HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women.

Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

Socioeconomic Burdens of the COVID-19 Pandemic on LMIC Populations with Increased HIV Vulnerabilities.

PURPOSE OF REVIEW: To review the impact of the COVID-19 pandemic and its public health response on key populations at risk of HIV infection, with a focus on sex workers. RECENT FINDINGS: Since last year several groups have documented how the COVID-19 pandemic has impacted the livelihoods and health of sex workers. We focus on case studies from Kenya, Ukraine, and India and place these in the broader global context of sex worker communities, drawing on common themes that span geographies. COVID-19-associated lockdowns have significantly disrupted sex work, leading to economic and health challenges for sex workers, ranging from HIV-related services to mental health and exposure to violence. Several adaptations have been undertaken by sex workers and frontline workers, including migration, a move to mobile services, and struggling to find economic supports. Strengthening community-based responses for future pandemics and other shocks is critical to safeguard the health of marginalized populations.

Beyond remedicalisation: a community-led PrEP demonstration project among sex workers in India.

Global health policy-makers have called for demonstration projects to better understand pre-exposure prophylaxis' (PrEP) effectiveness across geographies and populations. Ashodaya, a sex worker collective, initiated a PrEP project in Mysore, India. We conducted a project ethnography to explore the role that community participation played within the project. Although the project proved immensely successful in terms of retention and adherence, to explain these findings we point towards Ashodaya's history of collectivisation around sexual health-a history of community action that has given rise to new spaces of belonging and accumulated knowledges that became instrumental in the formulation of strategies to confront anticipated challenges during the project. These strategies included: (1) the participation of community leaders as the first participants to take PrEP, followed by the sharing of their experiences through testimonials to their peers; (2) the endorsement of PrEP among community leaders living with HIV, to avoid social divisions around HIV status; and (3) ongoing community-level support from outreach workers that went beyond administering PrEP to address the various needs of the community. These community-led approaches demonstrate that communities hold key insights into the delivery of clinically-oriented interventions, suggesting the vital role they continue to play in planning and implementing new prevention technologies.

A rapid review of pre-exposure prophylaxis for HIV in the Asia-Pacific region: recommendations for scale up and future directions.

Decline in new HIV infections in the Asia-Pacific region (APAC) continues to be slow, emphasising the importance of scaling up new HIV prevention strategies, such as pre-exposure prophylaxis (PrEP). To help inform PrEP rollout in APAC, we conducted a rapid review of published literature on PubMed from 2015 to 2020, to assess feasibility, implementation strategies, cost-effectiveness, and availability of national policies and guidelines; for the latter, we also did an expanded Internet search. This review focussed on nine countries contributing >95% of new infections in this region. A total of 36 PrEP-related studies conducted among men who have sex with men, female sex workers, and transgender women were included, of which 29 were quantitative, six were qualitative and one was a mixed-method study. Most of the studies have addressed the availability and acceptability of PrEP, whereas cost-effectiveness of any approach was assessed by limited studies. Limited published information was available about national PrEP policies and guidelines; of the selected nine countries, five have adopted the recommended World Health Organization PrEP policy of which four have integrated it in their national HIV response. HIV risk perception concerns about safety, side-effects, stigma, and affordability were major challenges to PrEP acceptance. Community-based implementation has the potential to address these. Limited evidence suggested merging PrEP implementation with ongoing targeted intervention and treatment programs could be a cost-effective approach. To stem the epidemic, newer effective prevention strategies, like PrEP, should be urgently adopted within the context of combination HIV prevention approaches.

Pragmatic women: negotiating sex work, pregnancy, and parenting in Mysore, South India.

Persisting inequities in maternal health pose a particular burden for marginalised populations such as sex workers. However, current literature on pregnancy and sex work is limited to mostly quantitative studies focusing on contraception use, unplanned and/or undesired pregnancies and unsafe abortions. Additionally, emphasis has been placed on the prevention, treatment and care of STIs and HIV with less attention accorded to women's pregnancy desires and implications to work. In this paper, we explore sex workers' conflicted experiences surrounding pregnancy, parenthood, and work. Forty-six women participated in in-depth interviews as part of a qualitative exploratory study conducted in close collaboration with a sex worker collective in the city of Mysore (South India). Our analysis focuses on women's pragmatic responses to pregnancy desires, workplace challenges during and after pregnancy, strategies for managing risk and approaches to managing work and childcare. We show that women confront various intersecting challenges with respect to pregnancy and sex work. Women's complex decision-making balances multiple considerations while highlighting the temporal dimension of pragmatism as women respond not only to the immediacy of an encounter but also in anticipation of a better future.

