Preexposure prophylaxis for preventing HIV infection: Routine practice in primary care.

An estimated 1.2 million people in the United States have human immunodeficiency virus (HIV) infection per US Centers for Disease Control and Prevention 2021 data. The highest risk of HIV transmission occurs during injection drug use with needle sharing and during sexual activity, most significantly in condomless, receptive anal intercourse. Preexposure prophylaxis (PrEP) for the prevention of HIV infection is part of a larger biobehavioral strategy that uses antiretroviral medication, an oral formulation taken daily or during anticipated exposure events, or an injectable formulation administered every 8 weeks. PrEP consists of 3 possible regimens: emtricitabine/tenofovir disoproxil fumarate, emtricitabine/tenofovir alafenamide, or injectable cabotegravir. Primary care clinicians are strategically positioned to provide PrEP education and access.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

PrEP facilitators and barriers in substance use bridge clinics for women who engage in sex work and who use drugs.

BACKGROUND: Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings. METHODS: Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum. RESULTS: The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure. CONCLUSION: WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

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.

The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort.

BACKGROUND: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. METHODS AND FINDINGS: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. CONCLUSIONS: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

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.

Investigating the Barriers and Facilitators to Using Antiretroviral Therapy among Women Living with HIV in Plateau State, Nigeria.

BACKGROUND: Women and girls account for more than 50% of the global HIV population. In Nigeria, the proportion of women living with HIV on long-term antiretroviral therapy (ART) has been on the rise. Despite this, little research exists on their experiences regarding antiretroviral therapy use, especially for women living with HIV (WLHIV) in Plateau State, Nigeria. This study investigates the barriers and facilitators influencing antiretroviral therapy use among women living with HIV. METHODS: This study employed a qualitative research design, using focus groups, and included women (female sex workers, pregnant and non-pregnant women living with HIV) and the male partners of serodiscordant couples. Eligibility criteria were being 18 years of age or older, on antiretroviral therapy for more than one year/on pre-exposure prophylaxis (PrEP) for more than one month, and speaking English, Hausa, or both. Data coding utilized both inductive and deductive approaches, and standard content analysis was applied to develop emerging themes. RESULTS: Of the 106 participants, 88 were women living with HIV, and 18 were men in serodiscordant couples. The first facilitator shared by the participants was feeling healthier and stronger due to the antiretroviral therapy, which was also expressed by the male participants on PrEP as feeling good while taking the drug. Additional facilitators shared by the participants included weight gain and having a more positive outlook on life. Participants also disproportionately described barriers to using antiretroviral therapy, including experiences with emotional challenges, physical discomfort, and side effects of ART. Such barriers were linked to feelings of past regret, frustration, and disappointment. CONCLUSION: This study underscores the significance of maintaining a positive perspective on ART use, demonstrated by the connection between a positive outlook and weight gain, and highlights the hurdles that Plateau State's women living with HIV face in adhering to antiretroviral therapy. Policymakers and healthcare providers can utilize these findings to formulate targeted strategies aimed at minimizing identified barriers and enhancing antiretroviral therapy utilization among this population via peer- support groups, economic empowerment, and psychosocial support.

LAI-ART Awareness, Willingness, Barriers and Facilitators among Black Sexual Minority Men Living with HIV in the US South.

Black sexual minority men (BSMM) continue to bear a disproportionate burden of HIV in the United States, with the highest incidence and prevalence in the southern region of the country. In Texas, BSMM living with HIV (BSMM+) have the lowest rates of viral suppression of all SMM and have lower antiretroviral treatment (ART) adherence than white and Hispanic SMM. Long-acting injectable ART (LAI-ART) can potentially overcome several barriers to daily oral ART adherence (e.g., stigma, forgetfulness, pill fatigue). However, little is known about the knowledge, willingness, barriers, and facilitators regarding LAI-ART among BSMM+. From July 2022 to September 2023, we conducted in-depth, semi-structured interviews with 27 BSMM+ from the Houston and Dallas Metropolitan Areas, Texas. Data were analyzed using a thematic analysis approach. Most men knew about LAI-ART, but their understanding varied based on their existing sources of information. Some men were enthusiastic, some were cautious, and some reported no interest in LAI-ART. Barriers to LAI-ART included a lack of public insurance coverage of LAI-ART; fear of needles and side effects; the frequency of injection visits; the requirement of viral suppression before switching from oral ART to LAI-ART; and satisfaction with oral daily ART. Motivators of LAI-ART uptake included the eliminated burden of daily pills and reduced anxiety about possibly missing doses. BSMM+ may be among those who could most benefit from LAI-ART, though more research is needed to understand which factors influence their willingness and how the barriers to LAI-ART might be addressed, particularly among diverse communities of SMM of color.

