AIS and HIV knowledge (adjusted b = 0.005; 95% confidence interval (CI), 0.001 to 0.009). Similarly, we estimated a statistically significant positive association between year of DHS/AIS and comprehensive knowledge of HIV (adjusted b = 0.011; 95% CI, 0.005 to 0.017), suggesting an approximately 1% relative increase per year in the percentage of the general population who possess a comprehensive knowledge of HIV.

Conclusions

There have been minimal improvements over time in HIV knowledge across sub‐Saharan Africa.
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9.

Introduction

Weaknesses in care programmes providing anti‐retroviral therapy (ART) persist and are often instigated by late HIV diagnosis and poor linkage to care. We investigated the potential for a home‐based counselling and testing (HBCT) campaign to be improved through the optimal timing and enhancement of testing rounds to generate greater health outcomes at minimum cost.

Methods

Using a mathematical model of HIV care calibrated to longitudinal data from The Academic Model Providing Access To Healthcare (AMPATH) in Kenya, we simulated HBCT campaigns between 2016 and 2036, assessing the impact and total cost of care for each, for a further 20 years.

Results

We find that simulating five equally spaced rounds averts 1.53 million disability‐adjusted life‐years (DALYs) at a cost of $1617 million. By altering the timing of HBCT rounds, a four‐round campaign can produce greater impact for lower cost. With “front‐loaded” rounds, the cost per DALY averted is reduced by 12% as fewer rounds are required ($937 vs. $1060). Furthermore, improvements to HBCT coverage and linkage to care avert over two million DALYs at a cost per DALY averted of $621 (41% less than the reference scenario).

Conclusions

Countries implementing HBCT can reduce costs by optimally timing rounds and generate greater health outcomes through improving linkage, coverage, and retention. Tailoring HBCT campaigns to individual settings can enhance patient outcomes for minimal cost.
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10.
11.

Design

Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV‐infected (universal test and treat, UTT) is now a global health standard. However, its population‐level impact, feasibility and cost remain unknown. Five community‐based trials have been implemented in sub‐Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials.

Methods

We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations.

Results

All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation.

Conclusions

We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence‐based decision making for HIV care in country and internationally.
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12.

Introduction

Emerging HIV epidemics have been documented among people who inject drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the HIV incidence among PWID due to sharing needles/syringes in MENA. It also delineates injecting drug use role as a driver of the epidemic in the population, and estimates impact of interventions.

Methods

A mathematical model of HIV transmission among PWID was applied in seven MENA countries with sufficient and recent epidemiological data and HIV prevalence ≥1% among PWID. Estimations of incident and/or prevalent infections among PWID, ex‐PWID and sexual partners of infected current and ex‐PWID were conducted.

Results

The estimated HIV incidence rate for 2017 among PWID ranged between 0.7% per person‐year (ppy) in Tunisia and 7.8% ppy in Pakistan, with Libya being an outlier (24.8% ppy). The estimated number of annual new infections was lowest in Tunisia (n = 79) and Morocco (n = 99), and highest in Iran and Pakistan (approximately n = 6700 each). In addition, 20 to 2208 and 5 to 837 new annual infections were estimated across the different countries among sexual partners of PWID and ex‐PWID respectively. Since epidemic emergence, the number of total ever acquired incident infections across countries was 706 to 90,015 among PWID, 99 to 18,244 among sexual partners of PWID, and 16 to 4360 among sexual partners of ex‐PWID. The estimated number of prevalent infections across countries was 341 to 23,279 among PWID, 119 to 16,540 among ex‐PWID, 67 to 10,752 among sexual partners of PWID, and 12 to 2863 among sexual partners of ex‐PWID. Increasing antiretroviral therapy (ART) coverage to the global target of 81% – factoring in ART adherence and current coverage – would avert about half of new infections among PWID and their sexual partners. Combining ART with harm reduction could avert over 90% and 70% of new infections among PWID and their sexual partners respectively.

