Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

Lessons learnt from daily oral PrEP delivery to inform national planning for PrEP ring introduction for women in low-income and middle-income countries: a qualitative inquiry of international stakeholders.

INTRODUCTION: Some African countries plan to introduce and scale-up new long-acting pre-exposure prophylaxis methods (LA-PrEP), like the monthly dapivirine vaginal ring (PrEP ring) and injectable cabotegravir. National costed implementation plans, roadmaps for successful product implementation, are often overlooked. International stakeholders engaged in oral PrEP planning, introduction and scale-up are an information resource of lessons learned to advise LA-PrEP planning. We consulted such international stakeholders and synthesised oral PrEP lessons to inform the development of a costed rollout plan template for LA-PrEP. METHODS: From selected global health organisations (five international nongovernmental, four donor, four university/research and two multilateral), we interviewed 27 representatives based in America, Europe, Asia and Africa about strategic content and approaches for LA-PrEP policy, programming and implementation. We conducted a thematic analysis of the interview data for implementation considerations. RESULTS: From the consultations, we identified six implementation themes for LA-PrEP introduction and scale-up: (1) ethically increasing choice and avoiding coercion; (2) de-stigmatising PrEP by focusing on preference rather than risk-based eligibility; (3) integrating LA-PrEP into services that are more woman-oriented, couple-oriented and family-oriented, and providing private spaces for LA-PrEP delivery; (4) de-medicalising delivery of relatively safe products (eg, PrEP ring); (5) constructing multilevel, nuanced communication strategies to address measured and perceived product efficacy and effectiveness; and (6) devising product-agnostic, modular approaches to service delivery. Despite the widespread emphasis on integration, few stakeholders offered empirical examples of successful integration approaches and frameworks. CONCLUSIONS: Lessons learnt from stakeholder participants suggest standardised and modular processes can improve efficiencies in LA-PrEP planning and implementation. Tiered communication strategies addressing product efficacy and effectiveness will improve clients' and providers' efficacy in making informed decisions. Integration is important for LA-PrEP delivery, but data on empirical integration approaches and frameworks is minimal: further research in this discipline is needed.

Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study.

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1. METHODS: This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires. RESULTS: Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers. CONCLUSION: Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04006704.

Impact of switching to injectables cabotegravir and rilpivirine on sleep disturbances in a cohort of people living with HIV.

BACKGROUND: Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. METHODS: A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. RESULTS: To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm3, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. CONCLUSIONS: To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Structure-Based Design of Novel Thiazolone[3,2-a]pyrimidine Derivatives as Potent RNase H Inhibitors for HIV Therapy.

Ribonuclease H (RNase H) was identified as an important target for HIV therapy. Currently, no RNase H inhibitors have reached clinical status. Herein, a series of novel thiazolone[3,2-a]pyrimidine-containing RNase H inhibitors were developed, based on the hit compound 10i, identified from screening our in-house compound library. Some of these derivatives exhibited low micromolar inhibitory activity. Among them, compound 12b was identified as the most potent inhibitor of RNase H (IC50 = 2.98 µM). The experiment of magnesium ion coordination was performed to verify that this ligand could coordinate with magnesium ions, indicating its binding ability to the catalytic site of RNase H. Docking studies revealed the main interactions of this ligand with RNase H. A quantitative structure activity relationship (QSAR) was also conducted to disclose several predictive mathematic models. A molecular dynamics simulation was also conducted to determine the stability of the complex. Taken together, thiazolone[3,2-a]pyrimidine can be regarded as a potential scaffold for the further development of RNase H inhibitors.

Need for informed providers: exploring LA-PrEP access in focus groups with PrEP-indicated communities in Baltimore, Maryland.

BACKGROUND: The approval of long-acting pre-exposure prophylaxis PrEP (LA-PrEP) in the United States brings opportunities to overcome barriers of oral PrEP, particularly among sexual and gender minority communities who bear a higher HIV burden. Little is known about real-time decision-making among potential PrEP users of LA-PrEP post-licensure. METHODS: We held focus group discussions with people assigned male at birth who have sex with men in Baltimore, Maryland to explore decision-making, values, and priorities surrounding PrEP usage. A sexual and gender minority-affirming health center that provides PrEP services supported recruitment. Discussions included a pile-sorting activity and were audio-recorded. Recordings were transcribed and analyzed iteratively, combining an inductive and deductive approach. RESULTS: We held five focus groups from Jan-June 2023 with 23 participants (21 cisgender men who have sex with men, two transgender women who have sex with men; mean age 37). Among participants, 21 were on oral PrEP, one was on injectable PrEP, and one had never taken PrEP. Most had never heard about LA-PrEP. When making decisions about PrEP, participants particularly valued efficacy in preventing HIV, side effects, feeling a sense of security, and ease of use. Perceptions varied between whether oral or injectable PrEP was more convenient, but participants valued the new opportunity for a choice in modality. Factors influencing PrEP access included cost, individual awareness, provider awareness, and level of comfort in a healthcare environment. Participants emphasized how few providers are informed about PrEP, placing the burden of being informed about PrEP on them. Comfort and trust in a provider superseded proximity as considerations for if and where to access PrEP. CONCLUSIONS: There is still low awareness about LA-PrEP among sexual and gender minority communities; thus, healthcare providers have a critical role in influencing access to LA-PrEP. Despite this, providers are still vastly underinformed about PrEP and underprepared to support clients in contextualized ways. Clients are more likely to engage in care with affirming providers who offer non-judgmental conversations about sex and life experiences. Provider education in the United States is urgently needed to better support clients in choosing a PrEP modality that is right for them and supporting adherence for effective HIV prevention.

