Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study.

Background: HIV incidence estimation is critical for monitoring the HIV epidemic dynamics and the effectiveness of public health prevention interventions. We aimed to identify sexual and gender minorities (SGM) with recent HIV infections, factors associated with recent HIV infection, and to estimate annualised HIV incidence rates. Methods: Cross-sectional multicentre study in HIV testing services in Brazil and Peru (15 cities). Inclusion criteria: 18+ years, SGM assigned male at birth, not using pre-/post-exposure prophylaxis. We identified recent HIV infection using the Maxim HIV-1 LAg-Avidity EIA assay as part of a recent infection testing algorithm (RITA). Annualized HIV incidence was calculated using the UNAIDS/WHO incidence estimator tool. Multivariable logistic regression models were used to estimate factors associated with recent HIV infection. Trial registration: NCT05674682. Findings: From 31-Jan-2021 to 29-May-2022, 6899 individuals participated [Brazil: 4586 (66.5%); Peru: 2313 (33.5%)]; 5946 (86.2%) cisgender men, 751 (10.9%) transgender women and 202 (2.9%) non-binary/gender diverse. Median age was 27 (IQR: 23-34) years. HIV prevalence was 11.4% (N = 784/6899); 137 (2.0%) SGM were identified with recent HIV infection. The overall annualized HIV incidence rate was 3.88% (95% CI: 2.86-4.87); Brazil: 2.62% (95% CI: 1.78-3.43); Peru: 6.69% (95% CI: 4.62-8.69). Participants aged 18-24 years had higher odds of recent HIV infection compared to those aged 30+ years in both countries. Interpretation: Our results highlight the significant burden of HIV epidemic among SGM in large urban centres of Brazil and Peru. Public health policies and interventions to increase access to effective HIV prevention methods such as PrEP are urgently needed in Latin America. Funding: Unitaid, WHO (Switzerland), Ministry of Health from Brazil and Peru.

Preferences for PrEP modalities among gay, bisexual, and other men who have sex with men from Brazil, Mexico, and Peru: a cross-sectional study.

Background: Pre-exposure prophylaxis (PrEP) scale-up is urgent to reduce new HIV cases among gay, bisexual, and other men who have sex with men (MSM) in Latin America. Different PrEP modalities may increase PrEP uptake and adherence, especially among young MSM. Objectives: To assess preferences for PrEP modalities among MSM from Brazil, Mexico, and Peru. Design: Cross-sectional web-based study (March-May 2018) targeting MSM through advertisements on Grindr, Hornet, and Facebook. We included MSM aged ⩾ 18 years and who reported HIV-negative status. Methods: We assessed preferences for PrEP modalities with the following question: 'Considering that all following PrEP modalities were available, which one would you prefer considering a scale from 1 to 3 (1 = most preferred): daily oral PrEP, event-driven PrEP (ED-PrEP), and long-acting injectable PrEP'. We assessed factors associated with each most preferred PrEP modality per country using multivariable logistic regression models. Results: A total of 19,457 MSM completed the questionnaire (Brazil: 58%; Mexico: 31%; Peru: 11%); median age was 28 years [interquartile range (IQR): 24-34]. Overall, injectable PrEP was the most preferred modality [42%; 95% confidence interval (CI): 41-43], followed by daily PrEP (35%; 95% CI: 34-35), and ED-PrEP (23%; 95% CI: 23-24). In multivariable models, preferring injectable PrEP was associated with PrEP awareness in all three countries, while PrEP eligibility only in Brazil. Preferring daily PrEP was associated with younger age and lower income in Brazil and Mexico, and lower education only in Brazil. The odds of preferring ED-PrEP were lower among MSM aware and eligible for PrEP in Brazil and Mexico. Conclusions: Long-acting injectable PrEP was the preferred PrEP modality among MSM in Brazil, Mexico, and Peru, especially those aware and eligible for PrEP. Public health interventions to increase PrEP modalities literacy and availability in Latin America are urgent especially among MSM of young age, lower income, and lower education.

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Factors associated with long-term HIV pre-exposure prophylaxis engagement and adherence among transgender women in Brazil, Mexico and Peru: results from the ImPrEP study.

