Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide.

Two HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with highly potent, long-acting antiviral activity. Monotherapy using a low dose of LP-98 sharply reduced viral loads and maintained long-term viral suppression in 21 SHIVSF162P3-infected rhesus macaques. We found that five treated monkeys achieved potential posttreatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, whereas monkeys with a stable viral rebound had higher viral DNA in superficial lymph nodes. The tissues of PTC monkeys exhibited significantly decreased quantitative viral outgrowth and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells contributed to virologic control efficacy. Moreover, LP-98 administrated as a pre-exposure prophylaxis (PrEP) provided complete protection against SHIVSF162P3 and SIVmac239 infections in 51 monkeys via intrarectal, intravaginal, or intravenous challenge. In conclusion, our lipopeptides exhibit high potential as an efficient HIV treatment or prevention strategy.

HIV Prevention Among Men Who Have Sex With Men: Tenofovir Alafenamide Combination Preexposure Prophylaxis Versus Placebo.

BACKGROUND: While noninferiority of tenofovir alafenamide and emtricitabine (TAF/FTC) as preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has been shown, interest remains in its efficacy relative to placebo. We estimate the efficacy of TAF/FTC PrEP versus placebo for the prevention of HIV infection. METHODS: We used data from the DISCOVER and iPrEx trials to compare TAF/FTC to placebo. DISCOVER was a noninferiority trial conducted from 2016 to 2017. iPrEx was a placebo-controlled trial conducted from 2007 to 2009. Inverse probability weights were used to standardize the iPrEx participants to the distribution of demographics and risk factors in the DISCOVER trial. To check the comparison, we evaluated whether risk of HIV infection in the shared tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) arms was similar. RESULTS: Notable differences in demographics and risk factors occurred between trials. After standardization, the difference in risk of HIV infection between the TDF/FTC arms was near zero. The risk of HIV with TAF/FTC was 5.8 percentage points lower (95% confidence interval [CI], -2.0% to -9.6%) or 12.5-fold lower (95% CI, .02 to .31) than placebo standardized to the DISCOVER population. CONCLUSIONS: There was a reduction in HIV infection with TAF/FTC versus placebo across 96 weeks of follow-up. CLINICAL TRIALS REGISTRATION: NCT02842086 and NCT00458393.

Drug concentrations in hair and dried blood spots as PrEP adherence metrics during pregnancy and postpartum.

We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV pre-exposure prophylaxis (PrEP) during pregnancy and postpartum and compared hair levels with tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). Overall, 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster randomized trial. Having a partner known to be living with HIV was associated with higher hair TFV levels (p<0.001). Hair TFV concentrations were strongly correlated with DBS TFV-DP levels (r=0.76, p<0.001), indicating hair as promising cumulative adherence metric for perinatal PrEP assessment.

Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques.

Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.

Differential Laminar Activation Dissociates Encoding and Retrieval in the Human Medial and Lateral Entorhinal Cortex.

The hierarchically organized structures of the medial temporal lobe are critically important for episodic memory function. Accumulating evidence suggests dissociable information processing pathways are maintained throughout these structures including in the medial and lateral entorhinal cortex. Cortical layers provide an additional dimension of dissociation as the primary input to the hippocampus derives from layer 2 neurons in the entorhinal cortex, whereas the deeper layers primarily receive output from the hippocampus. Here, novel high-resolution T2-prepared functional MRI methods were successfully used to mitigate susceptibility artifacts typically affecting MRI signals in this region providing uniform sensitivity across the medial and lateral entorhinal cortex. During the performance of a memory task, healthy human subjects (age 25-33 years, mean age 28.2 ± 3.3 years, 4 female) showed differential functional activation in the superficial and deep layers of the entorhinal cortex associated with task-related encoding and retrieval conditions, respectively. The methods provided here offer an approach to probe layer-specific activation in normal cognition and conditions contributing to memory impairment.SIGNIFICANCE STATEMENT This study provides new evidence for differential neuronal activation in the superficial versus deep layers of the entorhinal cortex associated with encoding and retrieval memory processes, respectively, in cognitively normal adults. The study further shows that this dissociation can be observed in both the medial and the lateral entorhinal cortex. The study was achieved by using a novel functional MRI method allowing us to measure robust functional MRI signals in both the medial and lateral entorhinal cortex that was not possible in previous studies. The methodology established here in healthy human subjects lays a solid foundation for subsequent studies investigating layer-specific and region-specific changes in the entorhinal cortex associated with memory impairment in various conditions such as Alzheimer's disease.