Non-adherence and non-persistence with antiretroviral treatment in Belgium: A real-world evaluation using a pharmacy database, 2018-2021.

PURPOSE: To evaluate the real-world rates of non-adherence and non-persistence to antiretroviral therapy (ART) among treatment-naïve adult patients with HIV after a 12-month follow-up period in Belgium. METHODS: A retrospective analysis of longitudinal pharmacy claims was conducted using the Pharmanet database from January 1, 2018, to December 31, 2021. Non-adherence was assessed over 12 months and reported as the proportion of days covered below the 80% threshold. Non-persistence was defined as the first 90-day gap in treatment between the two types of ART dispensed. Poisson regression with robust standard error and Cox proportional hazard models were used to assess the factors associated with non-adherence and non-persistence, respectively. RESULTS: Overall, 2999 patients were initiated on ART between 2018 and 2021. After a 12-month follow-up, the proportions of non-adherence and non-persistence were 35.6% and 15.9%, respectively in 2018, and decreased to 18.7% and 6.8%, respectively in 2021. Non-adherence was higher among women, Brussels residents, and those receiving multiple-tablet regimens (MTRs). Similarly, the prevalence of non-persistence was higher among women and MTR recipients. CONCLUSION: Among treatment-naïve adults with HIV in Belgium, non-adherence, and non-persistence to ART showed improvement over the study period but remained at high levels. Disparities were observed by sex and between geographical regions. Prioritizing strategies targeting women in Brussels and facilitating the transition from MTRs to single-tablet regimens should be emphasized optimize adherence to ART in Belgium.

Urine tenofovir testing for real-time PrEP adherence feedback: a qualitative study involving transgender women in Uganda.

INTRODUCTION: Adherence counselling with point-of-care (POC) drug-level feedback using a novel tenofovir assay may support pre-exposure prophylaxis (PrEP) adherence; however, perceptions of urine testing and its impact on adherence are not well studied. We qualitatively examined how POC tenofovir testing was experienced by transgender women (TGW) in Uganda. METHODS: Within a cluster randomized trial of peer-delivered HIV self-testing, self-sampling for sexually transmitted infections and PrEP among HIV-negative TGW showing overall low PrEP prevention-effective adherence (NCT04328025), we conducted a nested qualitative sub-study of the urine POC assay among a random sample of 30 TGW (August 2021-February 2022). TGW interviews explored: (1) experiences with POC urine tenofovir testing and (2) perceptions of PrEP adherence counselling with drug-level feedback. We used an inductive content analytic approach for analysis. RESULTS: Median age was 21 years (interquartile range 20-24), and 70% engaged in sex work. Four content categories describe how TGW experienced POC urine tenofovir testing: (1) Urine tenofovir testing was initially met with scepticism: Testing urine to detect PrEP initially induced anxiety, with some perceptions of being intrusive and unwarranted. With counselling, however, participants found POC testing acceptable and beneficial. (2) Alignment of urine test results and adherence behaviours: Drug-level feedback aligned with what TGW knew about their adherence. Concurrence between pill taking and tenofovir detection in urine reinforced confidence in test accuracy. (3) Interpretation of urine tenofovir results: TGW familiar with the interpretation of oral-fluid HIV self-tests knew that two lines on the test device signified positivity (presence of HIV). However, two lines on the urine test strip indicated a positive result for non-adherence (absence of tenofovir), causing confusion. Research nurses explained the difference in test interpretation to participants' satisfaction. (4) White coat dosing: Some TGW deliberately chose not to attend scheduled clinic appointments to avoid detecting their PrEP non-adherence during urine testing. They restarted PrEP before returning to clinic, a behaviour called "white coat dosing." CONCLUSIONS: Incorporating POC urine testing into routine PrEP adherence counselling was acceptable and potentially beneficial for TGW but required attention to context. Additional research is needed to identify effective strategies for optimizing adherence monitoring and counselling for this population.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Low selection of HIV PrEP refills at private pharmacies among clients who initiated PrEP at public clinics: findings from a mixed-methods study in Kenya.

