We assessed the association between dolutegravir (DTG)-based antiretroviral therapy and kidney abnormalities among young people living with HIV in Kampala, Uganda. Cross-sectional albumin–creatinine ratio (ACR), proteinuria, and estimated glomerular filtration rate (eGFR) were measured. Among 483 participants, the mean serum creatinine was higher (0.68 vs. 0.59) and creatinine-based eGFR lower (118.8 vs. 113.9), among those on TDF/DTG. Cystatin C–based eGFR, prevalences of elevated ACR (9.6

Federally qualified health centers (FQHCs) in the United States began the widespread use of telemedicine for HIV care during the COVID-19 pandemic. During a mature phase of the pandemic, we sought to increase the uptake of telemedicine, characterize uptake by modality (telephone versus video), and explore the association of telemedicine use with viral suppression. We implemented a multi-pronged intervention to increase telemedicine (particularly with video) and performed a prospective cohort study to evaluate this intervention. The intervention included: (1) provision of an easy-to-use video visit platform; (2) training on telemedicine best practices; (3) computer-based and support staff reminders to offer a choice of telephone or video telemedicine; (4) a telemedicine navigator; and (5) quarterly quality improvement meetings. We conducted baseline and endline surveys and chart reviews with a cohort of people living with HIV (PLHIV) to measure telemedicine use (including offer, uptake, and visit completion by modality) and changes in viral load. We used mixed effects regression models to evaluate the intervention’s association with viral suppression over time (< 40 copies/mL). We enrolled 271 PLHIV between March and November 2022 and implemented the intervention from August 2022-October 2023. Telemedicine visits (telephone and video) in this cohort increased during the intervention period from 13

We assessed the association between dolutegravir (DTG)-based antiretroviral therapy and kidney abnormalities among young people living with HIV aged 10-24 years in Kampala, Uganda. In this cross-sectional study, albumin-creatinine ratio (ACR), proteinuria, and estimated glomerular filtration rate (eGFR) were measured. Among 483 participants, 78% received tenofovir (TDF)/DTG. Mean serum creatinine was higher and creatinine-based eGFR lower among those on TDF/DTG, while cystatin C and cystatin C-based eGFR were similar. The prevalence of elevated ACR, proteinuria, and eGFR <90 ml/min/1.73m2 was similar. Kidney abnormalities were common, supporting the need for longitudinal studies to clarify chronic kidney disease risk.

INTRODUCTION:We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS:Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS:Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS:Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Background:We evaluated baseline hypertension prevalence and control and risk of major adverse cardiovascular events (MACEs) among people with HIV in REPRIEVE who had low to moderate traditional cardiovascular disease (CVD) risk. Methods:Hypertension at baseline was defined by (1) a preexisting diagnosis regardless of antihypertensive treatment or (2) systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg without a prior diagnosis. We estimated the prevalence of the composite hypertension and control outcomes and calculated adjusted prevalence ratios controlling for traditional CVD risk factors using log binomial regression. We explored the relationship between hypertension and MACE using cause-specific Cox proportional hazards models. Results:Of 7769 participants enrolled from 5 regions, the median age was 50 years, and 2419 (31%) were women. The prevalence of baseline hypertension was 36% (n = 2780) with geographic variation. Among these, 1911 (69%) individuals had a preexisting hypertension diagnosis; the remainder (n = 869, 31%) were undiagnosed. Region and traditional CVD risk factors were associated with hypertension prevalence, with obese and overweight body mass index having the highest adjusted prevalence ratios (1.80 [95% CI, 1.67-1.95] and 1.38 [95% CI, 1.28-1.49], respectively). Among those with preexisting hypertension, 40% were uncontrolled, with regional variation. Hypertension at baseline was associated with an increased hazard of MACE (hazard ratio, 2.00; 95% CI, 1.57-2.55) and key components of MACE, including myocardial infarction and stroke. Conclusions:Approximately 1 in 3 REPRIEVE participants had hypertension at baseline. Hypertension was frequently suboptimally controlled. These findings highlight the need for improved screening and optimized treatment of hypertension in people with HIV.

