The effectiveness of tenofovir-based pre-exposure prophylaxis for prevention of HIV acquisition among sub-Saharan African women at high risk: a systematic review.

INTRODUCTION: women in sub-Saharan Africa (SSA) are disproportionately affected by the HIV epidemic. In 2019, they constituted 59% of new infections; thus, they remain a key population for control. Public health interventions to prevent acquisition of HIV in this high-risk population are urgently needed. Tenofovir-based pre-exposure prophylaxis (TFV-PrEP) has been shown to reduce HIV infections in other key populations. However, comprehensive evidence regarding TFV-PrEP effectiveness in women living in SSA has not been determined. Therefore, we undertook a systematic review to determine the effectiveness of tenofovir-1% (TFV-1%) vaginal gel, oral tenofovir (TFV) and tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis for primary acquisition of HIV in at-risk women living in SSA. METHODS: OVID Medline, Embase, CENTRAL, Web of Science and Clinical Trials.gov were searched for eligible studies from 1st January 2020 to 31st July 2020. Only randomised controlled trials (RCTs) conducted in women living in SSA were included. Measures of effectiveness (hazard ratios (HR), incidence rate ratios (IRR)) were extracted from individual studies to determine the effectiveness of TFV-PrEP in preventing HIV infection among at-risk women living in SSA. RESULTS: from 2002 non-duplicate articles, four RCTs evaluating the effectiveness of one or more of the interventions against placebos were included. TFV-1% vaginal gel, oral TDF or TDF-FTC were not effective in preventing the acquisition of HIV infection in women living in SSA. However, poor adherence by study participants could have confounded the true effectiveness of TFV-PrEP in this high risk population. Meta-analysis was not conducted given the limited number of eligible studies identified from the search. CONCLUSION: the current evidence does not support the effectiveness of TFV-PrEP for HIV in SSA women. More studies aimed at addressing factors driving low adherence to HIV interventions in this high risk population are urgently needed in order to improve the design of future RCTs leading to the determination of more reliable estimates of TFV-1% vaginal gel or oral TDF or TDF-FTC effectiveness. Protocol registration: this systematic review was not registered in PROSPERO.

Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection.

Introduction: Pregnancy is a period of elevated HIV risk in high-burden settings, motivating the need for prevention tools that are both safe for use and effective during pregnancy. Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) is recommended by the World Health Organization, including for pregnant and postpartum women at substantial risk of HIV infection. Although TDF use during pregnancy appears generally safe, data on PrEP use during pregnancy remain limited.Areas covered: We provide an overview of the clinical pharmacology and efficacy of daily TDF-based PrEP and summarize current evidence on the safety of PrEP use by pregnant HIV-uninfected women. We synthesize relevant studies assessing pregnancy outcomes among pregnant women who are living with HIV (WLHIV) and using TDF-based therapy. Finally, we make comparison to the safety profiles of other emerging HIV prevention options.Expert opinion: The current evidence indicates that TDF/FTC PrEP use is not associated with increased risk of adverse pregnancy and early infant growth outcomes. While safety data are generally reassuring, there is need for continued accrual of data on growth and pregnancy outcomes in PrEP research, implementation projects, and controlled pharmacokinetic studies to support current evidence and to understand concentration-efficacy relationship in pregnant women.

Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide-based ART.

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa.