INTRODUCTION: The HIV epidemic continues to disproportionately impact Latin-American transgender women (TGW). We assessed factors associated with long-term pre-exposure prophylaxis (PrEP) engagement and adherence among TGW enrolled in the Implementation of PrEP (ImPrEP) study, the largest PrEP demonstration study in Latin America. METHODS: HIV-negative TGW aged ≥18 years reporting 1+eligibility criteria in the 6 months prior to enrolment (e.g. sex partner known to be living with HIV, condomless anal sex [CAS], transactional sex or having a sexually transmitted infection [STI]) who could safely take PrEP were enrolled. Follow-up visits were conducted at 4 weeks and then quarterly. We conducted logistic regression to identify factors associated with long-term PrEP engagement (3+ follow-up visits in 52 weeks) and complete self-reported adherence (no missed pills in the past 30 days) during follow-up. For both outcomes, we constructed multivariable models controlling for country, socio-demographics, sexual behaviour, substance use, STIs and self-reported adherence at 4 weeks (long-term engagement outcome only). RESULTS: From March 2018 to June 2021, ImPrEP screened 519 TGW, enrolled 494 (Brazil: 190, Mexico: 66 and Peru: 238) and followed them for 52 weeks. At baseline, 27.5% of TGW were aged 18-24 years, 67.8% were mixed-race and 31.6% had >secondary education. Most, 89.9% reported CAS, 61.9% had >10 sex partners and 71.9% reported transactional sex. HIV incidence was 1.82 cases per 100 person-years (95% confidence interval [CI]: 0.76-4.38). Almost half of TGW (48.6%) had long-term PrEP engagement, which was positively associated with reporting complete adherence at week 4 (aOR:2.94 [95%CI:1.88-4.63]) and was inversely associated with reporting CAS with unknown-HIV partner (aOR:0.52 [95%CI:0.34-0.81]), migration (aOR:0.54 [95%CI:0.34-0.84]), and being from Mexico (aOR:0.28 [95%CI:0.14-0.53]). Self-reported adherence was associated with TGW aged >34 (aOR:1.61 [95%CI:1.10-2.34]) compared to those aged 25-34 and those with >secondary education (aOR:1.55 [95%CI:1.10-2.19]) and was lower among TGW from Peru (aOR:0.29 [95%CI:0.21-0.41]) or reporting PrEP-related adverse effects (aOR:0.63 [95%CI:0.42-0.92]). CONCLUSIONS: Although TGW were willing to enrol in ImPrEP, long-term PrEP engagement and complete self-reported adherence were limited, and HIV incidence remained relatively high. A successful HIV prevention agenda should include trans-specific interventions supporting oral PrEP and exploring long-acting PrEP strategies for TGW.

Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors.

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

Impact of Estimated Pre-Exposure Prophylaxis (PrEP) Adherence Patterns on Bone Mineral Density in a Large PrEP Demonstration Project.

Bone mineral density (BMD) declines due to tenofovir-containing pre-exposure prophylaxis (PrEP) have varied among PrEP demonstration projects, potentially related to variable adherence. Characterization of BMD changes in highly adherent individuals, estimated via tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS), can assist clinicians when counseling patients. Cisgender men who have sex with men and transwomen in the optional dual-energy X-ray absorptiometry (DXA) substudy of a large, international, open-label PrEP demonstration project, the iPrEx-open-label extension (OLE) study underwent DXA scans and DBS collection every 24 weeks, with average weekly dosing adherence patterns (2, 4, and 7 doses/week) estimated from validated TFV-DP cut-offs. The mean percent BMD change was estimated in strata of average weekly adherence by using a linear mixed-effects model to calculate the BMD decline in highly adherent individuals on PrEP for the first time. DXA/DBS data were available for 254 individuals over a median of 24 weeks in iPrEx-OLE from June 2011 to December 2013. The percent decline in spine BMD was monotonically associated with strata of increasing average weekly adherence (p < .001 trend); the p value for trends using hip BMD measurements was .07. Individuals with estimated daily adherence experienced a 1.2% decrease in spine BMD and a 0.5% drop in hip BMD. In highly adherent PrEP users, we found a lower-than-expected drop in BMD when compared with previous studies. This drop is likely not clinically significant for most PrEP users. However, for those at the highest risk of fracture who plan prolonged PrEP use, alternate PrEP strategies could be considered.

Health Survey in a Peruvian health system (ENSSA): design, methodology and general results.

OBJECTIVE: To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured. RESULTS: There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. RESULTS: The 25,000 homes were interviewed, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. CONCLUSIONS: This survey is the first performed in the population of EsSalud affiliates, applied at the national level, and has socio-economic and demographic data of the insured, their distribution, risk factors of health, prevalence of health problems and the degree of access to health services.

Brief Report: Cocaine Use and Pre-exposure Prophylaxis: Adherence, Care Engagement, and Kidney Function.