OBJECTIVE:We evaluated preferences for differentiated service delivery of oral preexposure prophylaxis (PrEP) versus clinic pick-up among oral PrEP-experienced pregnant and breastfeeding women (PBFW) in South Africa and Kenya. DESIGN AND METHODS:From September 2021 to February 2022, we surveyed PBFW in oral PrEP studies in South Africa and Kenya. We asked participants about their PrEP delivery preferences and used logistic regression models adjusted for age and country to identify predictors of preferring community over clinic-based PrEP delivery. RESULTS:We surveyed 394 South African and Kenyan PBFW (73% postpartum, median age 28 years). Overall, 59.5% of South African participants ( n  = 113) and 24.5% of Kenyan participants ( n  = 50, P  < 0.01) were interested in community PrEP delivery, most frequently due to convenience ( n  = 80, 49.1%) and lower transportation costs ( n  = 78, 47.9%). Participants preferred clinic PrEP pick-up due to privacy ( n  = 174, 75.3%) and desire to see a healthcare provider ( n  = 83, 35.9%). Preference for community PrEP delivery was positively associated with South African participants [adjusted odds ratio (aOR) = 4.32, 95% confidence interval (CI) = 2.80-6.67], PrEP stigma (aOR = 2.59, 95% CI = 1.58-4.23), completing secondary school or higher (aOR = 1.84, 95% CI = 1.17-2.92), and transportation cost to clinic (aOR = 1.39, 95% CI = 1.10-1.75). Preference of community PrEP delivery was negatively associated with age (aOR = 0.68 per 10-year increase, 95% CI = 0.49-0.95) and having one or more sexual partners versus no sexual partners (aOR = 0.34, 95% CI = 0.12-0.95). CONCLUSIONS:Oral PrEP-experienced PBFW in South Africa and Kenya described varied preferences for community PrEP delivery. Associations with community-based PrEP delivery preference identified in this analysis may be useful in the development of context-specific DSD interventions targeting PBFW.

BACKGROUND:People living with HIV have an increased risk of cardiovascular disease, but data on the development and consequences of hypertension remain limited. Using data from REPRIEVE, a global randomised trial of pitavastatin for primary cardiovascular prevention among people with HIV, we evaluated whether pitavastatin reduces the incidence of hypertension among participants without hypertension at baseline and whether incident hypertension is associated with subsequent major adverse cardiovascular events (MACE). METHODS:We conducted a prespecified secondary analysis of participants without evidence of hypertension at REPRIEVE entry (baseline). REPRIEVE (NCT02344290) was a global, randomised, double-blind, placebo-controlled trial that enrolled adults with HIV aged 40-75 years at low-to-moderate atherosclerotic cardiovascular risk, receiving stable antiretroviral therapy. The primary outcome in this secondary analysis was incident hypertension based on clinical diagnosis according to standard criteria. Included participants were those without hypertension at baseline; excluded were those with documented hypertension, antihypertensive treatment use, systolic blood pressure of 140 mm Hg or higher, or diastolic blood pressure of 90 mm Hg or higher. The association between incident hypertension and a secondary outcome of MACE was evaluated in a time-updated analysis. Analyses used both Cox and Fine-Gray proportional hazards models and Poisson regression. FINDINGS:Of 7769 participants enrolled in REPRIEVE, 4989 (64%) without hypertension at baseline were included (2496 assigned to pitavastatin and 2493 to placebo) in this secondary analysis. The median age was 49 years (IQR 45-54); 1464 (29%) were women and 3525 (71%) men; and the median systolic and diastolic blood pressures at baseline were 102 mm Hg and 76 mm Hg, respectively. Over a median follow-up of 5·0 years (IQR 4·4-5·8), 668 (13%) participants developed hypertension. Participants randomly assigned to pitavastatin showed a modestly lower incidence of hypertension (24·7 per 1000 person-years vs 29·6 per 1000 person-years), corresponding to a 17% relative risk reduction (cause-specific hazard ratio [HR] 0·83, 95% CI 0·71-0·97; p=0·017). Risk factors of incident hypertension included old age, high BMI, metabolic syndrome, reduced estimated glomerular filtration rate (eGFR), and Black race in high-income regions. Among participants with incident hypertension, 581 (87%) initiated antihypertensive therapy. Of 213 who initiated antihypertensive therapy after diagnosis of hypertension, 159 (74·6%) were controlled 4 years after diagnosis. Incident hypertension was associated with a higher risk of MACE during follow-up (subdistribution HR 2·16, 95% CI 1·32-3·52) in modelling adjusted for baseline cardiovascular risk score. INTERPRETATION:These findings suggest additional cardiovascular benefits of pitavastatin on hypertension among people with HIV targeted for primary cardiovascular prevention. FUNDING:National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, ViiV Healthcare, Instituto de Salud Carlos III, and the European Regional Development Fund.