BACKGROUND: The World Health Organisation recommends the use of tenofovir-containing pre-exposure prophylaxis (PrEP) as an additional Human Immunodeficiency Virus (HIV) prevention choice for men and women at substantial risk of HIV infection. PrEP could fill an important HIV prevention gap, especially for sexually active young women who are limited in their ability to negotiate mutual monogamy or condom use. As PrEP is scaled up in high HIV incidence settings, it is crucial to consider the importance of early identification of HIV infection during PrEP use, to allow for rapid discontinuation of PrEP to reduce the risk of antiretroviral (ARV) resistance. The purpose of this case study is to provide this critical evidence. CASE PRESENTATION: This report describes a 20-year-old woman in a HIV sero-discordant relationship who initiated oral PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)) through a demonstration project (CAPRISA 084) in October 2017. Despite good adherence throughout her PrEP use, she tested HIV antibody positive at month nine of study participation. Retrospective testing showed increasing HIV viral load over time, and retrospective use of fourth-generation rapid HIV tests showed HIV detection (positive antigen/antibody) at month one. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection. The participant was referred to infectious diseases for further management of her HIV infection and was initiated on a first line, tenofovir-sparing regimen. At the time of this report (January 2020), the participant had been on ARV- therapy (ART) for 13 months and had no signs of either clinical, immunologic or virologic failure. CONCLUSIONS: This case report highlights the importance of appropriate HIV screening during wider oral PrEP scale-up in high HIV incidence settings to circumvent the consequences of prolonged dual therapy in an undiagnosed HIV infection and in turn prevent ARV resistance.

Pharmacology and drug interactions with HIV PrEP in transgender persons receiving gender affirming hormone therapy.

INTRODUCTION: Transgender persons are at increased risk of HIV infection and would benefit from pre-exposure prophylaxis (PrEP) use. However, barriers to healthcare and a lack of data regarding PrEP efficacy among transgender persons limits use. A related issue is whether a drug-drug interaction (DDI) exists between gender affirming hormone therapy (GAHT) and PrEP. Recently, small pharmacokinetic studies were conducted to assess this interaction. AREAS COVERED: This review will assess the pharmacology of PrEP agents, existing data regarding potential DDIs between GAHT and PrEP, and hypothetical mechanisms for these DDIs. A summary will be provided on implications for PrEP use among transgender persons. EXPERT OPINION: Theoretically, DDIs are not expected between GAHT and PrEP. However, among transgender women (TGW) on GAHT, small studies identified a minor DDI between GAHT and tenofovir/emtricitabine (TFV/FTC), with TFV/FTC exposures ~12-27% lower among TGW vs. cisgender men. The mechanism of DDIs is unclear and requires further study. For perspective, median TFV/FTC concentrations were still within the range of median concentrations reported across controlled pharmacokinetic studies. TFV-disphosphate/FTC-triphosphate concentrations were similar between TGW and cisgender men. In summary, TDF/FTC likely reaches protective concentrations and should continue to be offered as PrEP for transgender persons.

The HIV Pre-exposure Prophylaxis (PrEP) Cascade at NYC Sexual Health Clinics: Navigation Is the Key to Uptake.

BACKGROUND: Clinics providing sexual health care pose unique opportunities to implement HIV pre-exposure prophylaxis (PrEP) programs. The PrEP program at New York City's Sexual Health Clinics provides intensive on-site navigation for linkage to PrEP care. We assessed uptake of this intervention. METHODS: We categorized men who have sex with men (MSM) without HIV hierarchically as having had (1) HIV post-exposure prophylaxis (PEP) use (past year); or (2) selected sexually transmitted infections (STI) (past year); or (3) HIV-diagnosed sex/needle-sharing partners (past 6 months); or (4) expressed interest in PrEP (day of clinic visit). We constructed PrEP cascades and used multivariable regression to examine acceptance of PrEP navigation, referral to a PrEP provider, linkage (<60 days), and PrEP prescription. RESULTS: One thousand three hundred one of 2106 PrEP (62%) patients accepted navigation. Of those, 55% (718/1301) were black or Hispanic MSM. STI and PEP patients had lowest navigation acceptance levels (35%-46%). Of navigated patients, 56% (628/1114) accepted referrals, 46% (288/628) linked to PrEP providers, and 82% (235/288) were prescribed PrEP; overall, 11% of those offered navigation (235/2106) received prescriptions. Navigated MSM with PEP history [adjusted prevalence ratio (aPR) 1.34, 95% confidence interval (CI): 1.16 to 1.56)], previous STI (aPR 1.28, 95% CI: 1.12 to 1.45), or HIV-diagnosed partners (aPR 1.18, 95% CI: 1.01 to 1.37) were more likely than those with PrEP interest to accept referrals. Probability of linkage varied by insurance status; prescription did not vary by patient factors. CONCLUSIONS: Although MSM in key priority groups (eg, previous STI) showed low navigation uptake, those who accepted navigation were likely to be referred for PrEP, suggesting a need for expanded up-front engagement.

