HIV pre-exposure prophylaxis in men who have sex with men and transgender women: a secondary analysis of a phase 3 randomised controlled efficacy trial.

For maximum effect pre-exposure prophylaxis should be targeted to the subpopulations that account for the largest proportion of infections (population-attributable fraction [PAF]) and for whom the number needed to treat (NNT) to prevent infection is lowest. We aimed to estimate the PAF and NNT of participants in the iPrEx (Pre-Exposure Prophylaxis Initiative) trial. The iPrEx study was a randomised controlled efficacy trial of pre-exposure prophylaxis with coformulated tenofovir disoproxil fumarate and emtricitabine in 2499 men who have sex with men (MSM) and transgender women. Participants aged 18 years or older who were male at birth were enrolled from 11 trial sites in Brazil, Ecuador, Peru, South Africa, Thailand, and the USA. Participants were randomly assigned (1:1) to receive either a pill with active pre-exposure prophylaxis or placebo, taken daily. We calculated the association between demographic and risk behaviour during screening and subsequent seroconversion among placebo recipients using a Poisson model, and we calculated the PAF and NNT for risk behaviour subgroups. The iPrEx trial is registered with ClinicalTrials.gov, NCT00458393. Patients were enrolled between July 10, 2007, and Dec 17, 2009, and were followed up until Nov 21, 2010. Of the 2499 MSM and transgender women in the iPrEx trial, 1251 were assigned to pre-exposure prophylaxis and 1248 to placebo. 83 of 1248 patients in the placebo group became infected with HIV during follow-up. Participants reporting receptive anal intercourse without a condom seroconverted significantly more often than those reporting no anal sex without a condom (adjusted hazard ratio [AHR] 5·11, 95% CI 1·55-16·79). The overall PAF for MSM and transgender women reporting receptive anal intercourse without a condom was 64% (prevalence 60%). Most of this risk came from receptive anal intercourse without a condom with partners with unknown serostatus (PAF 53%, prevalence 54%, AHR 4·76, 95% CI 1·44-15·71); by contrast, the PAF for receptive anal intercourse without a condom with an HIV-positive partner was 1% (prevalence 1%, AHR 7·11, 95% CI 0·70-72·75). The overall NNT per year for the cohort was 62 (95% CI 44-147). NNTs were lowest for MSM and transgender women self-reporting receptive anal intercourse without a condom (NNT 36), cocaine use (12), or a sexually transmitted infection (41). Having one partner and insertive anal sex without a condom had the highest NNTs (100 and 77, respectively). Pre-exposure prophylaxis may be most effective at a population level if targeted toward MSM and transgender women who report receptive anal intercourse without a condom, even if they perceive their partners to be HIV negative. Substance use history and testing for STIs should also inform individual decisions to start pre-exposure prophylaxis. Consideration of the PAF and NNT can aid in discussion of the benefits and risks of pre-exposure prophylaxis with MSM and transgender women. National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation.

Buchbinder SP ，Glidden DV ，Liu AY ，McMahan V ，Guanira JV ，Mayer KH ，Goicochea P ，Grant RM ... -  《-》

HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial.

Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women. The iPrEx trial was a randomised controlled trial of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate compared with placebo in men who have sex with men (MSM) and transgender women, followed by an open-label extension. Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. We did unplanned exploratory analyses to investigate differences in PrEP outcomes among transgender women and between transgender women and MSM. Of the 2499 participants enrolled in the randomised controlled trial, 29 (1%) identified as women, 296 (12%) identified as trans, 14 (1%) identified as men but reported use of feminising hormones, such that 339 (14%) reported one or more characteristics and are classified as transgender women for the purpose of this study. Compared with MSM, transgender women more frequently reported transactional sex, receptive anal intercourse without a condom, or more than five partners in the past 3 months. Among transgender women, there were 11 HIV infections in the PrEP group and ten in the placebo group (hazard ratio 1·1, 95% CI 0·5-2·7). In the PrEP group, drug was detected in none of the transgender women at the seroconversion visit, six (18%) of 33 seronegative transgender women (p=0·31), and 58 (52%) of 111 seronegative MSM (p<0·0001). PrEP use was not linked to behavioural indicators of HIV risk among transgender women, whereas MSM at highest risk were more adherent. PrEP seems to be effective in preventing HIV acquisition in transgender women when taken, but there seem to be barriers to adherence, particularly among those at the most risk. Studies of PrEP use in transgender women populations should be designed and tailored specifically for this population, rather than adapted from or subsumed into studies of MSM. US National Institutes of Health and the Bill & Melinda Gates Foundation.