BACKGROUND:Long-acting antiretroviral therapy (LA-ART) may reduce adherence barriers for postpartum women with HIV (PPWH), reducing vertical transmission (VT) and improving pediatric life expectancy (pLE), but efficacy and drug costs are uncertain. METHODS:Using a microsimulation model, we simulated mother-infant dyads for two cohorts of PPWH engaged in care, receiving oral tenofovir/lamivudine/dolutegravir (TLD) in pregnancy, and facing adherence challenges in Zimbabwe: mothers without (NVS) and with (VS) viral suppression at delivery. We modeled two post-delivery strategies: standard of care (SOC: TLD continuation) or LA-ART (switching to LA-cabotegravir/rilpivirine [CAB/RPV]). Key inputs included: 6-month-postpartum viral suppression (LA-ART: NVS = 85%/VS = 90%; SOC: NVS = 63%/VS = 78%), ART costs/year (CAB/RPV=$144/TLD=$43.20), and VT risk (0.06%-0.89%/month, range by maternal RNA). Outcomes include VT, pLE, costs (maternal ART in breastfeeding plus pediatric HIV-related lifetime care), and incremental cost-effectiveness ratios (ICERs, $/year-of-life-saved [YLS]; cost-effective: ICER≤$800/YLS [0.5× Zimbabwe GDP]. RESULTS:LA-ART would reduce VT compared with SOC (NVS: from 7.49% to 6.58%/VS: from 4.17% to 3.80%), averting ∼160 infections/year in Zimbabwe. For NVS, LA-ART would improve pLE (SOC = 66.08y, LA-ART = 66.40y) at nearly equal cost (SOC = $764/child, LA-ART = $763/child); LA-ART would not be cost-effective if CAB/RPV cost >$228/year or 6-month suppression were <74%. For VS, LA-ART would lead to higher pLE and costs (67.52y, $555/child) than SOC (67.40y, $445/child), with ICER=$2449/YLS; LA-ART would become cost-effective if CAB/RPV cost ≤$84/year. CONCLUSIONS:LA-ART for breastfeeding women experiencing adherence challenges could reduce infant infections. If efficacies and costs are confirmed, LA-ART for NVS women would improve outcomes and be minimally cost-saving; for VS women, LA-ART would be cost-effective in Zimbabwe at costs ≤$84/year.