Sex Worker Community-led Interventions Interrupt Sexually Transmitted Infection/Human Immunodeficiency Virus Transmission and Improve Human Immunodeficiency Virus Cascade Outcomes: A Program Review from South India.

Ashodaya Samithi, an organization run by and for female, male, and transgender sex workers in Mysore, India, has worked since 2004 to prevent sexually transmitted infection (STI)/human immunodeficiency virus (HIV) transmission and improve HIV cascade outcomes. We reviewed published and programmatic data, including measures of coverage, uptake, utilization and retention, and relate STI/HIV outcomes to evolving phases of community mobilization. Early interventions designed "for" sex workers mapped areas of sex work and reached half the sex workers in Mysore with condoms and STI services. By late 2005, when Ashodaya Samithi registered as a community-based organization, interventions were implemented "with" sex workers as active partners. Microplanning was introduced to enable peer educators to better organize and monitor their outreach work to reach full coverage. By 2008, programs were run "by" sex workers, with active community decision making. Program data show complete coverage of community outreach and greater than 90% clinic attendance for quarterly checkups by 2010. Reported condom use with last occasional client increased from 65% to 90%. Surveys documented halving of HIV and syphilis prevalence between 2004 and 2009, while gonorrhoea declined by 80%. Between 2005 and 2013, clinic checkups tripled, whereas the number of STIs requiring treatment declined by 99%. New HIV infections also declined, and Ashodaya achieved strong cascade outcomes for HIV testing, antiretroviral treatment linkage, and retention. Program performance dropped markedly during several periods of interrupted funding, then rebounded when restored. Ashodaya appear to have achieved rapid STI/HIV control with community-led approaches including microplanning. Available data support near elimination of curable STIs and optimal cascade outcomes.

Sexual and reproductive health services utilization by female sex workers is context-specific: results from a cross-sectional survey in India, Kenya, Mozambique and South Africa.

BACKGROUND: Female sex workers (FSWs) are extremely vulnerable to adverse sexual and reproductive health (SRH) outcomes. To mitigate these risks, they require access to services covering not only HIV prevention but also contraception, cervical cancer screening and sexual violence. To develop context-specific intervention packages to improve uptake, we identified gaps in service utilization in four different cities. METHODS: A cross-sectional survey was conducted, as part of the baseline assessment of an implementation research project. FWSs were recruited in Durban, South Africa (n = 400), Mombasa, Kenya (n = 400), Mysore, India (n = 458) and Tete, Mozambique (n = 308), using respondent-driven sampling (RDS) and starting with 8-16 'seeds' identified by the peer educators. FSWs responded to a standardised interviewer-administered questionnaire about the use of contraceptive methods and services for cervical cancer screening, sexual violence and unwanted pregnancies. RDS-adjusted proportions and surrounding 95% confidence intervals were estimated by non-parametric bootstrapping, and compared across cities using post-hoc pairwise comparison tests with Dunn-Sidák correction. RESULTS: Current use of any modern contraception ranged from 86.2% in Tete to 98.4% in Mombasa (p = 0.001), while non-barrier contraception (hormonal, IUD or sterilisation) varied from 33.4% in Durban to 85.1% in Mysore (p < 0.001). Ever having used emergency contraception ranged from 2.4% in Mysore to 38.1% in Mombasa (p < 0.001), ever having been screened for cervical cancer from 0.0% in Tete to 29.0% in Durban (p < 0.001), and having gone to a health facility for a termination of an unwanted pregnancy from 15.0% in Durban to 93.7% in Mysore (p < 0.001). Having sought medical care after forced sex varied from 34.4% in Mombasa to 51.9% in Mysore (p = 0.860). Many of the differences between cities remained statistically significant after adjusting for variations in FSWs' sociodemographic characteristics. CONCLUSION: The use of SRH commodities and services by FSWs is often low and is highly context-specific. Reasons for variation across cities need to be further explored. The differences are unlikely caused by differences in socio-demographic characteristics and more probably stem from differences in the availability and accessibility of SRH services. Intervention packages to improve use of contraceptives and SRH services should be tailored to the particular gaps in each city.

A community empowerment approach to the HIV response among sex workers: effectiveness, challenges, and considerations for implementation and scale-up.