Global HIV Incidence Analysis and Implications for Affordability Using Long-Acting Cabotegravir Versus Continuous and Event-Driven Oral Preexposure Prophylaxis.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC. METHODS: A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy. RESULTS: Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923). CONCLUSIONS: High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets.

Antiretrovirals and Weight Change: Weighing the Evidence.

Body weight is influenced by an interplay of individual and environmental factors. In people with HIV (PWH), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy (ART). Weight changes in comparative ART trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors (INSTIs) dolutegravir and bictegravir, particularly when co-administered with tenofovir alafenamide fumarate (TAF), compared to regimens that include agents such as tenofovir disoproxil fumarate (TDF) that attenuate weight gain. We review weight changes in major randomized trials of pre-exposure prophylaxis (PrEP) and initial and switch HIV therapy, highlighting the challenges to assessing the role of ART in weight change. This examination forms the basis for a model that questions assumptions regarding an association between INSTI and TAF and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions.

STI/HIV testing, STIs, and HIV PrEP use among men who have sex with men (MSM) and men who have sex with men and women (MSMW) in United States, 2019-2022.

BACKGROUND: Routine sexually transmitted infection and human immunodeficiency virus (STI/HIV) testing and HIV pre-exposure prophylaxis (PrEP) use are recommended for men who have sex with men (MSM) at increased risk of HIV. METHODS: Using Healthverity, a large administrative dataset in the United States, we assessed STI/HIV testing, chlamydia and gonorrhea positivity by specimen type, and HIV PrEP use among MSM and men who have sex with men and women (MSMW) at their first visits (index date) for those at increased risk of HIV and STIs from 2019 through 2022. RESULTS: Among 81,716 MSM and MSMW aged 15-64 years at their index date visit, STI testing rates were 57.9% for chlamydia, 58.1% for gonorrhea, and 52.2% for syphilis testing, respectively; 55.5%, 30.9%, and 18.1% had HIV testing, HIV PrEP use, and PrEP initiation, respectively, among the patients who did not have HIV. Of patients with chlamydia and gonorrhea testing, 48% were tested from the genital site only and 25% from three anatomic sites (rectal, pharyngeal, and urogenital). Chlamydia and gonorrhea positivity was 9.8% for chlamydia rectal infection, 7.3% for gonorrhea rectal infection, and 5.3% for gonorrhea pharyngeal infection. CONCLUSION: Our results present current medical services provided during initial clinic visits for MSM and MSMW in private outpatient settings. Our study suggests that the assessment of STI/HIV testing is periodically needed due to the high prevalence of infection, and efforts to promote HIV PrEP for MSM and MSMW in private settings are urgently needed.

HIV Risk and Interest in Preexposure Prophylaxis in Justice-Involved Persons.

Preexposure prophylaxis (PrEP) is underused in persons who use drugs and justice-involved persons. In an ongoing randomized controlled trial in 4 US locations comparing patient navigation versus mobile health unit on time to initiation of HIV medication or PrEP for justice-involved persons who use stimulants or opioids and who are at risk for or living with HIV, we assessed HIV risk factors, perceived HIV risk, and interest in PrEP. Participants without HIV (n = 195) were 77% men, 65% White, 23% Black, and 26% Hispanic; 73% reported a recent history of condomless sex, mainly with partners of unknown HIV status. Of 34% (67/195) reporting injection drug use, 43% reported sharing equipment. Despite risk factors, many persons reported their risk for acquiring HIV as low (47%) or no (43%) risk, although 51/93 (55%) with PrEP indications reported interest in PrEP. Justice-involved persons who use drugs underestimated their HIV risk and might benefit from increased PrEP education efforts.