Conclusions

There is considerable HIV incidence among PWID in MENA. Of all new infections ultimately due to injecting drug use, about 75% are among PWID and the rest among sexual partners. Of all prevalent infections ultimately attributed to injecting drug use as epidemic driver, about half are among PWID, 30% among ex‐PWID and 20% among sexual partners of PWID and ex‐PWID. These findings call for scale‐up of services for PWID, including harm reduction as well as testing and treatment services.
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13.

Introduction

There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.

Methods

The Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.

Results

Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (< 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.

Conclusions

We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.
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14.

Introduction

Community mobilization (CM) is increasingly recognized as critical to generating changes in social norms and behaviours needed to achieve reductions in HIV. We conducted a CM intervention to modify negative gender norms, particularly among men, in order to reduce associated HIV risk.

Methods

Twenty two villages in the Agincourt Health and Socio‐Demographic Surveillance Site in rural Mpumalanga, South Africa were randomized to either a theory‐based, gender transformative, CM intervention or no intervention. Two cross‐sectional, population‐based surveys were conducted in 2012 (pre‐intervention, n = 600 women; n = 581 men) and 2014 (post‐intervention, n = 600 women; n = 575 men) among adults ages 18 to 35 years. We used an intent‐to‐treat (ITT) approach using survey regression cluster‐adjusted standard errors to determine the intervention effect by trial arm on gender norms, measured using the Gender Equitable Mens Scale (GEMS), and secondary behavioural outcomes.

Results

Among men, there was a significant 2.7 point increase (Beta Coefficient 95% CI: 0.62, 4.78, p = 0.01) in GEMS between those in intervention compared to control communities. We did not observe a significant difference in GEMS scores for women by trial arm. Among men and women in intervention communities, we did not observe significant differences in perpetration of intimate partner violence (IPV), condom use at last sex or hazardous drinking compared to control communities. The number of sex partners in the past 12 months (AOR 0.29, 95% CI 0.11 to 0.77) were significantly lower in women in intervention communities compared to control communities and IPV victimization was lower among women in intervention communities, but the reduction was not statistically significant (AOR 0.53, 95% CI 0.24 to 1.16).

Conclusion

Community mobilization can reduce negative gender norms among men and has the potential to create environments that are more supportive of preventing IPV and reducing HIV risk behaviour. Nevertheless, we did not observe that changes in attitudes towards gender norms resulted in desired changes in risk behaviours suggesting that more time may be necessary to change behaviour or that the intervention may need to address behaviours more directly.

Clinical Trials number

ClinicalTrials.gov NCT02129530.
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15.

Introduction

HIV testing has rapidly expanded into diverse, decentralized settings. While increasing accessibility to HIV testing is beneficial, it may lead to unintended consequences such as being pressured to test. We examined the frequency, correlates and contexts of pressured HIV testing among Chinese men who have sex with men (MSM) using mixed methods.

Methods

We conducted an online survey of MSM (N = 1044) in May 2017. Pressured HIV testing was defined as being forced to test for HIV. We conducted logistic regression analysis to determine the associations between pressured HIV testing and socio‐demographic and sexual behavioural factors. Follow‐up interviews (n = 17) were conducted with men who reported pressured testing and we analysed qualitative data using a thematic analysis approach.

Results

Ninety‐six men (9.2%) reported experiencing pressure to test for HIV. Regular male sex partners were the most common source of pressure (61%, 59/96), and the most common form of pressure was a threat to end a relationship with the one who was being pressured (39%, 37/96). We found a higher risk of pressured testing in men who had only used HIV self‐testing compared to men who had never self‐tested (AOR 2.39 (95%CI: 1.38 to 4.14)). However, this relationship was only significant among men with low education (AOR 5.88 (95% CI: 1.92 to 17.99)) and not among men with high education (AOR 1.62 (95% CI: 0.85 to 3.10)). After pressured testing, about half of men subsequently tested for HIV (55%, 53/96) without pressure – none reported being diagnosed with HIV. Consistent with this finding, qualitative data suggest that perceptions of pressure existed on a continuum and depended on the relationship status of the one who pressured them. Although being pressured to test was accompanied by negative feelings, men who were pressured into testing often changed their attitude towards HIV testing, testing behaviours, sexual behaviours and relationship with the one who pressured them to test.