OBJECTIVES:Severe tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature of severe HIV/TB in sub-Saharan Africa. DESIGN AND SETTING:We analyzed proteomic data from two prospective observational cohorts of adults hospitalized with severe undifferentiated infection in Uganda: an urban discovery cohort (Entebbe, n = 241) and a rural validation cohort (Tororo, n = 253). PATIENTS:Adults (age ≥ 18 yr) hospitalized with severe febrile illness. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Across both cohorts, severe HIV/TB was common, affecting 18% of participants in the discovery cohort and 21% in the validation cohort. Overall mortality was significant (30-d mortality of 22% in the discovery cohort and 60-d mortality of 26% in the validation cohort). Participants were stratified into three HIV/TB phenotypes: HIV-negative without TB, PLWH without TB, and PLWH with microbiologically diagnosed TB. We applied ordinal random forest models in the discovery cohort as a supervised feature-selection approach to identify proteins associated with progressive HIV/TB phenotype. In both cohorts, PLWH with microbiologically diagnosed TB were at highest risk of critical illness and death (30-d mortality of 42% in the discovery cohort and 60-d mortality of 52% in the validation cohort). An eight-protein signature reliably distinguished this phenotype, reflecting mediators of macrophage/dendritic cell activation (lysosome-associated membrane glycoprotein 3), natural killer cell and T-cell stimulation and cytotoxicity (cluster of differentiation 70, class I-restricted T-cell-associated molecule), B-cell activation (immunoglobulin lambda constant 2), protease-mediated tissue injury (protease, serine 2 [trypsin-2]), dysregulated coagulation (serpin peptidase inhibitor, clade A [alpha-1 antitrypsin], member 5), extracellular matrix remodeling (epidermal growth factor-containing fibulin-like extracellular matrix protein 1), and growth hormone/insulin-like growth factor axis dysregulation (insulin-like growth factor binding protein 3). CONCLUSIONS:We identified an immunologic signature of severe HIV/TB defined by mediators of macrophage/dendritic cell and cytotoxic lymphocyte activation, extracellular matrix remodeling, and dysregulated coagulation. These findings offer new insight into HIV/TB pathobiology and highlight potential targets for host-directed therapies in this high-risk population.

After the transition to pediatric dolutegravir-based regimens, viral load (VL) suppression among children with HIV (CWH) in Malawi has remained suboptimal. This mixed-methods study assessed factors associated with high VL among young CWH on dolutegravir-based antiretroviral therapy (ART) and explored adherence barriers from primary-caregiver and healthcare worker perspectives. Between April-July 2023, we performed an unmatched case-control study at 49 Malawian health facilities. We included CWH aged ≤9 years, on dolutegravir-based ART, with a routine VL test-result that was high (≥1,000 copies/mL) for cases, or suppressed (<200 copies/mL) for controls. Using mixed-effect modified Poisson regression, we determined factors associated with high VL, adjusting for sex, site and district. To assess adherence barriers, we conducted in-depth interviews (IDIs) with randomly selected caregivers of CWH with high VL and with healthcare workers providing pediatric HIV care. Data were analyzed using a hybrid thematic approach that combined deductive and inductive coding strategies. We enrolled 538 CWH: 222 cases, with high VL and 316 controls, with suppressed VL. Duration on ART > 4 years (aRR = 0.86, 95% CI: 0.77-0.95) and ≥2 interruption in treatment episodes (≥28 days late for clinic appointment) in the 12 months before VL sample collection (aRR = 1.47, 95% CI: 1.28-1.68) were significantly associated with high VL. Through 54 IDIs (30-caregivers, 24-healthcare workers), five key adherence challenges were identified and affected the children ≤5 years the most: resistance to daily medication, difficulties taking multiple pills, food insecurity, fear of unintentional disclosure, and inability to attend clinic appointments consistently. This study highlights that behavioral, socio-economic and psychosocial factors influences ART adherence among CWH. Duration on ART and recent interruptions in treatment were associated with high VL, stressing the need for targeted interventions that will require health-system and client-level approaches to improve VL suppression among CWH in Malawi and similar settings.