Inhibitory Effects of Probenecid on Pharmacokinetics of Tenofovir Disoproxil Fumarate and Emtricitabine for On-Demand HIV Preexposure Prophylaxis.

In a randomized, crossover pharmacokinetic study in healthy volunteers (N = 14), a single dose of 2 g probenecid (PRO)-boosted 600 mg tenofovir disoproxil fumarate (TDF)/400 mg emtricitabine (FTC) (test (T) +PRO) was compared with the current on-demand HIV preexposure prophylaxis from the IPERGAY study (a 600 mg TDF/400 mg FTC on day 1 and 300 mg TDF/200 mg FTC on days 2 and 3) (control, C IPERGAY). PRO increased mean single-dose area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞,SD ) of tenofovir (TFV) and FTC by 61% and 68%, respectively. The TFV-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells were higher (~30%) at 24 hours in T +PRO but then fell significantly lower (~40%) at 72 hours compared with C IPERGAY. The interaction between FTC and PRO was unexpected and novel. Further study is needed to determine if this PRO-boosted TDF/FTC regimen would be clinically effective.

Probenecid-Boosted Tenofovir: A Physiologically-Based Pharmacokinetic Model-Informed Strategy for On-Demand HIV Preexposure Prophylaxis.

Multiple doses of tenofovir disoproxil fumarate (TDF) together with emtricitabine is effective for HIV preexposure prophylaxis (PrEP). TDF is converted to tenofovir (TFV) in circulation, which is subsequently cleared via tubular secretion by organic ion transporters (OATs; OAT1 and OAT3). Using in vitro kinetic parameters for TFV and the OAT1 and OAT3 inhibitor probenecid, a bottom-up physiologically-based pharmacokinetic model was successfully developed for the first time that accurately describes the probenecid-TFV interaction. This model predicted an increase in TFV plasma exposure by 60%, which was within 15% of the observed clinical pharmacokinetic data, and a threefold decrease in renal cells exposure following coadministration of a 600 mg TDF dose with 2 g probenecid. When compared with multiple-dose regimens, a single-dose probenecid-boosted TDF regimen may be effective for HIV PrEP and improve adherence and safety by minimizing TFV-induced nephrotoxicity by reducing TFV accumulation in renal cells.

Chemsex is not a barrier to self-reported daily PrEP adherence among PROUD study participants.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a novel HIV prevention method whereby HIV-negative individuals take the drugs tenofovir and emtricitabine to prevent HIV acquisition. Optimal adherence is critical for PrEP efficacy. Chemsex describes sexual activity under the influence of psychoactive drugs, in the UK typically; crystal methamphetamine, gamma-hydroxybutyrate(GHB) and/or mephedrone. Chemsex drug use has been associated with increased HIV transmission risk among gay, bisexual and other men who have sex with men (GBM) and poor ART adherence among people living with HIV. This study assessed whether self-reported chemsex events affected self-reported daily PrEP adherence among PROUD study participants. METHODS: The PROUD study was an open-label, randomised controlled trial, conducted in thirteen English sexual health clinics, assessing effectiveness of TruvadaⓇ-PrEP among 544 HIV-negative GBM. The study reported an 86% risk-reduction of HIV from daily PrEP. Participants were asked about chemsex engagement at follow-up visits. Monthly self-reports of missed PrEP tablets were aggregated to assess adherence between visits. Univariable and multivariable regression analyses were performed to test for associations between chemsex and reporting less than seven out of seven intended doses(<7/7ID) in the 7 days before and/or after last condomless anal intercourse(CAI). RESULTS: 1479 follow-up visit forms and 2260 monthly adherence forms from 388 participants were included in the analyses, with 38.5% visit forms reporting chemsex since last visit and 29.9% follow-up periods reporting <7/7ID. No statistically significant associations were observed between reporting <7/7ID and chemsex (aOR=1.29 [95% CI 0.90-1.87], p = 0.168). Statistically significant associations were seen between reporting <7/7ID and participants perceiving that they would miss PrEP doses during the trial, Asian ethnicity, and reporting unemployment at baseline. CONCLUSIONS: These analyses suggest PrEP remains a feasible and effective HIV prevention method for GBM engaging in chemsex, a practise which is prevalent in this group and has been associated with increased HIV transmission risk.