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105.

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.

DeepARV: ensemble deep learning to predict drug-drug interaction of clinical relevance with antiretroviral therapy.

Drug-drug interaction (DDI) may result in clinical toxicity or treatment failure of antiretroviral therapy (ARV) or comedications. Despite the high number of possible drug combinations, only a limited number of clinical DDI studies are conducted. Computational prediction of DDIs could provide key evidence for the rational management of complex therapies. Our study aimed to assess the potential of deep learning approaches to predict DDIs of clinical relevance between ARVs and comedications. DDI severity grading between 30,142 drug pairs was extracted from the Liverpool HIV Drug Interaction database. Two feature construction techniques were employed: 1) drug similarity profiles by comparing Morgan fingerprints, and 2) embeddings from SMILES of each drug via ChemBERTa, a transformer-based model. We developed DeepARV-Sim and DeepARV-ChemBERTa to predict four categories of DDI: i) Red: drugs should not be co-administered, ii) Amber: interaction of potential clinical relevance manageable by monitoring/dose adjustment, iii) Yellow: interaction of weak relevance and iv) Green: no expected interaction. The imbalance in the distribution of DDI severity grades was addressed by undersampling and applying ensemble learning. DeepARV-Sim and DeepARV-ChemBERTa predicted clinically relevant DDI between ARVs and comedications with a weighted mean balanced accuracy of 0.729 ± 0.012 and 0.776 ± 0.011, respectively. DeepARV-Sim and DeepARV-ChemBERTa have the potential to leverage molecular structures associated with DDI risks and reduce DDI class imbalance, effectively increasing the predictive ability on clinically relevant DDIs. This approach could be developed for identifying high-risk pairing of drugs, enhancing the screening process, and targeting DDIs to study in clinical drug development.

Risk of transmission of HIV to infants during breast/chest feeding when mothers/birthing parents living with HIV are on antiretroviral therapy: a protocol for a rapid review.

INTRODUCTION: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature. METHODS AND ANALYSIS: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described. ETHICS AND DISSEMINATION: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences. PROSPERO REGISTRATION NUMBER: CRD42024499393.

Cost-Effectiveness and Budget Impact Analysis of the Implementation of Differentiated Service Delivery Models for HIV Treatment in Mozambique: a Modelling Study.

INTRODUCTION: In 2018, the Mozambique Ministry of Health launched guidelines for implementing differentiated service delivery models (DSDMs) to optimize HIV service delivery, improve retention in care, and ultimately reduce HIV-associated mortality. The models were fast-track, 3-month antiretrovirals dispensing, community antiretroviral therapy groups, adherence clubs, family approach and three one-stop shop models: adolescent-friendly health services, maternal and child health, and tuberculosis. We conducted a cost-effectiveness analysis and budget impact analysis to compare these models to conventional services. METHODS: We constructed a decision tree model based on the percentage of enrolment in each model and the probability of the outcome (12-month retention in treatment) for each year of the study period-three for the cost-effectiveness analysis (2019-2021) and three for the budget impact analysis (2022-2024). Costs for these analyses were primarily estimated per client-year from the health system perspective. A secondary cost-effectiveness analysis was conducted from the societal perspective. Budget impact analysis costs included antiretrovirals, laboratory tests and service provision interactions. Cost-effectiveness analysis additionally included start-up, training and clients' opportunity costs. Effectiveness was estimated using an uncontrolled interrupted time series analysis comparing the outcome before and after the implementation of the differentiated models. A one-way sensitivity analysis was conducted to identify drivers of uncertainty. RESULTS: After implementation of the DSDMs, there was a mean increase of 14.9 percentage points (95% CI: 12.2, 17.8) in 12-month retention, from 47.6% (95% CI, 44.9-50.2) to 62.5% (95% CI, 60.9-64.1). The mean cost difference comparing DSDMs and conventional care was US$ -6 million (173,391,277 vs. 179,461,668) and -32.5 million (394,705,618 vs. 433,232,289) from the health system and the societal perspective, respectively. Therefore, DSDMs dominated conventional care. Results were most sensitive to conventional care interaction costs in the one-way sensitivity analysis. For a population of 1.5 million, the base-case 3-year financial costs associated with the DSDMs was US$550 million, compared with US$564 million for conventional care. CONCLUSIONS: DSDMs were less expensive and more effective in retaining clients 12 months after antiretroviral therapy initiation and were estimated to save approximately US$14 million for the health system from 2022 to 2024.

