Determinants of antiretroviral therapy adherence among transgender women in South Africa.

BACKGROUND:  Transgender women bear a huge burden of human immunodeficiency virus (HIV) in South Africa. However, they are not fully engaged in healthcare across the HIV continuum of care. In addition, transgender women face multiple facets of stigma and discrimination as well as socio-economic inequalities, which all have a negative impact on antiretroviral therapy (ART) adherence. OBJECTIVE:  The study aimed at exploring and describing the experiences of ART adherence of transgender women living with HIV in the Buffalo City Metro Municipality. METHODS:  The study employed an interpretative phenomenological analysis (IPA) design. Twelve participants were enrolled using a snowballing sampling technique. Data were collected using semi-structured interviews and analysed using an IPA framework. RESULTS:  While exploring determinants to ART adherence among transgender women living with HIV in Buffalo City Metro, two superordinate themes emerged: enablers to ART adherence and psychosocial factors promoting adherence. The study found that factors such as differentiated ART service delivery, ARV medicines-related factors, motivators for taking treatment and support systems facilitated ART adherence. CONCLUSION:  Emerging from this study is the need to scale up differentiated, person-centred ART service deliveries that will enhance access and adherence to treatment for transgender women.Contribution: This study provides unique insights on factors enhancing ART adherence among transgender women. There is a paucity of literature on access to HIV care services for key and vulnerable populations, and these findings will be shared in the country and in the region.

Experiences of patients living with HIV and AIDS on antiretroviral therapy in Accra, Ghana.

BACKGROUND:  The human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS) pandemic has greatly affected Africa, particularly Ghana. The pandemic remains a public health concern, particularly in terms of accessing essential medication and improving quality of life for people living with the disease. OBJECTIVES:  This study aimed to explore and describe the experiences of persons diagnosed and living with HIV who are on antiretroviral therapy. METHOD:  A qualitative, exploratory, descriptive, and contextual design was used. The research population included persons diagnosed with HIV who were receiving antiretroviral therapy at three public hospitals in Ghana. Data saturation was achieved after conducting 15 semi-structured interviews. Creswell's six steps of data analysis were used to analyse the data, which resulted in the emergence of one main theme and six sub-themes. RESULTS:  The main theme identified by the researchers highlighted the participants' diverse experiences of being diagnosed and living with HIV. It was found that the study participants expressed shock, disbelief, surprise, and fear of death after being diagnosed with HIV. The participants also experienced stigmatisation, discrimination, and rejection. CONCLUSION:  There is a need for further research on the extent of discrimination and stigmatisation and the effect on optimal adherence to antiretroviral therapy. Continuous public education on HIV is required to limit the extent of discrimination and stigmatisation.Contribution: The study has highlighted the various emotions related to stigma and discrimination expressed by persons living with HIV (PLHIV). The findings will guide policy on eliminating discrimination and stigmatisation for people living with HIV.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

Characteristics of drug resistance mutations in ART-experienced HIV-1 patients with low-level viremia in Zhengzhou City, China.

Although most people living with HIV (PLWH) receiving antiretroviral therapy (ART) achieve continuous viral suppression, some show detectable HIV RNA as low-level viremia (LLV) (50-999 copies/mL). Drug resistance mutations (DRMs) in PLWH with LLV is of particular concern as which may lead to treatment failure. In this study, we investigated the prevalence of LLV and LLV-associated DRMs in PLWH in Zhengzhou City, China. Of 3616 ART-experienced PLWH in a long-term follow-up cohort from Jan 2022 to Aug 2023, 120 were identified as having LLV. Of these PLWH with LLV, we obtained partial pol and integrase sequences from 104 (70 from HIV-1 RNA and 34 from proviral DNA) individuals. DRMs were identified in 44 individuals. Subtyping analysis indicated that the top three subtypes were B (48.08%, 50/104), CRF07_BC (31.73%, 33/104), and CRF01_AE (15.38%, 16/104). The proportions of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) associated DRMs were 23.83% (24/104), 35.58% (37/104), 5.77% (6/104), and 3.85% (4/104), respectively, which contributed to an overall prevalence of 42.31% (44/104). When analyzed by individual DRMs, the most common mutation(s) were V184 (18.27%, 19/104), followed by V179 (11.54%, 12/104), K103 (9.62%, 10/104), Y181 (9.62%, 10/104), M41 (7.69%, 8/104), and K65R (7.69%, 8/104). The prevalence of DRMs in ART-experienced PLWH with LLV is high in Zhengzhou City and continuous surveillance can facilitate early intervention and provision of effective treatment.

Assessing the resilience of HIV healthcare services provided to adolescents and young adults after the COVID-19 pandemic in the city of Beira (Mozambique): an interrupted time series analysis.