Low Disclosure of PrEP Nonadherence and HIV-Risk Behaviors Associated With Poor HIV PrEP Adherence in the HPTN 067/ADAPT Study.

OBJECTIVE: We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg. METHODS: Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence. RESULTS: Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(ß) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(ß) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001]. CONCLUSIONS: Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

Review of Real-World Implementation Data on Emtricitabine-Tenofovir Disoproxil Fumarate as HIV Pre-exposure Prophylaxis in the United States.

The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012. Since then, Centers for Disease Control and Prevention guidelines for the use of PrEP have been published and implemented into clinical practice throughout the United States. A number of published open-label and PrEP demonstration projects have evaluated the real-world use of PrEP including analysis of the barriers to its use and addressing major concerns. Despite the approval of FTC/TDF for PrEP, its use for this indication relies on patient and provider acceptance, and its effectiveness requires patient adherence and retention in care during periods of high-risk behaviors. Concerns regarding the use of PrEP in healthy individuals persist and include medication adverse effects including renal dysfunction and bone mineral density loss; risk compensation leading to HIV infections, sexually transmitted infections, and unintended pregnancies; and the development of drug resistance in the event of seroconversion. The cost-effectiveness of PrEP continues to be assessed with the greatest cost-effectiveness remaining in those at highest risk of acquiring HIV. Additionally, cases of HIV acquisition in individuals who are adherent to PrEP highlight scenarios in which PrEP is not 100% effective including against the transmission of drug-resistant HIV strains. This review examines data on the implementation of PrEP outside the setting of clinical trials with the aim of providing clinicians with a summary of the current barriers and opportunities for PrEP use with a specific focus on the role of pharmacists in the optimization of PrEP implementation.

Effect of Vitamin D Supplementation on Bone Turnover Markers During HIV Pre-Exposure Prophylaxis Using Tenofovir Disoproxil Fumarate-Emtricitabine in Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) reduces bone mineral density in HIV-uninfected men who have sex with men (MSM). We hypothesized that PrEP with TDF-FTC would increase bone turnover markers (BTMs) at week 24 and that vitamin D supplementation from weeks 24 to 48 would blunt this increase. Participants were from a cohort of 398 MSM and transgender women who received daily TDF-FTC for PrEP. At week 24, a prospective intervention group initiated vitamin D3 4,000 IU daily. Concurrent controls were selected from the cohort who took ≤400 IU/day of vitamin D3 matched by age, race, and body mass index. The primary endpoint was the change in procollagen-I N-terminal propeptide (P1NP) from weeks 24 to 48. Paired t-tests were used to compare changes in BTMs between intervention and controls. Among 48 intervention-control pairs, median age was 33 years. At baseline, 68.9% of the intervention group and 77.3% of controls were vitamin D sufficient (≥20 ng/mL, p = .94). P1NP, C-telopeptide, parathyroid hormone (PTH), and 25-OH vitamin D3 did not increase significantly at week 24. P1NP fell by a mean ± SD of -27.6 ± 49.9 pg/mL from weeks 24 to 48 with vitamin D and -2.5 ± 40.2 pg/mL in controls (p = .01). There were no significant between-group differences in the weeks 24-48 change in C-telopeptide, PTH, or 25-OH vitamin D3. Vitamin D3 supplementation with 4,000 IU/day resulted in a significant reduction in the BTM P1NP compared with controls, suggesting that this intervention has potential to improve bone health during PrEP.