Incidence of lost to follow up among HIV-positive children on antiretroviral therapy in Ethiopia: Systematic review and meta-analysis.

BACKGROUND: At the end of 2022, globally, only 46% of children (aged 0-14 years) on ART had suppressed viral loads. Viral load suppression is crucial to reduce HIV-related deaths. To suppress the viral load at the expected level, children must be retained in ART treatment. Nevertheless, lost to follow-up from ART treatment continues to be a global challenge, particularly, in developing countries. Previously, primary studies were conducted in Ethiopia to assess the incidence of lost to follow-up among HIV-positive children on ART treatment. However, variations have been seen among the studies. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence of lost to follow-up among HIV-positive children on ART and identify its associated factors in Ethiopia. METHODS: We searched PubMed, HINARI, Science Direct, Google Scholar, and African Journals Online to obtain articles published up to November 20, 2023. Critical appraisal was done using the Joanna Briggs Institute checklist. Heterogeneity was identified using I-square statistics. Funnel plot and Egger's tests were used to identify publication bias. Data was presented using forest plots and tables. Random and fixed-effect models were used to compute the pooled estimate. RESULTS: Twenty-four studies were included in the final analysis. The pooled incidence of lost to follow-up among HIV-positive children on ART was 2.79 (95% CI: 1.99, 3.91) per 100-child-year observations. Advanced HIV disease (HR: 2.20, 95% CI: 1.71, 2.73), having opportunistic infection (HR: 2.59, 95% CI: 1.39; 4.78), fair or poor ART treatment adherence (HR: 2.92, 95% CI: 1.31; 6.54) and children aged between 1-5 years (HR: 2.1,95% CI: 1.44; 2.95) were factors associated with lost to follow up among HIV positive children on ART. CONCLUSIONS: The overall pooled incidence of lost to follow-up among HIV-positive children on ART is low in Ethiopia. Therefore, counseling on ART drug adherence should be strengthened. Moreover, emphasis has to be given to children with advanced HIV stage and opportunistic infection to reduce the rate of lost to follow up among HIV-positive children on ART. TRIAL REGISTRATION: Registered in PROSPERO with ID: CRD42024501071.

Two-drug regimens for the treatment of HIV in Africa.

Two-drug regimens for the treatment of HIV are increasingly available. The oral regimen of dolutegravir plus lamivudine is recommended as a preferred option in multiple national guidelines but is not currently included in WHO HIV treatment guidelines nor widely used in Africa. Long-acting injectable cabotegravir and rilpivirine is being rolled out in the USA, Europe, and Australia but its use in sub-Saharan Africa is currently restricted to clinical trials. Given the increasing life expectancy, rising prevalence of non-communicable diseases, and resulting polypharmacy among people living with HIV, there are potential advantages to the use of two-drug regimens, particularly in African women, adolescents, and older adults. This Viewpoint reviews existing evidence and highlights the risks, benefits, and key knowledge gaps for the use of two-drug regimens in settings using the public health approach in Africa. We suggest that a two-drug regimen of dolutegravir and lamivudine can be safely used as a switch option for virologically suppressed individuals in settings using the public health approach once chronic hepatitis B has been excluded. Individuals with HIV who are switched to two-drug regimens should receive a full course of hepatitis B vaccinations. More efficacy data is needed to support dolutegravir plus lamivudine combination in the test and treat approach, and long-acting cabotegravir and rilpivirine in the public health system in sub-Saharan Africa.