BACKGROUND: The COVID-19 pandemic has put the provision of health services globally at risk. In Sub-Saharan Africa, it had a major impact on HIV services. However, there is a lack of data on the post-pandemic period. This study aims to evaluate the resumption of HIV services and retention in care for adolescents and young people in the period following the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted using interrupted time series analysis. Three periods were considered: pre-pandemic (form June 2019 to March 2020), pandemic (form April 2020 to March 2022) post-pandemic (from April 2022 to March 2023). Six outcome measures were considered: number of outpatient visits, HIV tests, HIV positivity ratio, the antiretroviral treatment (ART) non-adherence ratio, recall ratio, and the return ratio for adolescent and young adults on ART. RESULTS: During the study period, 447,515 outpatient visits and 126,096 HIV tests were recorded. After a reduction at the beginning of the pandemic period, both visits and tests increased during the pandemic (p < 0.05) and decreased in the post-pandemic (p < 0.05), recovering the pre-pandemic trends. The HIV positivity ratio slightly decreased from 3.3% to 1.7% during the study period (p < 0.05). The ART non-adherence ratio decreased from 23.4% to 2.4% throughout the study period (p < 0.05), with a drop at the beginning of the post-pandemic period (p < 0.05). The recall ratio increased during the study period (p < 0.05) with a drop at the beginning of the pandemic and post-pandemic periods (p < 0.05). The return ratio decreased at the beginning of the pandemic (p < 0.05) but returned to the pre-pandemic ratio in the post-pandemic period. CONCLUSIONS: The post-pandemic values of the investigated outcomes were comparable to pre-pandemic period, or even improved. Differently from other services, such as the community activities, that have been severely affected by COVID-19 pandemic, the HIV service system has shown resilience following emergency situation.

"I am adhering to HIV treatment so that I can live to support her": A qualitative study of upward intergenerational support in South Africa.

Background: Intergenerational family care, which was upended by the HIV epidemic in sub-Saharan Africa (SSA), may return to a pre-HIV era arrangement as access to antiretroviral therapy (ART) expands and treated adults can once again provide support for older household members. Empirical research has demonstrated positive 'spillover effects' of ART uptake from treated adults to younger generations, yet much less is known about the nature and breadth of such effects to older generations. This study explores the role and lived experiences among adults who take up ART and those of an older generation with whom they live. Methods: We conducted a qualitative study consisting of semi-structured interviews (n = 46) embedded in the Agincourt Health and Demographic Surveillance System (HDSS) in rural South Africa, between July and September 2022. We purposefully sampled two respondent categories: (i) young or middle-aged adults on ART (aged 18-59 years old); and (ii) older adults (aged ≥60 years old) who were affiliated with a young or middle-aged adult on ART. We used thematic content analysis to extract, code, and categorise relevant text by types of upward spillover effects from ART in younger adults to older adults. Quantitative data was extracted from the existing Agincourt HDSS database and matched to qualitative interview data based on Clinic link unique identifiers of study participants. Results: Mean age was 41 years among young or middle-aged adults (n = 29) and 72 years among older adults (n = 17). Among younger adults, time on ART ranged from five months to more than 21 years. Both young or middle-aged adults on ART and older adults reported positive spillover effects for older adults across five main tiers: caregiving, financial support, physical and mental health, living arrangements and household relationships, and stigma and reputation. Spillover challenges included financial costs and caregiving responsibilities following ART initiation of young or middle-aged adults, although these additional caregiving responsibilities were generally not perceived as particularly burdensome. Conclusions: ART is likely to benefit older adults in South Africa whose families are affected by HIV. This study identified a wide range of perceived spillover effects from ART in younger adults to older adults, including improvements to upward intergenerational support. These qualitative findings offer a guide to researchers, policymakers, and donors to capitalise on the broader societal effects of a large-scale health intervention to further support family structures and meet the needs of a growing older population.

Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.

HIV-infected (HIV+) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV+ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1ß, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV+ individuals than healthy controls. Increasing CD4 T cell counts in the HIV+ cohort did not significantly change the circulating cytokine levels, although levels of IL-1ß increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV+ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV+ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1ß and IL-17 were slightly elevated. Furthermore, increasing age of the HIV+ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV+ individuals had higher levels of TNF-α, IFN-γ, and IL-1ß. In summary, our findings show that HIV+ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.

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.

Projected Life Expectancy for Adolescents With HIV in the US.