Renal function and risk factors for renal disease for patients receiving HIV pre-exposure prophylaxis at an inner metropolitan health service.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) significantly reduces the risk of HIV acquisition. TDF is a known nephrotoxin however, renal dysfunction from TDF is mostly reversible following discontinuation. AIMS: To describe the renal function, risk factors for renal disease and associated clinical testing practices in a cohort of PrEP patients. METHODS: A retrospective review was conducted of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney, Australia between April 2016 and July 2017, with follow-up data obtained at 3-monthly intervals until 18 months. RESULTS: 525 patients met inclusion criteria. Patients were almost exclusively male and median age was 34 years (IQR: 28 to 42). At baseline, 1.5% had an estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m2. A small significant drop in eGFR of -2.5 mL/min/1.73m2 (p<0.05) occurred between PrEP commencement and the first follow-up period, followed by a progressive decline in eGFR of -0.38 mL/min/1.73m2 per month (95%CI: -0.57 to -0.20; p<0.001). Renal impairment (eGFR <70 mL/min/1.73m2) occurred in 6.5% of patients and persisted across consecutive follow-up periods in five (1.0%) patients. Patients aged ≥40 years had a greater risk of renal impairment than younger patients (HR 3.9, 95%CI: 1.8 to 8.4; p<0.001), despite similar rates of eGFR decline (p = 0.19). PrEP was discontinued in two patients (0.4%) due to renal function concerns. CONCLUSION: PrEP use led to an initial drop in eGFR and a more gradual progressive decline subsequently, but significant renal impairment remained uncommon up to 18 months of follow-up.

Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: A substudy of the NEAT001/ANRS143 randomised trial.

BACKGROUND: Comparison of changes in body composition, adipokines and inflammatory markers after initial therapy with a nucleos(t)ide reverse transcriptase inhibitor (N(t)RTI)- sparing or containing regimen are scarce. DESIGN: Randomised Clinical Trial. METHODS: This is the body composition substudy of NEAT 001/ANRS 143, a randomised trial comparing darunavir/ritonavir (DRV/r) plus either raltegravir (RAL) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 805 ART naïve HIV-infected adults. The primary endpoint was percentage change in limb fat at week 96. Secondary endpoints were associations among these changes and metabolic markers (IL-6, insulin, leptin, adiponectin, FGF-23). RESULTS: 126 subjects (61 DRV/r + RAL and 65 DRV/r + TDF/FTC) were included. The rate of change in BMI between groups for RAL versus TDF/FTC at week 96 was 1.5% per 48-week period (p = 0.015). The rate of change in limb fat mass, trunk fat mass, total body fat and total lean mass was for RAL versus TDF/FTC at week 96 was 2.5% (p = 0.38), 7.3% ((p = 0.021), 4.9% (p = 0.061) and 1.3% (p = 0.12) respectively. Baseline insulin and leptin levels were correlated with baseline limb fat and trunk fat mass [r = 0.31 (p = 0.0043)/r = 0.28 (p = 0.0011) for limb fat, and r = 0.63 (p<0.0001)/r = 0.50(p<0.0001) for trunk fat]. After adjustment, a 10% faster increase in leptin between baseline and week 48 was associated with a more rapid increase in limb fat at week 48 (0.5% per 48 weeks, p<0.001), total body fat mass (0.6% per 48 weeks, p<0.001), and trunk fat mass (0.3% per 48 weeks, p = 0.0026). CONCLUSIONS: After week 96 a N(t)RTI sparing regimen of DRV/r + RAL produced a numerically greater percentage increase in body composition variables with only change in trunk fat mass and BMI being significant.

Early experience of implementing a national HIV pre-exposure prophylaxis service in Wales, United Kingdom 2017.