Deutsch MB ，Glidden DV ，Sevelius J ，Keatley J ，McMahan V ，Guanira J ，Kallas EG ，Chariyalertsak S ，Grant RM ，iPrEx investigators ... -  《Lancet HIV》

Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study.

Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation.

Molina JM ，Charreau I ，Spire B ，Cotte L ，Chas J ，Capitant C ，Tremblay C ，Rojas-Castro D ，Cua E ，Pasquet A ，Bernaud C ，Pintado C ，Delaugerre C ，Sagaon-Teyssier L ，Mestre SL ，Chidiac C ，Pialoux G ，Ponscarme D ，Fonsart J ，Thompson D ，Wainberg MA ，Doré V ，Meyer L ，ANRS IPERGAY Study Group ... -  《Lancet HIV》

Bacterial sexually transmitted infections among men who have sex with men and transgender women using oral pre-exposure prophylaxis in Latin America (ImPrEP): a secondary analysis of a prospective, open-label, multicentre study.

The global burden of sexually transmitted infections (STIs) poses a challenge in the context of HIV pre-exposure prophylaxis (PrEP) programmes. We aimed to explore factors associated with prevalent, incident, and recurrent STIs in men who have sex with men (MSM) and transgender women on PrEP in Brazil, Mexico, and Peru. ImPrEP was a prospective, single-arm, open-label, multicentre study that enrolled MSM and transgender women in the context of the public health systems of Brazil (14 sites), Mexico (four sites), and Peru (ten sites) between February, 2018, and June, 2021. Eligibility criteria followed regional PrEP guidelines at the study start, including participants aged 18 years and older, not living with HIV, and reporting at least one of the following in the previous 6 months: condomless anal sex (CAS), anal sex with partner(s) living with HIV, any bacterial STI, or transactional sex. Eligible participants were screened and enrolled on the same day to receive daily oral PrEP (tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg). We assessed three outcomes: prevalent bacterial STIs, incident bacterial STIs, and recurrent bacterial STIs. Testing occurred at baseline and quarterly for syphilis, anorectal chlamydia, and anorectal gonorrhoea. Behavioural data were collected at baseline and quarterly. The study was registered with the Brazilian Registry of Clinical Trials, U1111-1217-6021. Among all 9509 participants included in the ImPrEP study (3928 [41·3%] in Brazil, 3288 [34·6%] in Mexico, and 2293 [24·1%] in Peru), 8525 (89·7%) had available STI results at baseline and were included in the prevalent STI analysis, and 7558 (79·5%) had available STI results during follow-up and were included in the incident and recurrent STI analyses. 2184 (25·6%) of 8525 participants had any bacterial STI at baseline. STI incidence during follow-up was 31·7 cases per 100 person-years (95% CI 30·7-32·7), with the highest rate for anorectal chlamydia (11·6 cases per 100 person-years, 95% CI 11·0-12·2), followed by syphilis (10·5 cases per 100 person-years, 9·9-11·1) and anorectal gonorrhoea (9·7 cases per 100 person-years, 9·2-10·3). Although only 2391 (31·6%) of 7558 participants had at least one STI during follow-up, 915 (12·1%) participants had recurrent diagnoses, representing 2328 (61·2%) of 3804 incident STI diagnoses. Characteristics associated with prevalent, incident, and recurrent STIs included younger age, multiple sex partners, receptive CAS, substance use, and previous STI diagnoses at baseline (incident or recurrent only). Our findings underscore the nuanced dynamics of STI transmission among MSM and transgender women across Latin America, highlighting an urgent need for tailored interventions to mitigate STI burden effectively, especially among the most susceptible individuals. Unitaid, WHO, and ministries of health (Brazil, Mexico, and Peru). For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Torres Silva MS ，Torres TS ，Coutinho C ，Ismério Moreira R ，da Costa Leite I ，Cunha M ，da Costa Leite PHA ，Cáceres CF ，Vega-Ramírez H ，Konda KA ，Guanira J ，Valdez Madruga J ，Wagner Cardoso S ，Benedetti M ，Pimenta MC ，Hoagland B ，Grinsztejn B ，Gonçalves Veloso V ，ImPrEP Study Group ... -  《Lancet HIV》

Retention, engagement, and adherence to pre-exposure prophylaxis for men who have sex with men and transgender women in PrEP Brasil: 48 week results of a demonstration study.