Conclusion

Pressured HIV testing was reported among Chinese MSM, especially from men with low education levels and men who received HIV self‐testing. However, in some circumstances, pressure to test helped MSM in several ways, challenging our understanding of the role of agency in the setting of HIV testing.
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16.

Introduction

Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.

Methods

We performed meta‐analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random‐effect models. I2 statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.

Results and Discussion

In review 1, 37 publications (25 independent studies) were included in the meta‐analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high‐risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta‐analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.

Conclusions

These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.
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17.

Introduction

Integration of services to screen and manage mental health and substance use disorders (MSDs) into HIV care settings has been identified as a promising strategy to improve mental health and HIV treatment outcomes among people living with HIV/AIDS (PLWHA) in low‐ and middle‐income countries (LMICs). Data on the extent to which HIV treatment sites in LMICs screen and manage MSDs are limited. The objective of this study was to assess practices for screening and treatment of MSDs at HIV clinics in LMICs participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

Methods

We surveyed a stratified random sample of 95 HIV clinics in 29 LMICs in the Caribbean, Central and South America, Asia‐Pacific and sub‐Saharan Africa. The survey captured information onsite characteristics and screening and treatment practices for depression, post‐traumatic stress disorder (PTSD), substance use disorders (SUDs) and other mental health disorders.

Results

Most sites (n = 76, 80%) were in urban areas. Mental health screening varied by disorder: 57% of sites surveyed screened for depression, 19% for PTSD, 55% for SUDs and 29% for other mental health disorders. Depression, PTSD, SUDs and other mental health disorders were reported as managed on site (having services provided at the HIV clinic or same health facility) at 70%, 51%, 41% and 47% of sites respectively. Combined availability of screening and on‐site management of depression, PTSD, and SUDs, and other mental health disorders was reported by 42%, 14%, 26% and 19% of sites, respectively. On‐site management of depression and PTSD was reported significantly less often in rural as compared to urban settings (depression: 33% and 78% respectively; PTSD: 24% and 58% respectively). Screening for depression and SUDs was least commonly reported by HIV programmes that treated only children as compared to HIV programmes that treated only adults or treated both adults and children.

Conclusions

Significant gaps exist in the management of MSDs in HIV care settings in LMICs, particularly in rural settings. Identification and evaluation of optimal implementation strategies to scale and sustain integrated MSDs and HIV care is needed.
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18.

Introduction

Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre‐exposure prophylaxis (PrEP) programme in these populations.

Methods

We used the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age‐stratified annual HIV incidence (age ≤ 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil‐based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness‐to‐pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015: $8540 USD).

Results

Lifetime HIV infection risk among high‐risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per‐person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV‐related medical costs from $4100 to $8420, which led to an incremental cost‐effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost‐effective (<1x GDP) under plausible variation in key parameters, including PrEP effectiveness and cost, initial cohort age and HIV testing frequency on/off PrEP.

Conclusion

Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost‐effective.
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19.

Introduction

Combined anti‐retroviral therapy (cART) transformed HIV‐1 from a deadly disease into a chronic infection, but does not cure HIV infection. It also does not fully restore HIV‐induced gut damage unless administered extremely early after infection. Additional biomarkers are needed to evaluate the capacity of therapies aimed at HIV remission/cure to restore HIV‐induced intestinal immune damage and limit chronic inflammation. Herein, we aimed to identify a systemic surrogate marker whose levels would reflect gut immune damage such as intestinal Th17 cell loss starting from primary HIV‐1 infection.