Background Pre-exposure prophylaxis (PrEP) was introduced in Sexual Health Services of the Welsh National Health Service (NHS Wales) in July 2017 as a 3-year pilot service. METHODS: Data were collected through the pre-existing Sexual Health in Wales Surveillance System, to which codes were added to capture PrEP eligibility, outcome of offer of PrEP, reasons for declining and adherence. Eligibility categories were defined based on nationally agreed criteria: men who have sex with men (MSM) and transgender people at high risk of HIV acquisition; partners of HIV-positive individuals not known to be virally suppressed; and heterosexuals reporting condomless intercourse with a HIV-positive individual not known to be virally suppressed. RESULTS: During the first 6 months, 516 people were eligible, 96% of which were MSM. Overall, 57% of those eligible (296/516) started PrEP. Reasons for declining PrEP were given by 88 (56%) of 157 people; 50 (57%) of whom did not believe themselves to be at risk. Of the available adherence assessments, 89% considered that all risk episodes had been covered. Persistence at 3 months was assessed for 141 people, of which 93 (66%) were still using PrEP. There were no HIV diagnoses in people taking PrEP during the first 6 months. Twenty-nine people were diagnosed with 37 episodes of sexually transmissible infections (STIs) while on PrEP. STI incidence was 105.7 per 100 person-years. CONCLUSIONS: The early trend indicates that implementation of PrEP is progressing as planned, and the service has been utilised by clients. This analysis can help refine implementation, inform planning and research around uptake, use and effect in Wales and internationally.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out. METHODS: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance. We also collected aggregated data from seven Aids Reference Centres (ARCs) currently providing most of the PrEP care in Belgium. RESULTS: From 1 June 2017 to 28 February 2018, 1352 requests for reimbursement were approved by the National Institute for Health and Disability Insurance. Almost 98% of those who bought at least one box of 30 tablets of emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF) in a Belgian pharmacy were male, and most (67%) were between 30 and 50 years of age. According to data obtained from ARCs, the proportion of those choosing event-driven PrEP initially ranged between 29% and 73%. CONCLUSIONS: The uptake of PrEP in Belgium since the start of the roll-out in June 2017 has been high, and almost entirely limited to men who have sex with men, of whom 43% initially prefer a non-daily regimen. A better understanding is needed as to why other populations, such as sub-Saharan African migrants, are not accessing PrEP, as well as the development of a more sustainable PrEP delivery model.

Maximizing participant retention in a phase 2B HIV prevention trial in Kampala, Uganda: The MTN-003 (VOICE) Study.

BACKGROUND: The success of longitudinal trials depends greatly on using effective strategies to retain participants and ensure internal validity, maintain sufficient statistical power, and provide for the generalizability of study results. OBJECTIVE: This paper describes the challenges and specific strategies used to retain participants in a Phase 2B safety and effectiveness study of daily oral and vaginal tenofovir formulations for the prevention of HIV-1 infection in the MTN-003 (VOICE) trial in Kampala, Uganda. METHODS: Once enrolled, participants were seen every 28 days at the research site and their study product was re-filled. Challenges to retention included a mobile population, non-disclosure of study participation to spouse/family, and economic constraints. Strategies used to maintain high participation rates included the use of detailed locator information, a participant tracking database, regular HIV/STI testing, and the formation of close bonds between staff and subjects. RESULTS: We enrolled 322 women out of the 637 screened. The overall retention rate was 95% over a 3 year follow up period. Only 179 (3%) out of the 6124 expected visits were missed throughout study implementation. Reasons for missed visits included: participants thinking that they did not need frequent visits due to their HIV negative status, time constraints due to commercial sex work, and migration for better employment. CONCLUSIONS: With the implementation of multi-faceted comprehensive follow-up and retention strategies, we achieved very high retention rates in the MTN-003 study. This paper provides a blueprint for effective participant retention strategies for other longitudinal HIV prevention studies in resource-limited settings in Sub-Saharan Africa.

Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790. FINDINGS: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6). INTERPRETATION: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. FUNDING: New South Wales Ministry of Health, Gilead Sciences.