OBJECTIVES:In Los Angeles, cisgender men who have sex with men (MSM) - particularly Black/African American and Latinx individuals - are a high-priority population for new HIV prevention interventions. Incentive programs that pay people for engaging in healthy behaviors, also known as "conditional cash transfers" (CCTs), are a promising strategy, but there is little evidence about their use in Black/African American and Latinx cisgender MSM. DESIGN AND METHODS:We surveyed 133 cisgender MSM who identified as Black/African American or Latinx and included a discrete choice experiment to elicit their preferences for CCTs to incentivize preexposure prophylaxis (PrEP) use and, separately, HIV testing. RESULTS:Our findings suggest that respondents preferred more frequent payments of higher monetary value (e.g., a 35.2 percentage point increased probability of choosing a PrEP use CCT with $1200 versus $300 payment, and a 49.7 percentage point increased probability of choosing an HIV testing CCT with $1200 versus $300 payment). Additionally, respondents showed a preference for receiving CCT payments in cash over gift card payments (a 9.4 percentage point increased preference in the PrEP use CCT, and an 11 percentage point increased preference in the HIV testing CCT), particularly among those who were unemployed. Younger respondents had a stronger preference for more frequent payments. Higher monetary amounts were more strongly preferred by those with greater educational attainment and those who were employed. CONCLUSIONS:This preimplementation research highlights important, and heterogeneous, preferences in the design details of a HIV prevention CCT for Black/African American and Latinx cisgender MSM in Los Angeles.

INTRODUCTION:Providing pregnant and lactating people (PLP) with choice in HIV pre-exposure prophylaxis (PrEP) methods, including long-acting injectable cabotegravir (CAB-LA), may mitigate barriers to effective PrEP use. We evaluated PrEP preferences and acceptability among PLP offered CAB-LA versus oral PrEP in South Africa. METHODS:The PrEPared to Choose study in Cape Town, South Africa, enrolled young people ages 15-29 at one public clinic and one community-based mobile clinic. Using informed choice counselling, participants were offered oral PrEP or CAB-LA, with the option to switch methods at follow-up visits over 18 months. We report baseline CAB-LA and oral PrEP initiations among PLP in the study, acceptability of their initial choice within 3 months of enrolment and theoretical preferences regarding PrEP methods that may become available to PLP. We report descriptive statistics and use Chi-square and Fisher's exact to compare responses by initiated PrEP method and pregnancy status. RESULTS:From February to August 2024, we enrolled 58 PLP (n = 30 pregnant, n = 28 breastfeeding). Median age 23 years (IQR 19.5-26). Of 30 pregnant participants, 23 (77%) initiated CAB-LA and seven (23%) oral PrEP; among 28 breastfeeding participants, 25 (89%) initiated CAB-LA and three (11%) oral PrEP. Of enrolled PLP, 36 (62%, n = 13 pregnant, n = 23 breastfeeding) completed the acceptability survey. Of these, 83% (n = 12/13 pregnant, n = 20/23 breastfeeding) chose and received CAB-LA, and the remaining (n = 4) chose and received oral PrEP. PLP who received CAB-LA reported liking its ease of use (69%; n = 22/32) and long-acting protection (44%; n = 14/32). Half of CAB-LA users disliked side effects (e.g. injection site pain), although 41% of PLP (n = 13/32) described no CAB-LA dislikes. Almost all (97%; n = 31/32) PLP currently using CAB-LA were interested in continuing CAB-LA, and all PLP using oral PrEP reported interest in trying CAB-LA in the future. Eighty-six percent of surveyed PLP (n = 31/36) did not want to try the dapivirine vaginal ring. CONCLUSIONS:PLP in South Africa had a strong preference for CAB-LA over oral PrEP, and CAB-LA was found to be highly acceptable. Further research is needed to evaluate the effect of offering choice of PrEP methods, including CAB-LA, on PrEP continuation among PLP.