BACKGROUND: Concomitant use of cocaine and HIV pre-exposure prophylaxis (PrEP) raises important clinical questions around adherence, retention in care, and renal toxicity. METHODS: We assessed the associations of confirmed cocaine use with PrEP adherence (both ascertained through objective measures), care engagement, and renal function in the iPrEx open-label extension. Cocaine use was measured in scalp hair samples and categorized as light (500-3000 pg/mg) and moderate to heavy (>3000 pg/mg). PrEP adherence in the first 3 months was measured through plasma tenofovir concentrations. Disengagement from PrEP care was defined as a gap in follow-up greater than 4 months. Serum creatinine was assessed at baseline and quarterly visits. RESULTS: Of the 400 participants included in this analysis, 90% were men who have sex with men, 10% transgender women, 74% Hispanic/Latino; 21% tested positive for cocaine use in the last 3 months. In adjusted analysis, light cocaine use [adjusted odds ratio 2.10 (95% confidence interval: 1.07 to 4.14)] and moderate to heavy use [adjusted odds ratio 2.32 (1.08 to 5.00)] were associated with greater odds of having plasma tenofovir concentrations below the level of quantitation. Participants with moderate to heavy use had a nearly 3-fold higher rate of disengagement from PrEP care compared with nonusers (adjusted hazard ratio 2.90 [1.48 to 5.66]). We found no statistically or clinically significant differences in creatinine clearance and serum creatinine between participants who tested positive for cocaine and those who did not. CONCLUSIONS: Cocaine use decreases PrEP adherence and care engagement. Comprehensive approaches are needed to reduce cocaine use and enhance engagement along the PrEP care continuum.

The impact and cost-effectiveness of combined HIV prevention scenarios among transgender women sex-workers in Lima, Peru: a mathematical modelling study.

BACKGROUND: HIV incidence remains high among transgender women in Lima, Peru, most of whom report sex work. On the basis of a stakeholder analysis and health system capacity assessment, we designed a mathematical model to guide HIV programmatic planning among transgender women sex workers (TWSW) in Lima. METHODS: Using a deterministic compartmental model, we modelled HIV transmission among TWSW, their stable partners, and their clients to estimate the impact and cost-effectiveness of combinations of interventions compared with the standard of care on reducing HIV incidence over a 10-year period. We simulated HIV transmission accounting for differences in sexual positioning in anal intercourse and condom use by partner type and fitted the model to HIV surveillance data using Latin hypercube sampling. The interventions we considered were 15% relative increase in condom use with clients and 10% relative increase with stable partners; increase in antiretroviral treatment (ART) coverage at CD4 count lower than 500 cells per mm3 and greater than or equal to 500 cells per mm3; and 15% pre-exposure prophylaxis (PrEP) coverage using generic and branded formulations. We considered a basic scenario accounting for current limitations in the Peruvian HIV services and an enhanced scenario assuming achievement of the UNAIDS 90-90-90 targets and general improvements in HIV services. The 50 best fits according to log-likelihood were used to give the minimum and maximum values of intervention effect for each combination. We used disability-adjusted life-years (DALYs) to measure the negative health outcomes associated with HIV infection that could be averted through the interventions investigated and calculated incremental cost-effectiveness ratios to compare their cost-effectiveness. FINDINGS: Under the basic scenario, combining the four interventions of increasing condom use with clients and stable partners, extending ART to people with CD4 count greater than or equal to 500 cells per mm3, and 15% PrEP coverage with generic drugs would avert 47% (range 27-51) of new infections in TWSW, their clients, and their stable partners over 10 years, with an incremental cost-effectiveness ratio of US$509 per DALY averted. Under the enhanced scenario, this strategy would avert 61% (44-64) of new infections among this population with an incremental cost-effectiveness ratio of $1003 per DALY averted. Under both scenarios, implementation of this strategy approaches or surpasses the 50% incidence reduction goal and would represent a cost-effective use of country resources if generic PrEP drugs are used. The total cost of implementing this strategy under the enhanced scenario would be approximately $1·2 million per year over 10 years, corresponding to 10% of the current Global Fund's yearly contribution in Peru. INTERPRETATION: Investments in HIV services among TWSW in Lima would be cost-effective, even under stringent cost-effectiveness criteria when accounting for setting-specific resource constraints. Notable improvements in HIV testing rates, innovative interventions to increase condom use, and reduced PrEP costs will be key to achieving the 50% incidence reduction goal. Modelling studies incorporating stakeholders' perspectives and health system assessments can bring added value to HIV policy making. FUNDING: National Institutes of Health.