BACKGROUND: In Africa, the delivery of HIV pre-exposure prophylaxis (PrEP) at public healthcare clinics is challenged by understaffing, overcrowding, and HIV-associated stigma, often resulting in low PrEP uptake and continuation among clients. Giving clients the option to refill PrEP at nearby private pharmacies, which are often more convenient and have shorter wait times, may address these challenges and improve PrEP continuation. METHODS: This mixed methods study used an explanatory sequential design. At two public clinics in Kiambu County, Kenya, clients ≥ 18 years initiating PrEP were given the option to refill PrEP at the clinic where they initiated for free or at one of three nearby private pharmacies for 300 Kenyan Shillings (~ $3 US Dollars). The providers at these pharmacies (pharmacists and pharmaceutical technologists) were trained in PrEP service delivery using a prescribing checklist and provider-assisted HIV self-testing, both with remote clinician oversight. Clients were followed up to seven months, with scheduled refill visits at one, four, and seven months. The primary outcomes were selection of pharmacy-based PrEP refills and PrEP continuation. Following pilot completion, 15 in-depth interviews (IDIs) with clients who refilled PrEP were completed. We used descriptive statistics and thematic analysis to assess study outcomes. RESULTS: From November 2020 to November 2021, 125 PrEP clients were screened and 106 enrolled. The majority (59%, 63/106) of clients were women and the median age was 31 years (IQR 26-38 years). Over 292 client-months of follow-up, 41 clients (39%) refilled PrEP; only three (3%) at a participating pharmacy. All clients who completed IDIs refilled PrEP at clinics. The reasons why clients did not refill PrEP at pharmacies included: a preference for clinic-delivered PrEP services (i.e., pre-existing relationships, access to other services), concerns about pharmacy-delivered PrEP services (i.e., mistrust, lower quality care, costs), and lack of knowledge of this refill location. CONCLUSIONS: These findings suggest that clients who initiate PrEP at public clinics in Kenya may have already overcome barriers to clinic-delivered PrEP services and prefer PrEP access there. To reach new populations that could benefit from PrEP, a stand-alone model of pharmacy-delivered PrEP services may be needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04558554 [registered: June 5, 2020].

Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia. METHODS: A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I2 statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed. RESULTS: Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]). CONCLUSIONS: This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.

Porphyrins with combinations of 4-carboxyphenyl and 4-hydroxyphenyl substituents in meso-positions as anti-HIV-1 agents.

A series of 4-carboxyphenyl/4-hydroxyphenyl meso-substituted porphyrins were synthesized, purified, and characterized. The compounds exhibited anti-HIV-1 activities, in vitro, under both non-photodynamic (non-PDT) and photodynamic (PDT) conditions. Specifically, the porphyrins inhibited HIV-1 virus entry, with c-PB2(OH)2 and PB(OH)3 showing significant anti-HIV-1 activity. All of the porphyrins inhibited HIV-1 subtype B and C virus entry under PDT conditions. Our study demonstrated that the compounds bearing combinations of 4-carboxyphenyl/4-hydroxyphenyl moieties were not toxic even at higher concentrations, as compared to the reference porphyrins 5,10,15,20-tetra-(4-carboxyphenyl)porphyrin (TCPP) and 5,10,15,20-tetra-(4-hydroxyphenyl)porphyrin (THPP), under PDT conditions. This study underscores the promising potential of these compounds as HIV entry inhibitors in both non-PDT and PDT scenarios.

Reducing time to differentiated service delivery for newly-diagnosed people living with HIV in Kigali, Rwanda: a pilot, unblinded, randomized controlled trial.