BACKGROUND:The information environment may be an important determinant of vaccination and other health behaviors including in low-income countries. METHODS:We administered a survey to 895 Malawian adults, asking about people's COVID-19 vaccination history and their exposure to information (information sources and tone of this information) and misinformation (exposure to and belief in conspiracy theories) about the COVID-19 vaccine. RESULTS:Just under half (43%) of respondents had received at least one dose of the COVID-19 vaccine. Respondents heard about the COVID-19 vaccine from a median of 7 sources, most commonly from friends and neighbors, health care workers, and radio (each reported by >90%). Social media are the least positively- or neutrally-framed sources of information; and traditional medicine practitioners are the most common negatively-framed source of information. There is less information access among women, rural residents, and people with lower educational attainment. Many people hear conspiracy theories but say that they do not believe them. Hearing more COVID-19 vaccine information is positively associated with COVID-19 vaccination (aOR 1.09, 95% CI [1.03-1.15]), while believing COVID-19 vaccine misinformation is negatively associated (aOR 0.78, 95% CI [0.68-0.89]). CONCLUSIONS:Vaccination programs should communicate through multiple information sources and find ways to reach groups with less information exposure.

BACKGROUND:Malawi has a significant burden of hypertension, including for people with HIV. The World Health Organization recommends integrated HIV-hypertension care, but such integration is not widely implemented in resource-constrained settings. OBJECTIVE:This study explored barriers to hypertension care in Malawi from the perspectives of healthcare providers and health system leaders. METHODS:We conducted a qualitative study of providers and health system leaders across 14 health facilities in Malawi. Interviews explored hypertension services in integrated (HIV and hypertension) and non-integrated clinics to identify barriers to hypertension care and compare barriers by integration status. Interview guides and analysis used the Consolidated Framework for Implementation Research. All transcripts were double coded and thematic analysis was performed. RESULTS:From April-May 2023, we interviewed 33 individuals (25 providers and 8 health system leaders). Barriers to hypertension care were largely the same in integrated and non-integrated clinics and included stockouts of antihypertensive medications, lack of equipment, lack of provider training, and weak medical record systems. Providers working in integrated care emphasized the benefits of reduced burden for clients and improved quality of care but also reported unique challenges, including capacity constraints (due to the large number of clients) and inability to provide aligned dispensing of antihypertensive medications and ART (due to antihypertensive medication stockouts). CONCLUSIONS:Barriers to integrated HIV and hypertension care in our study largely reflected challenges for hypertension care more broadly. Future efforts should focus on provider training, supply chain strengthening, equipment procurement, and medical record system strengthening to improve outcomes for people with hypertension and hypertension-HIV multimorbidity.

Uptake of the human papillomavirus (HPV) vaccine is suboptimal globally. Effective interventions are needed to meet the global goal of vaccinating 90% of girls against HPV, and this requires a robust understanding of barriers to vaccine uptake. Using a household survey in three communities of Malawi with parents/guardians of girls aged 9-13 years, we collected and analyzed data about intervention-amenable factors hypothesized to be associated with girls' HPV vaccination status. The 299 parent/guardian respondents provided information on 382 girls aged 9-13 years, of whom 39.0% (n = 149) had received ≥ 1 dose of the HPV vaccine. More than half of parents/guardians were concerned about the HPV vaccine's safety. Greater HPV vaccine hesitancy was associated with having an unvaccinated daughter in adjusted multilevel models (aOR 0.69 [95% CI 0.50-0.93]). Higher odds of being vaccinated were found among daughters of respondents with greater knowledge about the HPV vaccine and who knew someone who had cervical cancer. Speaking with more people about cervical cancer/HPV vaccination, and perceiving that other parents are vaccinating their daughters against HPV, were strongly associated with daughters' HPV vaccination status (aOR 2.03 [95% CI 1.59-2.62] and 3.68 [95% CI 1.97-7.18, respectively). Most parents/guardians had not experienced, or did not anticipate experiencing, challenges accessing HPV vaccination services, but those who did also had daughters with lower odds of vaccination. Interventions that leverage social networks and norms, increase confidence in the vaccine's safety, and work to improve access to HPV vaccination services, may increase coverage of the HPV vaccine in Malawi.