Importance: Life expectancy is a key measure of overall population health. Life expectancy estimates for youth with HIV in the US are needed in the current HIV care and treatment context to guide health policies and resource allocation. Objective: To compare life expectancy between 18-year-old youth with perinatally acquired HIV (PHIV), youth with nonperinatally acquired HIV (NPHIV), and youth without HIV. Design, Setting, and Participants: Using a US-focused adolescent-specific Monte Carlo state-transition HIV model, we simulated individuals from age 18 years until death. We estimated probabilities of HIV treatment and care engagement, HIV progression, clinical events, and mortality from observational cohorts and clinical trials for model input parameters. The simulated individuals were 18-year-old race and ethnicity-matched youth with PHIV, youth with NPHIV, and youth without HIV; 47%, 85%, and 50% were assigned male sex at birth, respectively. Individuals were categorized by US Centers for Disease Control and Prevention-defined HIV acquisition risk: men who have sex with men, people who ever injected drugs, heterosexually active individuals at increased risk for HIV infection, or average risk for HIV infection. Distributions were 3%, 2%, 12%, and 83% for youth with PHIV and youth without HIV, and 80%, 6%, 14%, and 0% for youth with NPHIV, respectively. Among the simulated youth in this analysis, individuals were 61% Black, 24% Hispanic, and 15% White, respectively. Exposures: HIV status by timing of acquisition. Main Outcomes: Life expectancy loss for youth with PHIV and youth with NPHIV: difference between mean projected life expectancy under current and ideal HIV care scenarios compared with youth without HIV. Uncertainty intervals reflect varying adolescent HIV-related mortality inputs (95% CIs). Results: Compared with youth without HIV (life expectancy: male, 76.3 years; female, 81.7 years), male youth with PHIV and youth with NPHIV had projected life expectancy losses of 10.4 years (95% CI, 5.5-18.1) and 15.0 years (95% CI, 9.3-26.8); female youth with PHIV and youth with NPHIV had projected life expectancy losses of 11.8 years (95% CI, 6.4-20.2) and 19.5 years (95% CI, 13.8-31.6), respectively. When receiving ideal HIV care, life expectancy losses were projected to improve for youth with PHIV (male: 0.5 years [95% CI, 0.3-1.8]: female: 0.6 years [95% CI, 0.4-2.1]) but were projected to persist for youth with NPHIV (male: 6.0 years [95% CI, 5.0-9.1]; female: 10.4 years [95% CI, 9.4-13.6]). Conclusions: This adolescent-focused microsimulation modeling analysis projected that youth with HIV would have shorter life expectancy than youth without HIV. Projected differences were larger for youth with NPHIV compared with youth with PHIV. Differences in mortality by sex at birth, sexual behavior, and injection drug use contributed to lower projected life expectancy among youth with NPHIV. Interventions focused on HIV care and social factors are needed to improve life expectancy for youth with HIV in the US.

A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico.

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in Tigray Region, Ethiopia: a case-control study.

BACKGROUND: Multidrug-resistant tuberculosis is a type of tuberculosis that is resistant to at least the first-line antituberculosis drugs namely, rifampicin and isoniazid. However, most of these studies were limited only to a single hospital. Therefore, this study aimed to identify the determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in the Tigray region of Ethiopia. METHODS: Hospital-based unmatched case-control study was conducted from 1 April 2019 to 30 June 2019. A simple random sampling method was used to select the required sample size. Variables at a p value less than 0.25 in bivariate analysis were entered into a multivariable analysis to identify the determinant factors of multidrug-resistant tuberculosis. Finally, the level of significance was declared at p<0.05. RESULTS: Rural residence (adjusted OR (AOR) 2.54; 95% CI 1.34 to 4.83), HIV (AOR 4.5; 95% CI 1.4 to 14.2), relapse (AOR 3.86; 95% CI 1.98 to 7.5), return after lost follow-up (AOR 6.29; 95% CI 1.64 to 24.2), treatment failure (AOR 5.87; 95% CI 1.39 to 24.8) were among the determinants of multidrug-resistant tuberculosis. CONCLUSION: Rural residence, HIV, relapses, return after lost follow-up and treatment failure were the identified determinant factors of multidrug-resistance tuberculosis.

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.

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.

Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children.

Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.

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.

Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

Screening for Hypertension in adolescents living with HIV: Protocol for a cluster randomized trial to improve guideline adherence.

BACKGROUND: Although AIDS-related deaths have reduced with increased access to antiretroviral care, cardiovascular disease-related morbidities among persons living with HIV are rising. Contributing to this is the higher incidence of Hypertension among Persons Living with HIV. The duration of exposure to the virus and antiretroviral drugs plays a vital role in the pathogenesis, putting perinatally infected children and adolescents at higher risk than behaviorally-infected ones, supporting the calls for increased surveillance of Hypertension among them. Despite the availability of guidelines to support this surveillance, the blood pressure (BP) of adolescents living with HIV (ADLHIV) is not checked during clinical visits. This study aims to assess the effect of a theory-based intervention on healthcare workers' adherence to the guidelines for hypertension screening among adolescents. METHODS: A multi-facility cluster-randomized study will be conducted. The clusters will be 20 antiretroviral therapy sites in the Greater Accra Region of Ghana with the highest adolescent caseload. Data will be extracted from the folders of adolescents (10-17 years) who received care in these facilities six months before the study. The ART staff of intervention facilities will receive a multicomponent theory of planned behaviour-based intervention. This will include orientation on hypertension risk among ADLHIV, provision of job aids and pediatric sphygmomanometers. Six months after the intervention, the outcome measure will be the change from baseline in the proportion of ADLHIV whose BP was checked during clinical visits. The calculated sample size is 400 folders. IMPLICATIONS OF FINDINGS: This study will generate evidence on the effectiveness of a multicomponent theory-based intervention for improving the implementation of clinical practice guidelines. TRIAL REGISTRATION: PACTR202205641023383.