Methods

Biomarker discovery approaches were performed in four independent cohorts, covering HIV‐1 primary and chronic infection in 496 naïve or cART‐treated patients (Amsterdam cohort (ACS), ANRS PRIMO, COPANA and CODEX cohorts). The concentration and activity of soluble Dipeptidylpeptidase 4 (sDPP4) were quantified in the blood from these patients, including pre‐ and post‐infection samples in the ACS cohort. For quantification of DPP4 in the gut, we utilized two non‐human primate models, representing pathogenic (macaque) and non‐pathogenic (African green monkey) SIV infection. Four gut compartments were analysed in each animal model (ileum, jejunum, colon and rectum) for quantification of DPP4, RORC and TBX21 gene expression in sorted CD4+ cells. To analyse if sDPP4 levels increase when Th17 cells were restored, we quantified sDPP4 in plasma from SIV‐infected macaques treated with IL‐21.

Results

We showed that sDPP4 levels were strongly decreased in primary HIV‐1 infection. Strikingly, sDPP4 levels in primary HIV‐1 infection predicted time to AIDS. They were not increased by cART in chronic HIV‐1 infection (median 36 months on cART). In the gut of SIV‐infected non‐human primates, DPP4 mRNA was higher in CD4+ than CD4 leucocytes. DPP4 specifically correlated with RORC expression, a Th17 marker, in CD4+ cells from the intestine. We further demonstrated that sDPP4 activity levels were increased in animals treated with IL‐21 and that this increase was associated with restoration of the Th17 compartment and reduced inflammation. Furthermore, DPP4 mRNA levels in small intestine CD4+ cells positively correlated with circulating DPP4 activity.

Conclusion

These data provide evidence that blood sDPP4 levels could be useful as a correlate for HIV‐induced intestinal damage.
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20.

Introduction

Modelling suggests that early diagnosis and immediate antiretroviral therapy (ART) among key populations would have a substantial impact in reducing HIV transmission and mortality in Vietnam. An implementation research project of “test‐and‐treat” among people who inject drugs (PWID) was developed to inform effective roll‐out of such interventions.

Methods

“Test‐and‐treat” was offered to PWID in two high burden provinces, Thai Nguyen and Thanh Hoa. The interventions comprised the offer of biannual HIV testing and immediate ART, irrespective of CD4 count. PWID were enrolled between April 2014 and July 2015 and followed up for 12 months, and retention, HIV viral load (VL) and risk behaviours were assessed. Retention in care of this prospective cohort was compared with the retention among men enrolled in care in the preceding period (April 2012 to March 2013) at the same clinics when ART was initiated at CD4 cell count ≤350 cells/mm3.

Results

In total, 287 HIV positive PWID started immediate ART. The majority (98%) were men; median age was 34; and median (interquartile range) CD4 count was 199 (50 to 402) cells/mm3. After 12 months, 238 participants (83%) were retained on ART, and 205 achieved viral suppression (<1000 copies/mL) (92% among those in whom VL was measured, 71% overall). Baseline CD4 count ≤100 cells/mm3 and history of imprisonment were associated with lower retention and viral suppression, while engagement in methadone maintenance was associated with higher retention. Retention in care was higher in the “test‐and‐treat” cohort (83%) compared with men enrolled in care in the preceding period (78%), primarily because lost‐to‐follow‐up during pre‐ART care was eliminated. No decline in consistent condom use and clean needle use was observed.

Conclusions

Early ART initiation resulted in successful treatment outcomes among PWID, with no observed increase in self‐reported risk behaviours, suggesting feasibility and potential effectiveness of “test‐and‐treat” approach. The results also call for differentiated care for PWID, including promoting early diagnosis and engagement in methadone maintenance therapy while enhancing care for those with advanced HIV disease and history of imprisonment.
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