Health survey in a peruvian health system (ENSSA): design, methodology and general results / Encuesta de salud en un sistema sanitario peruano (ENSSA): diseño, metodología y resultados generales

ABSTRACT OBJECTIVE To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured. RESULTS There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. RESULTS The 25,000 homes were interviewed, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. CONCLUSIONS This survey is the first performed in the population of EsSalud affiliates, applied at the national level, and has socio-economic and demographic data of the insured, their distribution, risk factors of health, prevalence of health problems and the degree of access to health services.

RESUMEN OBJETIVO Reportar el diseño, metodología y resultados iniciales de la Encuesta Nacional Socioeconómica de Acceso a la Salud de los Asegurados de EsSalud. MÉTODOS La Encuesta se ejecutó en los 24 departamentos del país. Los temas investigados fueron: características de la vivienda y miembros del hogar, educación, salud, empleo e ingreso y gastos del hogar. Se realizó un tipo de muestreo bi-etápico: la unidad primaria de muestreo estuvo conformada por conglomerados compuestos por una manzana dentro del ámbito de cobertura del centro asistencial; la unidad secundaria de muestreo fueron viviendas particulares donde habitaba al menos un asegurado a EsSalud. Se analizaron los datos de 62,659 afiliados y se muestran porcentajes ajustados por el factor de expansión. Para las comparaciones, se utilizó la prueba de chi-cuadrado. RESULTADOS Se entrevistaron 25000 viviendas, encuestándose a 79,874 personas, de las cuales 62,659 eran afiliados a EsSalud. Los afiliados son principalmente varones (50.6%) con un nivel de educación técnico superior (39.7%). La población afiliada cuenta mayoritariamente con vivienda independiente (95.0%) y propia (68.1%). Solo el 34.5% de los asegurados practica algún deporte o ejercicio físico. El 14.0% de la población padece de alguna enfermedad crónica; el 3.5% presenta diabetes; y el 7.1%, hipertensión arterial. En los últimos tres meses, el 35.4% de los afiliados necesitaron atención médica; de estos, solo el 73.1% recibieron atención sanitaria y el 10.9% restante se atendieron en farmacias o servicios no formales de atención en salud. CONCLUSIONES Esta encuesta es la primera realizada en la población de afiliados a EsSalud, aplicada a nivel nacional, y cuenta con datos socioeconómicos y demográficos de los asegurados, su distribución, factores de riesgo de la salud, prevalencia de los problemas de salud y el grado de acceso a los servicios de salud.

The Role of Social Relationships in PrEP Uptake and Use Among Transgender Women and Men Who Have Sex with Men.

Qualitative studies suggest that social relationships play an important role in HIV pre-exposure prophylaxis (PrEP) use, but there have been few quantitative assessments of the role of social relationships in PrEP uptake or adherence. We examined the association between disclosure of study participation or LGBT identity and PrEP use in the 1603 HIV-negative participants enrolled in the iPrEx OLE study. We also evaluated the association between LGBT social group involvement and PrEP use. Study participation disclosure to parents and LGBT identity disclosure to anyone in a participant's social network were associated with greater PrEP uptake. Study participation disclosure to partners was associated with higher probability of having protective PrEP drug concentrations compared [risk difference 0.15 95% CI (0.01, 0.30)]. For each additional type of LGBT organization a participant was involved in, the probability of PrEP uptake and having protective drug concentrations increased by 0.04 [95% CI (0.03, 0.06)] and 0.04 (95% CI (0.02, 0.07)] respectively. Overall, social context was associated with PrEP use in iPrEx OLE, and should be taken into consideration when designing future PrEP implementation programs.

Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine.