Cascade analysis of awareness, willingness, uptake and adherence with regard to PrEP among young men who have sex with men (YMSM) in China: A comparison between students and non-students.

INTRODUCTION: In China, young men who have sex with men (YMSM) are one of the groups most at risk of HIV/AIDS. The uptake of pre-exposure prophylaxis (PrEP) among YMSM has not been well documented. A cascade analysis of awareness, willingness, use and adherence with regard to PrEP was conducted separately among YMSM students and non-students. METHODS: From 20 October to 30 December 2021, all adolescents aged 16-24 years were selected for the study from among MSM recruited from 31 provincial administrative regions in mainland China. Participants were included in a cross-sectional study of awareness, willingness, use and adherence with regard to PrEP among YMSM. Logistic regression modelling was used to identify factors associated with the four outcomes. RESULTS: Among 1014 student and 866 non-student YMSMs, respectively, 88.07% and 81.64% had heard of PrEP; 58.16% and 50.35% were willing to use PrEP; 7.59% and 7.62% had used PrEP; and 3.16% and 3.58% had adhered to PrEP. Among students, those living in high-risk areas and pilot cities and those who had engaged in commercial sex and group sex had a positive effect on PrEP use, and the same trends were found among non-students living in high-risk areas and pilot cities and those who had engaged in group sex. 'Daily oral' and 'flexible' PrEP use positively influenced adherence among both groups. CONCLUSIONS: A differentiation strategy of PrEP promotion should be implemented among YMSM. Material support for students, such as financial resources, should increase, while non-students should increase their level of perception of HIV risk.

HIV pre-exposure prophylaxis services, provision, and delivery in the European treatment network of HIV, hepatitis and global emerging infectious diseases (NEAT ID).

OBJECTIVES: We conducted a survey to evaluate HIV pre-exposure prophylaxis (PrEP) practices in a European clinical research network on HIV, hepatitis, and global infectious diseases (NEAT ID). METHODS: An online survey comprising 22 questions was sent via a secure electronic tool to the investigating physician of each of the 342 NEAT ID study centres across 15 European countries in November 2020. RESULTS: In total, 50 sites from 12 countries responded (15% response rate). Most sites were in Western Europe, two were in Poland, and one was in Hungary. Of the responding sites, 45 provided PrEP services for a total of 27 416 PrEP users, with 1361 new PrEP initiators each month. These centres supplied PrEP for men who have sex with men (100%), people who inject drugs (84%), sex workers (84%), women (62%), and transgender women (31%). PrEP persistence after 1 year was >90%, 75%-90%, and 40%-75% in 17, 24, and 4 centres, respectively. In total, 32/45 (71%) centres reported strong community-based organization commitment at their site, and 15/45 (33%) centres developed task-shifting processes to deliver PrEP through nurses (11/15), pharmacists (5/15), and key-population peers (2/15). The biggest barriers to implementation of PrEP were low awareness of and knowledge about PrEP (47%), unwillingness to disclose sexual identity or at-risk behaviour (36%), and lack of administrative support (29%). Of the 45 centres, 32 (71%) have already been involved in PrEP research and 43 (96%) were interested in participating in such studies. CONCLUSIONS: The few NEAT ID centres that responded to the survey showed disparities in PrEP deployment and practices despite a common interest in participating in research in this field.

Scars are frequently found as late sequelae in individuals affected by the 2022 mpox outbreak.

BACKGROUND: The 2022 mpox outbreak continues, and while progress has been made in prevention strategies and potential treatment options, data on late sequelae following mpox are scarce. OBJECTIVE: This analysis aimed to assess the incidence of scar formation in individuals affected by the 2022 mpox outbreak. METHODS: All individuals diagnosed with mpox at the Department of Dermatology at the Medical University of Vienna in 2022 were included in this analysis. Follow-up data were collected throughout November 2023. 'Scar formation' was defined as having at least one scar at the former active mpox lesions. RESULTS: At our clinic, 28 cases of mpox presented between June 2022 and October 2022 and exclusively occurred in men who have sex with men (100%, 28/28), of whom 46% (13/28) were living with HIV, and 32% (9/28) were using pre-exposure prophylaxis (PrEP). Secondary bacterial infection of mpox lesions was suspected in six individuals, and all received systemic antibiotics. Overall, 26 were followed up in November 2023 after a median time of 15 months, and scar formations were found in 43% of cases. CONCLUSIONS: Our data provide insights into the late yet cumulating disease burden caused by the 2022 mpox outbreak. Highly effective prevention strategies are warranted to overcome the mpox epidemic and its potential late sequelae.