A community empowerment-based response to HIV is a process by which sex workers take collective ownership of programmes to achieve the most effective HIV outcomes and address social and structural barriers to their overall health and human rights. Community empowerment has increasingly gained recognition as a key approach for addressing HIV in sex workers, with its focus on addressing the broad context within which the heightened risk for infection takes places in these individuals. However, large-scale implementation of community empowerment-based approaches has been scarce. We undertook a comprehensive review of community empowerment approaches for addressing HIV in sex workers. Within this effort, we did a systematic review and meta-analysis of the effectiveness of community empowerment in sex workers in low-income and middle-income countries. We found that community empowerment-based approaches to addressing HIV among sex workers were significantly associated with reductions in HIV and other sexually transmitted infections, and with increases in consistent condom use with all clients. Despite the promise of a community-empowerment approach, we identified formidable structural barriers to implementation and scale-up at various levels. These barriers include regressive international discourses and funding constraints; national laws criminalising sex work; and intersecting social stigmas, discrimination, and violence. The evidence base for community empowerment in sex workers needs to be strengthened and diversified, including its role in aiding access to, and uptake of, combination interventions for HIV prevention. Furthermore, social and political change are needed regarding the recognition of sex work as work, both globally and locally, to encourage increased support for community empowerment responses to HIV.

Global epidemiology of HIV among female sex workers: influence of structural determinants.

Female sex workers (FSWs) bear a disproportionately large burden of HIV infection worldwide. Despite decades of research and programme activity, the epidemiology of HIV and the role that structural determinants have in mitigating or potentiating HIV epidemics and access to care for FSWs is poorly understood. We reviewed available published data for HIV prevalence and incidence, condom use, and structural determinants among this group. Only 87 (43%) of 204 unique studies reviewed explicitly examined structural determinants of HIV. Most studies were from Asia, with few from areas with a heavy burden of HIV such as sub-Saharan Africa, Russia, and eastern Europe. To further explore the potential effect of structural determinants on the course of epidemics, we used a deterministic transmission model to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs. This modelling suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty interval [UI] 1-31) and 20% in Canada (95% UI 3-39) through its immediate and sustained effect on non-condom use) among FSWs and their clients in the next decade. In Kenya, scaling up of access to antiretroviral therapy among FSWs and their clients to meet WHO eligibility of a CD4 cell count of less than 500 cells per µL could avert 34% (95% UI 25-42) of infections and even modest coverage of sex worker-led outreach could avert 20% (95% UI 8-36) of infections in the next decade. Decriminalisation of sex work would have the greatest effect on the course of HIV epidemics across all settings, averting 33-46% of HIV infections in the next decade. Multipronged structural and community-led interventions are crucial to increase access to prevention and treatment and to promote human rights for FSWs worldwide.

HIV prevention and care-seeking behaviour among female sex workers in four cities in India, Kenya, Mozambique and South Africa.

OBJECTIVE: To identify gaps in the use of HIV prevention and care services and commodities for female sex workers, we conducted a baseline cross-sectional survey in four cities, in the context of an implementation research project aiming to improve use of sexual and reproductive health services. METHODS: Using respondent-driven sampling, 400 sex workers were recruited in Durban, 308 in Tete, 400 in Mombasa and 458 in Mysore and interviewed face-to-face. RDS-adjusted proportions were estimated by nonparametric bootstrapping and compared across cities using post hoc pairwise comparison. RESULTS: Condom use with last client ranged from 88.3% to 96.8%, ever female condom use from 1.6% to 37.9%, HIV testing within the past 6 months from 40.5% to 70.9%, receiving HIV treatment and care from 35.5% to 92.7%, care seeking for last STI from 74.4% to 87.6% and having had at least 10 contacts with a peer educator in the past year from 5.7% to 98.1%. Many of the differences between cities remained statistically significant (P < 0.05) after adjusting for differences in FSWs' socio-demographic characteristics. CONCLUSION: The use of HIV prevention and care by FSWs is often insufficient and differed greatly between cities. Differences could not be explained by variations in socio-demographic sex worker characteristics. Models to improve use of condoms and HIV prevention and care services should be tailored to the specific context of each site. Programmes at each site must focus on improving availability and uptake of those services that are currently least used.

Inequity in costs of seeking sexual and reproductive health services in India and Kenya.