IntroductionFor persons failing on dolutegravir- and protease inhibitor-based antiretroviral therapy (ART) regimens, Malawi’s HIV program requires confirmation of HIV drug resistance (HIVDR) before switching to next-line regimens. Approval of applications for HIVDR testing is determined by a national HIVDR committee that also provides management recommendations based on HIVDR test results. We audited HIVDR test applications for all ages in Malawi’s national ART program to evaluate the HIVDR testing process and explore short-term outcomes, including viral suppression.MethodsWe conducted a retrospective review of routinely collected data from applications for HIVDR testing registered between July 2020 and December 2021. We determined drop-offs at steps of the HIVDR testing cascade: approval for genotyping, sample collection, receiving results, completion of genotypic sequencing, provision of management recommendations and implementation of recommendations. We assessed ART outcomes, including the first viral load (VL) result ≥6 months after recommendations from the HIVDR committee.Results228 HIVDR applications were received, of which 75% (172/228) were approved. Of these, 72% (124/172) had samples sent to laboratory and 122 genotyping results were obtained. 75% (92/122) of samples were successfully sequenced and 68% (65/92) sequences had ≥1 major drug resistance-associated mutation, including 17% with moderate or high-level dolutegravir resistance of individuals on dolutegravir-based regimens. Treatment outcomes were available for 90 clients: 65 were alive on ART, 3 had defaulted, 12 died, 9 transferred out and 1 stopped ART. Of 68 available follow-up VL results, 34 (51%) were <1,000 copies/mL.ConclusionsThis audit demonstrates gaps in Malawi’s HIVDR testing cascade and concerning clinical outcomes among those with follow up results: considerable attrition from care and low VL suppression. These results suggest that improvements in HIVDR testing in the Malawi HIV program need to be considered, including in-country sequencing and more efficient procedures for applications, approvals, clinical recommendations and clinical follow up.

BACKGROUND:Cervical cancer screening is an essential public health intervention, and critical to meeting the Global Strategy for Cervical Cancer Elimination goals - yet most women in low- and middle-income countries are never screened. There is a need to understand context-specific factors that facilitate or prevent women from engaging in screening. METHODS:This analysis leverages data collected in 2022-2023 from a national mobile phone-based survey in Kenya and from a household survey conducted in three districts of Malawi. Informed by the Health Belief Model, we assess whether women's reported cervical cancer screening history (ever or never screened) was associated with their perceived susceptibility (awareness of cervical cancer risk factors), perceived severity (knowing someone who was affected by cervical cancer), perceived barriers (access to services), perceived benefits (trust in information about cervical cancer prevention), self-efficacy (engagement in other preventive health behaviors), and cues to action (speaking with others about cervical cancer prevention). RESULTS:Ever-screening for cervical cancer was reported by 49.7% of the 736 Kenyan respondents and 42.5% of the 261 Malawian respondents. There were few associations between women's demographic or socioeconomic characteristics and screening history. The strongest associations were seen for cues to action (women who had spoken about cervical cancer with health workers had 1.88 the adjusted risk ratio for screening in Kenya [95% CI 1.59, 2.24] and 1.89 the adjusted risk in Malawi [95% CI 1.41, 2.54] compared to women who never had these conversations); and for knowing someone who had, or who had died due to, cervical cancer (aRR 1.34 and 1.30 respectively in Kenya, and aRR 2.03 and 1.46 respectively in Malawi). In both countries, self-efficacy was also associated with screening, as was perceived severity in both countries (i.e., knowing someone who had, or who had died due to cervical cancer, which was reported by many Kenyan and Malawian respondents). In Kenya, knowledge of cervical cancer risk factors was also associated with women's screening history, as was access to other preventive health services in Malawi. CONCLUSIONS:These results suggest promising areas for interventions aiming to increase cervical cancer screening in these contexts: encouraging health workers to discuss screening with eligible women, leveraging women's peers who have been affected by cervical cancer, and promoting screening during other preventive health services.

INTRODUCTION:There are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents. METHODS:This pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots. RESULTS:Of the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions. CONCLUSIONS:Daily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.

BACKGROUND:Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS:A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. RESULTS:Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. CONCLUSIONS:Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.