Nanopore sequencing of forensic short tandem repeats using QNome of Qitan Technology.

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

Markedly increased duodenal villous surface apoptosis in patients taking pre-exposure prophylaxis (PrEP) against human immunodeficiency virus.

AIMS: Pre-exposure prophylaxis (PrEP) consists of combination antiretroviral therapy and is increasingly utilized to prevent human immunodeficiency virus (HIV) in high-risk populations. Two index cases noted during routine care showed markedly increased duodenal villous surface apoptosis in patients on PrEP. We sought to examine the prevalence of this finding and identify any clinicopathologic correlations. METHODS: Gastrointestinal biopsy specimens from 23 male patients aged 18-40 years taking PrEP and 23 control patients were reviewed. Patients with HIV, inflammatory gastrointestinal diseases, and celiac disease were excluded. Apoptoses were counted on surface epithelium and deep crypts. The highest apoptotic body count per tissue fragment was recorded. Clusters were defined as groups of ≥5 apoptoses. Apoptotic counts between patients taking PrEP and controls were compared using t-tests. RESULTS: In PrEP patients, the median age was 35 years (range 25-40) and 83% (19/23) were white. The control patients were demographically similar (median age: 32 years [range 23-40]; 70% [16/23] white). Duodenal apoptosis in villous surface epithelium was increased in PrEP patients, with 14/23 (60.9%) patients having ≥10 surface apoptoses compared to 2/23 (8.7%) controls (P = 2.1 × 10-3 ) and 14/23 (61%) having clusters compared to 3/23 (13%) controls (P = 2.0 × 10-3 ). There was no significant association between increased surface apoptosis or clusters and clinical symptoms or duration of PrEP use. CONCLUSION: Markedly increased villous surface apoptosis, particularly in clusters, is often seen in the duodenum of patients taking PrEP. Although the mechanism and significance are unknown, knowledge of this peculiar finding may prevent unnecessary additional testing.

Frequent chlamydia and gonorrhoea but very infrequent syphilis among men who have sex with men using HIV pre-exposure prophylaxis in West Africa.

OBJECTIVES: Although oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence and determinants of bacterial STIs in men who have sex with men (MSM) taking PrEP in Burkina Faso, Côte d'Ivoire, Mali and Togo. METHODS: A prospective cohort study among MSM initiating PrEP as part of a comprehensive HIV prevention package was conducted between 2017 and 2021 in community-based clinics in the four study countries. Molecular screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was performed at months 0, 6 and 12. Serological testing for syphilis was performed every 3 months over the first year of follow-up. Determinants of CT and/or NG incidence were identified using Poisson generalised linear mixed models. RESULTS: A total of 598 participants with a median age of 24.7 years were included. Prevalence of CT and/or NG was 24.4% (95% CI 21.0 to 28.1), 22.4% (95% CI 18.4 to 26.8) and 29.0% (95% CI 24.2 to 34.1) at months 0, 6 and 12, respectively. The prevalence of syphilis ranged from 0.2% (95% CI 0.0 to 0.9) at month 0 to 0.8% (95% CI 0.2 to 2.4) at month 12. Ninety incident CT and/or NG infections occurred during a total follow-up time of 280.6 person-years (incidence rate 32.1 per 100 person-years, 95% CI 25.8 to 39.4). Three incident syphilis infections were detected during a total follow-up time of 459.7 person-years (incidence rate 0.7 per 100 person-years, 95% CI 0.1 to 1.9). CT and/or NG incidence was associated with condomless insertive anal sex (adjusted incidence rate ratio 1.96, 95% CI 1.04 to 3.71, p=0.038). CONCLUSIONS: CT and NG were frequent but syphilis was very infrequent in MSM using HIV PrEP in West Africa. HIV programme managers should integrate STI services into PrEP programmes.