OBJECTIVE: This study aims to assess inequity in expenditure on sexual and reproductive health (SRH) services in India and Kenya. In addition, this analysis aims to measure the extent to which payments are catastrophic and to explore coping mechanisms used to finance health spending. METHODS: Data for this study were collected as a part of the situational analysis for the "Diagonal Interventions to Fast Forward Enhanced Reproductive Health" (DIFFER) project, a multi-country project with fieldwork sites in three African sites; Mombasa (Kenya), Durban (South Africa) and Tete (Mozambique), and Mysore in India. Information on access to SRH services, the direct costs of seeking care and a range of socio-economic variables were obtained through structured exit interviews with female SRH service users in Mysore (India) and Mombasa (Kenya) (n = 250). The costs of seeking care were analysed by household income quintile (as a measure of socio-economic status). The Kakwani index and quintile ratios are used as measures of inequitable spending. Catastrophic spending on SRH services was calculated using the threshold of 10% of total household income. RESULTS: The results showed that spending on SRH services was highly regressive in both sites, with lower income households spending a higher percentage of their income on seeking care, compared to households with a higher income. Spending on SRH as a percentage of household income ranged from 0.02 to 6.2% and 0.03-7.5% in India and Kenya, respectively. There was a statistically significant difference in the proportion of spending on SRH services across income quintiles in both settings. In India, the poorest households spent two times, and in Kenya ten times, more on seeking care than the least poor households. The most common coping mechanisms in India and Kenya were "receiving [money] from partner or household members" (69%) and "using own savings or regular income" (44%), respectively. CONCLUSION: Highly regressive spending on SRH services highlights the heavier burden borne by the poorest when seeking care in resource-constrained settings such as India and Kenya. The large proportion of service users, particularly in India, relying on money received from family members to finance care seeking suggests that access would be more difficult for those with weak social ties, small social networks or weak bargaining positions within the family - although this requires further study.

Community empowerment and involvement of female sex workers in targeted sexual and reproductive health interventions in Africa: a systematic review.

BACKGROUND: Female sex workers (FSWs) experience high levels of sexual and reproductive health (SRH) morbidity, violence and discrimination. Successful SRH interventions for FSWs in India and elsewhere have long prioritised community mobilisation and structural interventions, yet little is known about similar approaches in African settings. We systematically reviewed community empowerment processes within FSW SRH projects in Africa, and assessed them using a framework developed by Ashodaya, an Indian sex worker organisation. METHODS: In November 2012 we searched Medline and Web of Science for studies of FSW health services in Africa, and consulted experts and websites of international organisations. Titles and abstracts were screened to identify studies describing relevant services, using a broad definition of empowerment. Data were extracted on service-delivery models and degree of FSW involvement, and analysed with reference to a four-stage framework developed by Ashodaya. This conceptualises community empowerment as progressing from (1) initial engagement with the sex worker community, to (2) community involvement in targeted activities, to (3) ownership, and finally, (4) sustainability of action beyond the community. RESULTS: Of 5413 articles screened, 129 were included, describing 42 projects. Targeted services in FSW 'hotspots' were generally isolated and limited in coverage and scope, mostly offering only free condoms and STI treatment. Many services were provided as part of research activities and offered via a clinic with associated community outreach. Empowerment processes were usually limited to peer-education (stage 2 of framework). Community mobilisation as an activity in its own right was rarely documented and while most projects successfully engaged communities, few progressed to involvement, community ownership or sustainability. Only a few interventions had evolved to facilitate collective action through formal democratic structures (stage 3). These reported improved sexual negotiating power and community solidarity, and positive behavioural and clinical outcomes. Sustainability of many projects was weakened by disunity within transient communities, variable commitment of programmers, low human resource capacity and general resource limitations. CONCLUSIONS: Most FSW SRH projects in Africa implemented participatory processes consistent with only the earliest stages of community empowerment, although isolated projects demonstrate proof of concept for successful empowerment interventions in African settings.

Combating human trafficking in the sex trade: can sex workers do it better?