PrEP Brasil was a demonstration study to assess feasibility of daily oral tenofovir diphosphate disoproxil fumarate plus emtricitabine provided at no cost to men who have sex with men (MSM) and transgender women at high risk for HIV within the Brazilian public health system. We report week 48 pre-exposure prophylaxis (PrEP) retention, engagement, and adherence, trends in sexual behaviour, and incidence of HIV and sexually transmitted infections in this study cohort. PrEP Brasil was a 48 week, open-label, demonstration study that assessed PrEP delivery at three referral centres for HIV prevention and care in Rio de Janeiro, Brazil (Fundação Oswaldo Cruz), and São Paulo, Brazil (Universidade de São Paulo and Centro de Referência e Treinamento em DST e AIDS). Eligible participants were MSM and transgender women who were HIV negative, aged at least 18 years, resident in Rio de Janeiro or São Paulo, and reported one or more sexual risk criteria in the previous 12 months (eg, condomless anal sex with two or more partners, two or more episodes of anal sex with an HIV-infected partner, or history of sexually transmitted infection [STI] diagnosis). Participants were seen at weeks 4, 12, 24, 36, and 48 for PrEP provision, clinical and laboratory evaluation, and HIV testing. Computer-assisted self-interviews were also done at study visits 12, 24, 36, and 48, and assessed sexual behaviour and drug use. PrEP retention was defined by attendance at the week 48 visit, PrEP engagement was an ordinal five-level variable combining presence at the study visit and drug concentrations, and PrEP adherence was evaluated by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models were used to quantify the association of variables with high adherence (≥4 doses per week). The study is registered with ClinicalTrials.gov, number NCT01989611. Between April 1, 2014, and July 8, 2016, 450 participants initiated PrEP, 375 (83%) of whom were retained until week 48. At week 48, 277 (74%) of 375 participants had protective drug concentrations consistent with at least four doses per week: 183 (82%) of 222 participants from São Paulo compared with 94 (63%) of 150 participants from Rio de Janeiro (adjusted odds ratio 1·88, 95% CI 1·06-3·34); 119 (80%) of 148 participants who reported sex with HIV-infected partners compared with 158 (70%) of 227 participants who did not (1·78, 1·03-3·08); 67 (87%) of 77 participants who used stimulants compared with 210 (71%) of 298 participants who did not (2·23, 1·02-4·92); and 232 (80%) of 289 participants who had protective concentrations of tenofovir disphosphate at week 4 compared with 42 (54%) of 78 participants who did not (3·28, 1·85-5·80). Overall, receptive anal sex with the last three partners increased from 45% at enrolment to 49% at week 48 (p=0·17), and the mean number of sexual partners in the previous 3 months decreased from 11·4 (SD 28·94) at enrolment to 8·3 (19·55) at week 48 (p<0·0013). Two individuals seroconverted during follow-up (HIV incidence 0·51 per 100 person-years, 95% CI 0·13-2·06); both of these patients had undetectable tenofovir concentrations at seroconversion. Our results support the effectiveness and feasibility of PrEP in a real-world setting. Offering PrEP at public health-care clinics in a middle-income setting can retain high numbers of participants and achieve high levels of adherence without risk compensation in the investigated populations. Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Secretaria de Vigilancia em Saúde, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, and Fundação de Amparo à Pesquisa do Estado de São Paulo.

Grinsztejn B ，Hoagland B ，Moreira RI ，Kallas EG ，Madruga JV ，Goulart S ，Leite IC ，Freitas L ，Martins LMS ，Torres TS ，Vasconcelos R ，De Boni RB ，Anderson PL ，Liu A ，Luz PM ，Veloso VG ，PrEP Brasil Study Team ... -  《Lancet HIV》