BACKGROUND: Differentiated service delivery (DSD) programs for people living with HIV (PWH) limit eligibility to patients established on antiretroviral therapy (ART), yet uncertainty exists regarding the duration on ART necessary for newly-diagnosed PWH to be considered established. We aimed to determine the feasibility, acceptability, and preliminary impact of entry into DSD at six months after ART initiation for newly-diagnosed PWH. METHODS: We conducted a pilot randomized controlled trial in three health facilities in Rwanda. Participants were randomized to: (1) entry into DSD at six months after ART initiation after one suppressed viral load (DSD-1VL); (2) entry into DSD at six months after ART initiation after two consecutive suppressed viral loads (DSD-2VL); (3) treatment as usual (TAU). We examined feasibility by examining the proportion of participants assigned to intervention arms who entered DSD, assessed acceptability through patient surveys and by examining instances when clinical staff overrode the study assignment, and evaluated preliminary effectiveness by comparing study arms with respect to 12-month viral suppression. RESULTS: Among 90 participants, 31 were randomized to DSD-1VL, 31 to DSD-2VL, and 28 to TAU. Among 62 participants randomized to DSD-1VL or DSD-2VL, 37 (60%) entered DSD at 6 months while 21 (34%) did not enter DSD because they were not virally suppressed. Patient-level acceptability was high for both clinical (mean score: 3.8 out of 5) and non-clinical (mean score: 4.1) elements of care and did not differ significantly across study arms. Viral suppression at 12 months was 81%, 81% and 68% in DSD-1VL, DSD-2VL, and TAU, respectively (p = 0.41). CONCLUSIONS: The majority of participants randomized to intervention arms entered DSD and had similar rates of viral suppression compared to TAU. Results suggest that early DSD at six months after ART initiation is feasible for newly-diagnosed PWH, and support current WHO guidelines on DSD. TRIAL REGISTRATION: Clinicaltrials.gov NCT04567693; first registered on September 28, 2020.

Exploring adolescent girls and young women's PrEP-user profiles: qualitative insights into differentiated PrEP delivery platform selection and engagement in Cape Town, South Africa.

INTRODUCTION: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre-exposure prophylaxis (PrEP). With ongoing PrEP scale-up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. METHODS: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16-25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community-based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light-touch PrEP refill services incorporating rapid HIV self-testing. We conducted in-depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP-use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision-making and habits related to PrEP access to inform market segmentation. RESULTS: We interviewed 26 AGYW (median age 20) PrEP-users between November 2020 and March 2021. AGYW PrEP-users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP-user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent-friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP-user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception-PrEP refill visits (mobile and government clinic). The "Independent PrEP-user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP-user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self-testing had minimal influence on PrEP delivery choice. CONCLUSIONS: Market segmentation of AGYW characterizes different types of PrEP-users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits.

Experiences of oral pre-exposure prophylaxis use among heterosexual men accessing sexual and reproductive health services in South Africa: a qualitative study.

INTRODUCTION: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS-related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre-exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. METHODS: This study forms part of a mixed-methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in-depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. RESULTS: The final analysis included 28 heterosexual men (18-56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self-perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily-pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. CONCLUSIONS: Our study reports on the experiences of heterosexual men accessing oral PrEP in real-world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access.

Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.

Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19th October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I2 = 100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I2 = 94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.

Viral load suppression and its predictor among HIV seropositive people who receive enhanced adherence counseling at public health institutions in Bahir Dar, Northwest Ethiopia. Retrospective follow-up study.

BACKGROUND: For those HIV seropositive people with high viral loads, the World Health Organization recommends more counseling before changing ART regimens. A high viral load can lead to increased HIV transmission and lower survival rates. Clients with viral loads above 1000 copies/mL should receive enhanced adherence counseling for 3-6 months before switching. Despite enhanced adherence counseling programs, most countries struggle with viral load suppression. Little is known about viral load suppression in Ethiopia and the research area after counseling. OBJECTIVE: This study aims to assess viral load suppression and its predictors among HIV-positive individuals receiving enhanced adherence counseling in Bahir Dar, Northwest Ethiopia, in 2022. METHODS: An institution-based retrospective follow-up study was conducted among randomly selected 546 clients on Enhanced Adherence Counseling at public health facilities in Bahir Dar city. The Epicollect5 mobile application was used to collect the data, which was then exported to Stata version 14 for analysis. A Log-Binomial regression model was fitted for each explanatory variable. Variables having a p-value <0.25 in bivariate analysis were entered into a multivariable Log-Binomial regression model. Finally, an adjusted risk ratio with a 95% confidence interval and a p-value <0.05 was used to measure the strength of the prediction. RESULTS: Following enhanced adherence counseling, 312 (57.1%) people had their viral load suppressed. Absence of recurrent OI (ARR 1.40; CI 1.03-1.91), EAC stay less than 3 months (ARR 1.54; CI 1.19-1.99), EAC stay 3-6 months (ARR 1.38; CI 1.12-1.69), once-daily ARV dose regimen (ARR 1.28; CI 1.03-1.58), baseline viral load of 2879.00 copies/ml (ARR 1.30, CI 1.06-1.60), being orthodox Tewahido Christian (ARR 0.37; CI 0.18-0.75) were significant predictors of viral load suppression after Enhanced Adherence Counseling. CONCLUSION AND RECOMMENDATION: Most importantly, this study found that most people had suppressed viral loads after receiving enhanced adherence counseling. Significant predictors of viral load suppression included recurrent OI, length of stay on EAC, daily ARV dosing regimen, baseline viral load, and religion. Clients with a high baseline viral load and those who experience recurring opportunistic infections should get extra care during EAC sessions.