Background: Antiretroviral drugs have been associated with changes in lipids, fat mass and dat distribution. Tenofovir disoproxil fumarate (TDF) has been shown to have a more favorable metabolic profile than other drugs in its class. However, the metabolic effects of TDF in preexposure prophylaxis (PrEP) are unknown. Methods: We evaluated the effects of TDF/emtricitabine (FTC) on lipids and body composition in a blinded, placebo-controlled PrEP trial. Participants enrolled in a metabolic subcohort (N = 251, TDF/FTC; N = 247, placebo) consented to fasting lipid panels, dual-energy X-ray absorptiometry scans for body composition, and pharmacologic testing of drug metabolites at baseline and every 24 weeks thereafter. Results: Lean body mass was stable and unaffected by TDF/FTC. Body weight increased in both groups but was lower on TDF/FTC through week 72. This difference was explained by lower fat accumulation on TDF/FTC. The net median percent difference (standard error, P value) for TDF/FTC vs placebo at week 24 was -0.8% (0.4%, P = .02), +0.3% (0.4%, P = .46), and -3.8% (1.4%, P = .009) for total, lean, and fat mass, respectively. There was no apparent differential regional fat accumulation on TDF/FTC. Decreases in cholesterol, but not triglycerides, were seen in TDF/FTC participants, with detectable drug levels compared to placebo. Conclusions: TDF/FTC for PrEP showed cholesterol reductions and appeared to transiently suppress the accumulation of weight and body fat compared to placebo. There was no evidence of altered fat distribution or lipodystrophy during daily oral TDF/FTC PrEP. Clinical Trials Registration: NCT00458393.

HIV sero disclosure among men who have sex with men and transgender women on HIV pre-exposure prophylaxis.

HIV pre-exposure prophyalxis (PrEP) might lead individuals to view serodisclosure as unnecessary. We examined the prevalence of non-disclosure and lack of knowledge of partner status in a global cohort of men who have sex with men (MSM) and transgender women (TW) enrolled in the iPrEx Open Label Extension (OLE). We calculated prevalence ratios by fitting a logistic model and estimating predicted probabilities using marginal standardization. Prevalence of non-disclosure and lack of knowledge of partner status were highest in Thailand (73% and 74%, respectively) and lowest in the USA (23% and 37%, respectively). In adjusted analyses, PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status (p-values>0.05). We found that relationship characteristics were significantly associated with both outcomes. Non-disclosure was higher among casual (adjusted prevalence ratio [aPR] 1.54, [95% confidence interval 1.24-1.84]) and transactional sex partners (aPR 2.03, [1.44-2.62]), and among partners whom participants have known only minutes or hours before their first sexual encounter (aPR 1.62, [1.33-1.92]). Similarly, participants were less likely to know the HIV status of casual partners (aPR 1.50, [1.30-1.71]), transactional sex partners (aPR 1.62, [1.30-1.95]), and those they have known for only days or weeks (aPR 1.13, [0.99-1.27]) or minutes or hours (aPR 1.27, [1.11-1.42]). Our findings underscore the role of dyadic factors in influencing serodisclosure. Comprehensive risk reduction counseling provided in conjunction with PrEP that address relationship characteristics are needed to help patients navigate discussions around HIV status.

Brief Report: Recovery of Bone Mineral Density After Discontinuation of Tenofovir-Based HIV Pre-exposure Prophylaxis.

BACKGROUND: Oral tenofovir disoproxil fumarate (TDF) for HIV prevention and treatment is associated with decreases in bone mineral density (BMD). Previous reports suggest that these changes may be reversible after discontinuation of TDF. SETTING: A metabolic substudy of 498 participants in a randomized, placebo-controlled HIV prevention trial of oral coformulated TDF with emtricitabine (TDF/FTC, Truvada) for HIV pre-exposure prophylaxis (PrEP) enrolling a global sample of men who have sex with men and trans women. METHODS: Participants underwent dual X-ray absorptiometry to quantify bone mineral density (BMD) in the hip and spine during PrEP and at 2 visits after stopping (median of 23 and 79 weeks post-PrEP, respectively). Results are stratified by pharmacologic measure of TDF/FTC adherence. RESULTS: There was no significant difference in change in hip/spine BMD at any time point between placebo and those with low adherence. Adherent participants had a mean (standard error) BMD change at TDF/FTC discontinuation of -1.02% (0.24) in the hip and -1.84% (0.36) in the spine. After stop, annualized BMD increases of 1.13% per year (0.27) in hip and 1.81% per year (0.36) in spine BMD were observed in adherent participants compared with 0.19% (0.16) and 0.74% (0.21) in the placebo group, respectively (P = 0.003, both comparisons). On average, BMD returned to baseline levels by 1 year after PrEP stop. Recovery was consistent across age, baseline BMD z-score, and treatment duration. CONCLUSIONS: Mean BMD returns to baseline levels within 12-18 months after TDF-based PrEP discontinuation in both hip and spine with consistency across participant subgroups. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT00458393.

International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status.

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

Towards a fair consideration of PrEP as part of combination HIV prevention in Latin America.

INTRODUCTION: Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. DISCUSSION: Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. CONCLUSIONS: PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost-effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full-scale PrEP programmes.

Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study.