BACKGROUND: The dominant anti-trafficking paradigm conflates trafficking and sex work, denying evidence that most sex workers choose their profession and justifying police actions that disrupt communities, drive sex workers underground and increase vulnerability. METHODS: We review an alternative response to combating human trafficking and child prostitution in the sex trade, the self-regulatory board (SRB) developed by Durbar Mahila Samanwaya Committee (DMSC, Sonagachi). RESULTS: DMSC-led interventions to remove minors and unwilling women from sex work account for over 80% of successful 'rescues' reported in West Bengal. From 2009 through 2011, 2195 women and girls were screened by SRBs: 170 (7.7%) minors and 45 (2.1%) unwilling adult women were assisted and followed up. The remaining 90.2% received counselling, health care and the option to join savings schemes and other community programmes designed to reduce sex worker vulnerability. Between 1992 and 2011 the proportion of minors in sex work in Sonagachi declined from 25 to 2%. CONCLUSIONS: With its universal surveillance of sex workers entering the profession, attention to rapid and confidential intervention and case management, and primary prevention of trafficking-including microcredit and educational programmes for children of sex workers-the SRB approach stands as a new model of success in anti-trafficking work.

Beyond internalised stigma: daily moralities and subjectivity among self-identified kothis in Karnataka, South India.

The Bill and Melinda Gates Foundation has poured a tremendous amount of resources into epidemic prevention in India's high HIV prevalence zones, through their Avahan initiative. These community-centred programmes operate under the assumption that fostering community-based organisational development and empowering the community to take charge of HIV prevention and education will help to transform the wider social inequalities that inhibit access to health services. Focusing on the South Indian state of Karnataka, this paper explores a troubling set of local narratives that, we contend, hold broader implications for future programme planning and implementation. Although confronting stigma and discrimination has become a hallmark in community mobilisation discourse, communities of self-identified kothis (feminine men) who were involved in Avahan programme activities continued to articulate highly negative attitudes about their own sexualities in relation to various spheres of social life. Rather than framing an understanding of these narratives in psychological terms of 'internalized stigma', we draw upon medical anthropological approaches to the study of stigma that emphasise how social, cultural and moral processes create stigmatising conditions in the everyday lives of people. The way stigma continues to manifest itself in the self-perceptions of participants points to an area that warrants critical public health attention.

Sex worker-led structural interventions in India: a case study on addressing violence in HIV prevention through the Ashodaya Samithi collective in Mysore.

BACKGROUND & OBJECTIVES: Structural interventions have the capacity to improve the outcomes of HIV/AIDS interventions by changing the social, economic, political or environmental factors that determine risk and vulnerability. Marginalized groups face disproportionate barriers to health, and sex workers are among those at highest risk of HIV in India. Evidence in India and globally has shown that sex workers face violence in many forms ranging from verbal, psychological and emotional abuse to economic extortion, physical and sexual violence and this is directly linked to lower levels of condom use and higher levels of sexually transmitted infections (STIs), the most critical determinants of HIV risk. We present here a case study of an intervention that mobilized sex workers to lead an HIV prevention response that addresses violence in their daily lives. METHODS: This study draws on ethnographic research and project monitoring data from a community-led structural intervention in Mysore, India, implemented by Ashodaya Samithi. Qualitative and quantitative data were used to characterize baseline conditions, community responses and subsequent outcomes related to violence. RESULTS: In 2004, the incidence of reported violence by sex workers was extremely high (> 8 incidents per sex worker, per year) but decreased by 84 per cent over 5 years. Violence by police and anti-social elements, initially most common, decreased substantially after a safe space was established for sex workers to meet and crisis management and advocacy were initiated with different stakeholders. Violence by clients, decreased after working with lodge owners to improve safety. However, initial increases in intimate partner violence were reported, and may be explained by two factors: (i) increased willingness to report such incidents; and (ii) increased violence as a reaction to sex workers' growing empowerment. Trafficking was addressed through the establishment of a self-regulatory board (SRB). The community's progressive response to violence was enabled by advancing community mobilization, ensuring community ownership of the intervention, and shifting structural vulnerabilities, whereby sex workers increasingly engaged key actors in support of a more enabling environment. INTERPRETATION & CONCLUSIONS: Ashodaya's community-led response to violence at multiple levels proved highly synergistic and effective in reducing structural violence.

Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data.

BACKGROUND: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset. METHODS: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min. FINDINGS: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68-4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00-89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44-11·20) and less than 60 mL/min (aHR 20·83, 12·83-33·82). INTERPRETATION: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use. FUNDING: Unitaid, Bill & Melinda Gates Foundation, WHO.

Modelling the interactions between herpes simplex virus type 2 and HIV: implications for the HIV epidemic in southern India.