Population-based nanopore sequencing of the HIV-1 pangenome to identify drug resistance mutations.

HIV-1 drug resistance genotypic tests have primarily been performed by Sanger sequencing of gene segments encoding different drug target proteins. Since the number of targets has increased with the addition of a new class of antiretroviral drugs, a simple high-throughput system for assessing nucleotide sequences throughout the HIV-1 genome is required. Here, we developed a new solution using nanopore sequencing of viral pangenomes amplified by PCR. Benchmark tests using HIV-1 molecular clones demonstrated an accuracy of up to 99.9%. In addition, validation tests of our protocol in 106 clinical samples demonstrated high concordance of drug resistance and tropism genotypes (92.5% and 98.1%, respectively) between the nanopore sequencing-based results and archived clinical determinations made based on Sanger sequencing data. These results suggest that our new approach will be a powerful solution for the comprehensive survey of HIV-1 drug resistance mutations in clinical settings.

Accuracy of Provider Predictions of Viral Suppression Among Adolescents and Young Adults With HIV in an HIV Clinical Program.

BACKGROUND: Providers caring for adolescents and young adults with HIV (AYA-HIV) mostly base their adherence counseling during clinical encounters on clinical judgment and expectations of patients' medication adherence. There is currently no data on provider predictions of viral suppression for AYA-HIV. We aimed to assess the accuracy of provider predictions of patients' viral suppression status compared to viral load results. METHODS: Providers caring for AYA-HIV were asked to predict the likelihood of viral suppression of patients before a clinical encounter and give reasons for their predictions. Provider predictions were compared to actual viral load measurements of patients. Patient data were abstracted from electronic health records. The final analysis included 9 providers, 28 patients, and 34 observations of paired provider predictions and viral load results. RESULTS: Provider prediction accuracy of viral suppression was low (59%, Cohen's Kappa = 0.16). Provider predictions of lack of viral suppression were based on nonadherence to medications, new patient status, or structural vulnerabilities (e.g., unstable housing). Anticipated viral suppression was based on medication adherence, history of viral suppression, and the presence of family or other social forms of support. CONCLUSIONS: Providers have difficulty accurately predicting viral suppression among AYA-HIV and may base their counseling on incorrect assumptions. Rapid point-of-care viral load testing may provide opportunities to improve counseling provided during the clinical encounter.

Accuracy of Provider Predictions of Viral Suppression among Adolescents and Young Adults with HIV in an HIV Clinical ProgramProviders caring for adolescents and young adults with HIV (AYA-HIV) mostly base their adherence counseling during clinical encounters on clinical judgment and expectations of patients' medication adherence. Currently, no data exist on provider predictions of viral suppression for AYA-HIV. We aimed to assess the accuracy of provider predictions of patients' viral suppression compared to viral load results. Providers caring for AYA-HIV were asked to predict the likelihood of viral suppression of patients before a clinical encounter with reasons for their predictions. Provider predictions were compared to actual viral load measurements of patients. Patient data were abstracted from electronic health records. The final analysis included nine providers, 28 patients, and 34 observations of paired provider predictions and viral load results. Provider prediction accuracy of viral suppression was low (59%, Cohen's Kappa=0.16). Provider predictions of lack of viral suppression were based on non-adherence to medications, new patient status, or structural vulnerabilities (e.g., unstable housing). Anticipated viral suppression was based on medication adherence, history of viral suppression, and presence of family or other social forms of support. Providers have difficulty predicting viral suppression among AYA-HIV and may base counseling on incorrect assumptions. Rapid point-of-care viral load testing may provide opportunities to improve counseling.

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.