BACKGROUND: As pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine for the prevention of HIV infection is rolled out internationally, strategies to maintain effectiveness and to minimise adverse effects merit consideration. In this study, we aimed to assess reductions in renal function and predictors of renal toxicity in a large open-label study of PrEP. METHODS: As part of the iPrEx open-label extension (OLE) study, men who have sex with men or transgender women aged 18-70 years who were HIV negative and had participated in three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the USA were enrolled into an open-label PrEP study. There were no restrictions on current renal function for enrolment into iPrEx OLE, in which participants were given combination tablets of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) and advised to take one tablet per day. At follow-up sessions every 12 weeks, participants' creatinine clearance on PrEP was estimated and in a subset of participants, hair samples were collected to measure tenofovir and emtricitabine concentrations (a measure of adherence and exposure) via liquid-chromatography-tandem-mass-spectrometry. Reductions in creatinine clearance from baseline were calculated and predictors of decline were identified by use of multivariate models. iPrEx is registered with ClinicalTrials.com, number NCT00458393. FINDINGS: Baseline characteristics were similar between all participants in iPrEx-OLE (1224 participants with 7475 person-visits) and those participating in the hair substudy (220 participants with 1114 person-visits). During a median of 72 weeks, the mean decline in creatinine clearance was -2·9% (95% CI -2·4 to -3·4; ptrend<0·0001), but declines were greater for those who started PrEP at older ages: participants aged 40-50 years at baseline had declines of -4·2% (95% CI -2·8 to -5·5) and participants older than 50 years at baseline had declines of -4·9% (-3·1 to -6·8). In multivariate models, age and baseline creatinine clearance less than 90 mL/min predicted declines in renal function. We identified a monotonic association between percentage decrease in creatinine clearance and the number of doses of tenofovir disoproxil fumarate and emtricitabine taken per week, as estimated by hair concentrations of tenofovir and emtricitabine (ptrend=0·008). INTERPRETATION: Our data suggest that the frequency of safety monitoring for PrEP might need to be different between age groups and that pharmacological measures can monitor for toxic effects as well as adherence. FUNDING: National Institutes of Health.

Transgender Women in Clinical Trials of Pre-Exposure Prophylaxis.

Lessons were learned with trans women who participated (as volunteers and investigators) in trials of HIV pre-exposure prophylaxis (PrEP). Trans women are not men. Compared with men who have sex with men, trans women trial participants were more likely to be involved with transactional sex, had more sexual partners, and were less likely to have PrEP medications detected in blood. Trans women define themselves differently in different cultures. One best practice is to ask at least 2 gender questions: sex assigned at birth and current gender. More information is needed to fully situate PrEP efficacy for trans women, including analysis of drug-drug interactions between PrEP medications and feminizing hormones and PrEP drug penetration into neovaginal tissues. Including trans women in studies is helpful only if their participation is specifically reported, as could occur in a table of baseline characteristics of the enrolled cohort. Gender-affirming care is important to foster appropriate uptake and use of PrEP. Such care includes use of preferred pronouns and names, safety to use the bathroom of choice, and access to gender-affirming hormone therapy and surgery. The consistent finding that PrEP works when taken across diverse populations having diverse practices related to gender, sexual intercourse, and hormone use provides a basis for offering PrEP to people at substantial risk of acquiring HIV although some subgroups may not have been fully represented in trials. Nonetheless, specific PrEP implementation science for trans women (and men) is essential to develop best practices for PrEP delivery and use.

Self-reported Recent PrEP Dosing and Drug Detection in an Open Label PrEP Study.

Monitoring adherence to pre-exposure prophylaxis (PrEP) is part of the recommended package for PrEP prescribing, yet ongoing concerns about how to do so confidently are exacerbated by gross discrepancies in reported and actual use in clinical trials. We evaluated concordance between reports of recent PrEP dosing collected via neutral interviewing and drug quantitation in the iPrEx open-label extension, where participants (n = 1172) had the choice to receive or not receive PrEP. Self-report of recent dosing (at least one PrEP dose in the past 3-day) was the most common report (84 % of participants), and among these 83 % did have quantifiable levels of drug. The vast majority of those reporting no doses in the past 3-day (16 % of the sample) did not have quantifiable levels of drug (82 %). Predictors of over-report of dosing included younger age and lower educational attainment. Monitoring recent PrEP use through neutral interviewing may be a productive approach for clinicians to consider in implementation of real-world PrEP. Strategies to capture longer term or prevention-effective PrEP use, particularly for younger cohorts, are needed.