BACKGROUND: The role of herpes simplex virus type 2 (HSV-2) in the HIV epidemic and the potential impact of HSV-2 suppressive therapy have previously been explored only within the context of sub-Saharan Africa. In this analysis, modelling is used to estimate the contribution of HSV-2 to HIV transmission from clients to female sex workers (FSW) in a southern Indian setting and the maximum potential impact of 'perfect' HSV-2 suppressive therapy on HIV incidence. METHODS: A dynamic HSV-2/HIV model was developed, parameterised and fitted to Mysore data. The model estimated the attributable fractions of HIV infections due to HSV-2. Multivariate sensitivity analyses and regression analyses were conducted. RESULTS: The model suggests that 36% (95% CI 22% to 62%) of FSW HIV infections were due to HSV-2, mostly through HSV-2 asymptomatic shedding. Even if HSV-2 suppressive therapy could eliminate the effect of HSV-2 on HIV infectivity among all co-infected clients, only 15% (95% CI 3% to 41%) of HIV infections among FSW would have been averted. 36% (95% CI 18% to 61%) of HIV infections among HSV-2-infected FSW could have been averted if suppressive therapy reduced their risk of HIV acquisition to that of HSV-2-uninfected FSW. CONCLUSIONS: HSV-2 contributes substantially to HIV in this southern Indian context. However, even in the best case scenario, HSV-2 suppressive therapy is unlikely to reduce HIV transmission or acquisition by more than 50% (as aimed for in recent trials), because of the limited strength of the interaction effect between HSV-2 and HIV.

Confronting structural violence in sex work: lessons from a community-led HIV prevention project in Mysore, India.

Evidence from community-led HIV prevention projects suggests that structural interventions may result in reduced rates of HIV and STIs. The complex relationship between empowerment and confronting stigma, discrimination and physical abuse necessitates further investigation into the impact that such interventions have on the personal risks for sex workers. This article aims to describe lived experiences of members from a sex worker's collective in Mysore, India and how they have confronted structural violence. The narratives highlight experiences of violence and the development and implementation of strategies that have altered the social, physical, and emotional environment for sex workers. Building an enabling environment was key to reducing personal risks inherent to sex work, emphasizing the importance of community-led structural interventions for sex workers in India.

Prevalence of HIV and sexually transmitted infections among clients of female sex workers in Karnataka, India: a cross-sectional study.

BACKGROUND: Studies have demonstrated the significance of commercial sex work in the ongoing transmission of HIV and other sexually transmitted infections (STIs) in India. Clients of female sex workers (FSWs) are thought to be an important bridging population for HIV/STIs. However, there is a lack of information on basic characteristics of sex work clients. This study sought to describe the prevalence of HIV and other STIs, as well as examine the determinants of these pathogens among a sample of clients in south India. METHODS: Data were from a cross-sectional biological and behavioural survey of FSW clients from six districts in Karnataka State, India. The prevalence of HIV, syphilis, herpes simplex virus type 2 (HSV-2), chlamydia (CT) and gonorrhoea (NG) among clients was examined. Multivariable logistic regression models were used to analyse the socio-demographic, sexual behaviour and sex-work related characteristics related to the prevalence of each pathogen. Sampling weights and appropriate survey methods were utilized in regression models to account for complex sampling design. RESULTS: The total sample size was 2,745. The average age of clients was 30.4 (SE:0.3). Across the total sample, the prevalence of HIV, HSV-2, syphilis and CT/NG was 5.6%, 28.4%, 3.6% and 2.2%, respectively. The prevalence of HIV/STIs varied substantially across districts, reaching statistical significance for HIV (p<.0001) and CT/NG (p=.005). In multivariable models, duration of paying for commercial sex was associated with increased risk for HIV and HSV-2 (AOR: 1.1; 95%CI: 1.0-1.1, p<.0001). Clients with brothels as a main FSW solicitation site were associated with increased risk of HIV (AOR: 2.4; 95%CI: 1.2-4.7, p=.001), while those frequenting lodges were at increased risk for CT/NG (AOR: 6.3; 95%CI: 1.9-20.6, p=.03). Examining co-infections, clients with HSV-2 infections were at substantially higher risk of being HIV-positive (AOR: 10.4; 95%CI: 6.1-17.7, p<.0001). CONCLUSIONS: This study fills in important gaps in knowledge regarding clients in southern India. The strong association between HIV and HSV-2 infections highlights the complications in designing effective prevention, intervention and management programs of this well-hidden population.