The Characterization of Multifaceted PREP1 Peptides Provides Insights into Correlations between Spectroscopic and Structural Properties of Amyloid-like Assemblies.

The widespread ability of proteins and peptides to self-assemble by forming cross-ß structure is one of the most significant discoveries in structural biology. Intriguingly, the cross-ß association of proteins/peptides may generate intricate supramolecular architectures with uncommon spectroscopic properties. We have recently characterized self-assembled peptides extracted from the PREP1 protein that are endowed with interesting structural/spectroscopic properties. We here demonstrate that the green fluorescence emission of the peptide PREP1[117-132] (λem ~520 nm), can be induced by excitation with UV radiation. The associated unusually large Stokes shift (Δλ ~150 nm) represents, to the best of our knowledge, the first evidence of an internal resonance energy transfer in amyloid-like structures, where the blue emission of some assemblies becomes the excitation radiation for others. Moreover, the characterization of PREP1[117-132] variants provides insights into the sequence/structure and structure/spectroscopic properties relationships. Our data suggests that the green fluorescence is plausibly associated with antiparallel ß-sheet states of the peptide whereas parallel ß-sheet assemblies are only endowed with blue fluorescence. Notably, the different PREP1[117-132] variants also form assemblies characterized by distinct morphologies. Indeed, the parent peptide and single mutants form compact but structured aggregates whereas most of the double mutants exhibit elongated and highly extended fibers.

Presequence protease reverses mitochondria-specific amyloid-ß-induced mitophagy to protect mitochondria.

Amyloid-ß (Aß) peptide is accumulated in the mitochondria and has been shown to play a central role in the development of Alzheimer's disease (AD). It has been shown that exposure of neurons to aggregated Aß can result in damaged mitochondria and dysregulated mitophagy, indicating that changes in the Aß content of mitochondria may affect the levels of mitophagy and interfere with the progression of AD. However, the direct influence of mitochondrial Aß on mitophagy has not been elucidated. In the present study, the effect of the mitochondria-specific Aß was assessed following a direct change of Aß content in the mitochondria. We directly change mitochondrial Aß by transfecting cells with mitochondria-associated plasmids, including the mitochondrial outer membrane protein translocase 22 (TOMM22) and 40 (TOMM40) or presequence protease (PreP) overexpression plasmids. The changes in the levels of mitophagy were assessed by TEM, Western blot, mito-Keima construct, organelle tracker, and probe JC-1 assay. We demonstrated that increased mitochondrial Aß content enhance mitophagy levels; overexpression of PreP could reverse the mitochondrial Aß-induced mitophagy levels in vivo and in vitro by reversing the levels of reactive oxygen species (ROS) and the mitochondrial membrane potential. The data provide novel insight into the role of mitochondria-specific Aß in the progression of AD pathophysiology.

The impact of blood donation deferral strategies on the eligibility of men who have sex with men and other sexual risk behavior in Australia.

BACKGROUND: In Australia, a man cannot donate blood if he has had sex with another man within the past 3 months. However, this policy has been criticized as being discriminatory as it does not consider lower risk subgroups, and led to calls for modifications to the policy that more accurately distinguish risk among gay, bisexual, and other men who have sex with men (GBM). STUDY DESIGN AND METHODS: We used data from a nationally representative survey to estimate the proportion of GBM aged 18-74 years old who would be eligible to donate under current criteria and other scenarios. RESULTS: Among the 5178 survey participants, 155 (3.0%) were classified as GBM based on survey responses, Among the GBM, 40.2% (95% CI 28.0%-53.7%) were eligible to donate based on current criteria, and 21.0% (95% CI 14.5%-29.5%) were ineligible due to the 3 months deferral alone. Eligibility among GBM, all men, and the population increased as criteria were removed. Under the new Australian plasma donation criteria, 73.6% (95% CI 64.4%-81.1%) of GBM, 68.4% (95% CI 65.5%-71.2%) of all men, and 60.8% (95% CI 58.8%-62.8%) of the full population were estimated to be eligible. Only 16.1% (95% CI 8.6%-28.1%) of GBM knew that the male-to-male sex deferral period is 3 months. DISCUSSION: Changing the deferral criteria and sexual risk evaluation would lead to a higher proportion of GBM being eligible to donate blood. Knowledge of the current GBM deferral period is very low. Improved education about the current criteria and any future changes are required to improve blood donation rates.

Cost of implementing HIV pre-exposure prophylaxis at community-based clinics in Indonesia.

INTRODUCTION: Currently, Indonesia still has one of the highest rates of new HIV/AIDS infections among countries in Asia and the Pacific region. The WHO has recommended pre-exposure prophylaxis (PrEP) as an additional HIV epidemic prevention step, which has been applied globally and related to the reduction in the number of HIV cases. However, information on the cost of implementing PrEP is rarely available in developing countries, especially in Southeast Asia. Designing a cost-effective approach to scale up PrEP and to estimate the potential budget impact requires information on the cost of implementing PrEP. This study aims to estimate the cost of implementing PrEP at community-based clinics in Indonesia. METHODS: We collected healthcare and non-healthcare/client costs from nine community-based clinics in various cities/districts in Indonesia. The healthcare costs included data on resource utilisation and costs to deliver PrEP, divided into recurrent and capital costs using a discount rate of 3%. Non-healthcare costs included out-of-pocket costs (e.g., transportation, meals) and productivity loss by clients and accompanying person(s) in accessing PrEP. On average, we interviewed 27 clients/clinic. RESULTS: The annual cost of providing PrEP per client is US $365.03, 39% lower than the yearly cost of antiretroviral treatment (ART) per person (approximately US $600). Drugs and non-healthcare costs contribute approximately 67% of the cost. The cost of PrEP amounts to US $292,756.45/year, covering 802 clients. The non-healthcare cost per visit at all sites never reaches more than 10% of the average monthly household expenditure. CONCLUSIONS: The cost of providing PrEP per person is approximately US $365 and is 39% lower than the annual cost of ART per person. Lowering the cost of PrEP ARV drugs would reduce the cost. Scaling up PrEP should recognise this cost structure and strive to reach economies of scale as the intervention gains more clients while simultaneously controlling new HIV infections.

Getting HIV Pre-exposure Prophylaxis (PrEP) into Private Pharmacies: Global Delivery Models and Research Directions.

PURPOSE OF REVIEW: To provide an overview of the current state of HIV pre-exposure prophylaxis (PrEP) delivery via private sector pharmacies globally, to discuss the context-specific factors that have influenced the design and implementation of different pharmacy-based PrEP delivery models in three example settings, and to identify future research directions. RECENT FINDINGS: Multiple high- and low-income countries are implementing or pilot testing PrEP delivery via private pharmacies using a variety of delivery models, tailored to the context. Current evidence indicates that pharmacy-based PrEP services are in demand and generally acceptable to clients and pharmacy providers. Additionally, the evidence suggests that with proper training and oversight, pharmacy providers are capable of safely initiating and managing clients on PrEP. The delivery of PrEP services at private pharmacies also achieves similar levels of PrEP initiation and continuation as traditional health clinics, but additionally reach individuals underserved by such clinics (e.g., young men; minorities), making pharmacies well-positioned to increase overall PrEP coverage. Implementation of pharmacy-based PrEP services will look different in each context and depend not only on the state of the private pharmacy sector, but also on the extent to which key needs related to governance, financing, and regulation are addressed. Private pharmacies are a promising delivery channel for PrEP in diverse settings. Countries with robust private pharmacy sectors and populations at HIV risk should focus on aligning key areas related to governance, financing, and regulation that have proven critical to pharmacy-based PrEP delivery while pursuing an ambitious research agenda to generate information for decision-making. Additionally, the nascency of pharmacy-based PrEP delivery in both high- and low-and-middle-income settings presents a prime opportunity for shared learning and innovation.