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Background: It is unclear how rising obesity among people with HIV (PWH) impacts their risk of type 2 diabetes mellitus (diabetes). We examined associations between HIV, prevalent diabetes and adiposity among South African PWH and their peers without HIV (PWOH)., Methods: HIV status was ascertained by antibody testing. Diabetes was defined as current use of oral hypoglycemics, insulin, and/or HbA1c ≥6.5%. Adiposity was measured by body mass index (BMI), waist circumference and waist-to-height ratio. Their associations were examined using sex-stratified multivariable fractional polynomial generalized linear models, reporting adjusted prevalence and prevalence ratios (adjPR)., Results: The mean age among 1,254 PWH and 4,381 PWOH was 41 years (95%CI 28, 56). The prevalence of diabetes among males was similar between PWH [11.3% (7.1, 15.5)] and PWOH [9.8% (8.5, 11.1); p=0.740]. By contrast, diabetes prevalence was higher among female PWOH [15.7% (14.4, 17.0)] than female PWH [10.5 (8.3, 12.8)%; adjPR: 0.67 (0.51, 0.82); p<0.001]. This difference was accentuated with obesity but reversed with leanness. At BMI ≥25 kg/m 2 , female PWH had lower diabetes prevalence [adjPR: 0.58 (0.41, 0.76); p<0.001] than female PHIV. In contrast, at BMI <18 kg/m 2 , female PWH had higher prevalence [adjPR: 1.72 (-1.53, 4.96); p=0.756] than female PWOH., Conclusion: We found sex-specific differences in the relationship between adiposity and diabetes prevalence by HIV serostatus in South Africa. Notably, females living with obesity and HIV had lower prevalence of diabetes than females living with obesity and without HIV, which may have particular implications for diabetes prevention programs in the region., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis ( Mtb ) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure., Methods: Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A 1c ; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics., Results: We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM., Conclusions: Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: HIV clinical guidelines recommend hypertension detection and management to lower cardiovascular disease risk, but these have not been effectively implemented for people living with HIV (PWH). Addressing this implementation gap requires community-engaged implementation studies focused on addressing implementation barriers specific to the HIV care context., Methods: This protocol describes a type 2 effectiveness-implementation hybrid study conducted in nine primary care clinics in Johannesburg. The study will evaluate the effect of implementation strategies on guideline-recommended blood pressure assessment and management in HIV clinics and the effects of assessment/management on patient blood pressure. A stepped-wedge, cluster randomized study design was used to randomize clinics to the time at which they receive the implementation strategies and patient intervention. The implementation strategies tested include identifying and preparing care champions, changing record systems, conducting ongoing training, providing audit and feedback, and changing the physical structure/equipment. The patient intervention tested includes detection of elevated blood pressure, educational materials, lifestyle modification advice, and medication where needed. Implementation outcomes include adoption, fidelity (co-primary outcome), cost, and maintenance of the blood pressure assessment protocol in participating clinics, while patient outcomes include reach, effectiveness (co-primary outcome), and long-term effects of the intervention on patient blood pressure. These will be assessed via direct observation, study records, staff logs, medical chart reviews, and patient and healthcare worker surveys. To examine effects on the implementation (intervention fidelity) and effectiveness (patient blood pressure changes) co-primary outcomes, we will use the standard Hussey and Hughes model for analysis of stepped-wedge designs which includes fixed effects for both interventions and time periods, and a random effect for sites. Finally, we will examine the costs for the implementation strategies, healthcare worker time, and patient-facing intervention materials, as well as the cost-effectiveness and cost-utility of the intervention using study records, patient surveys, and a time and motion assessment., Discussion: This study will address knowledge gaps around implementation of cardiovascular disease preventive practices in HIV care in South Africa. In doing so, it will provide a dual opportunity to promote evidence-based care in the South African HIV care context and help refine implementation research methods to better serve HIV populations globally., Trial Registration: ClinicalTrials.gov: NCT05846503. Registered on May 6, 2023. https://classic., Clinicaltrials: gov/ct2/show/NCT05846503 ., (© 2024. The Author(s).)

There is a growing population of older people with HIV (PWH) in Uganda. Sleep problems disproportionately affect older people and PWH. This study aimed to estimate correlates of sleep health among older Ugandans (aged ≥ 50 years) with and without HIV, using data from the Quality of Life and Aging with HIV in Rural Uganda Study. We used the Pittsburgh Sleep Quality Index to assess sleep quality, duration, and efficiency. We fitted multivariable linear and logistic regression models to estimate the associations between sleep outcomes and variables selected based on the Senescent Sleep Model: age, HIV serostatus, loneliness, urbanicity, symptoms of depression and anxiety, and perceived stress. Of 556 participants, 271 were PWH and 285 were people without HIV (PWoH). There were no statistically significant differences in sleep outcomes by HIV serostatus. Of the total sample, most reported very good (32.79%) or fairly good sleep quality (49.37%). The mean sleep duration was 6.46 h (SD = 1.74). The mean sleep efficiency was 73.98% (SD = 19.52%) with 36.69% having optimal (≥ 85%) sleep efficiency. A positive depression screen was associated with worse sleep quality (adjusted odds ratio [aOR] = 0.21; 95% CI [0.12, 0.36]), shorter sleep duration (b=-0.44; 95% CI [-0.60, -0.28]), and worse sleep efficiency (aOR = 0.51; 95% CI[0.31, 0.83]). Interventions targeting depression may improve sleep among older Ugandans, independent of HIV serostatus. Longitudinal studies are needed to determine the potential bidirectionality of this relationship and elucidate pathways to support sleep health among older Ugandans., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests

Large randomised studies of new long-acting medications for the prevention and treatment of HIV have shown high effectiveness and acceptability. Although modelling studies indicate these agents could be fundamental in HIV elimination, coordination of their entry into health-care markets is crucial, especially in low-income and middle-income countries with high HIV prevalence, where coordination is low despite UNAIDS flagging that global HIV targets will not be met. Research and implementation projects are tightly controlled by originator pharmaceutical companies, with only a small percentage of eligible people living with or affected by HIV benefiting from these projects. WHO, financial donors, manufacturers, and governments need to consider urgent coordinated action from stakeholders worldwide, akin to the successful introduction of dolutegravir into treatment programmes across low-income and middle-income countries. Without this immediate coordination, large-scale access to long-acting agents for HIV will be delayed, potentially extending into the 2030s. This delay is unacceptable considering the established global HIV targets., Competing Interests: Declaration of interests WDFV receives grants paid to University of the Witwatersrand from the Bill & Melinda Gates Foundation, South African Medical Research Council, National Institutes of Health (NIH), Unitaid, Foundation for Innovative New Diagnostics, Children's Investment Fund Foundation, United States Agency for International Development (USAID), ViiV Healthcare, and Merck; drug donations from Gilead Sciences, ViiV Healthcare, Merck, and Johnson and Johnson; honoraria for educational talks and advisory board membership from Gilead Sciences, ViiV Healthcare, Mylan-Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson and Johnson, Sanofi, and Virology Education; conducts commercial drug studies for Merck and Novo Nordisk; and is a member of the international NIH HIV data safety monitoring board and WHO and Southern African HIV Clinicians Society HIV guideline committees. MG is supported financially by NIH. SLB is a member of the AIDS Vaccine Advocacy Coalition board, a Global Coalition of Tuberculosis Activists fiscal sponsor, and is a member of the Global Public Investment Network and Global Fund Advocate Network steering committees. LJ is financially supported by USAID and the Bill & Melinda Gates Foundation. BH receives grant support from ViiV Healthcare to amFAR. MW's receives support from the Bill & Melinda Gates Foundation to the AIDS Vaccine Advocacy Coalition. KM has received honoraria from Johnson and Johnson. LG-B has received honoraria for advisories to Merck, ViiV Healthcare, and Gilead Sciences; is an unpaid board member for Access to Medicine Foundation, AIDS Vaccine Advocacy Coalition, and International AIDS Vaccine Initiative; and her unit (Desmond Tutu HIV Centre) has received a study drug from ViiV Healthcare and Johnson and Johnson for studies funded by the Bill & Melinda Gates Foundation. AO reports consulting fees for Gilead Sciences, ViiV Healthcare, and Assembly Biosciences; and is Director and Chief Science Officer for Tandem Nano, with patents issued and pending in drug delivery. AP receives grants paid to NEAT ID from NIH, National Heart, Lung, and Blood Institute, the EU (via the VERDI Consortium), Gilead Sciences, ViiV Healthcare, and Merck for commercial drug studies; receives honoraria for educational talks and advisory board membership from Gilead Sciences, ViiV Healthcare, Merck, and Virology Education; is on a data safety monitoring board for MRC–PENTA studies; is a member of the European AIDS Clinical Society and British HIV Association HIV treatment guidelines panels; is the President of NEAT ID; and is a board member of Doctor's with Africa CUAMM UK. PR has received grants from ViiV Healthcare and consulted for Gilead Sciences. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on nonnucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics., Methods: We conducted a prospective cohort study of PWH aged ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24 and 48 weeks later. The primary end point was viral suppression (<200 copies/mL) at 48 weeks. We collected blood for retrospective viral load (VL) assessment and conducted genotypic resistance tests for specimens with VL >500 copies/mL., Results: We enrolled 500 participants (median age 47 years; 41% women). At 48 weeks after TLD transition, 94% of participants were in care with a VL <200 copies/mL (n = 469/500); 2% (n = 11/500) were lost from care or died; and only 2% (n = 9/500) had a VL >500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events., Conclusions: High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region., Clinical Trials Registration: NCT04066036., Competing Interests: Potential conflicts of interest. V. C. M. received investigator-initiated research grants and consultation fees from Eli Lilly, Bayer, Gilead Sciences, Merck, and ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

It remains unclear if and how body mass index (BMI) levels have changed over time in HIV endemic regions. We described trends in mean BMI and prevalence of overweight between 2003-2019 in 10 countries in Africa including people living with (PLWH) and without (PLWoH) HIV. We pooled Demographic and Health Surveys (DHS) from countries where ≥2 surveys >4 years apart were available with height/weight measurements and HIV tests. HIV status was ascertained with a finger-prick dried blood spot (DBS) specimen tested in a laboratory. The DBS is taken as part of the regular DHS procedures. We summarized age and socioeconomic status standardized sex-specific mean BMI (kg/m2) and prevalence of overweight (BMI ≥25 kg/m2) by HIV status. We fitted country-level meta-regressions to ascertain if changes in ART coverage were correlated with changes in BMI. Before 2011, women LWH (22.9 [95% CI: 22.2-23.6]) and LWoH (22.6 [95% CI: 22.3-22.8]) had similar mean BMI. Over time, mean BMI increased more in women LWH (+0.8 [95% CI: 0.7-0.8] BMI units) than LWoH (+0.2 [95% CI: 0.2-0.3]). Before 2013, the mean BMI was similar between men LWH (21.1 (95% CI: 20.3-21.9)) and LWoH (20.8 (95% CI: 20.6-21.1)). Over time, mean BMI increased more in men LWoH (+0.3 [95% CI: 0.3-0.3]) than LWH (+0.1 [95% CI: 0.1-0.1]). The same profile was observed for prevalence of overweight. ART coverage was not strongly associated with BMI changes. Mean BMI and prevalence of overweight were similar in PLWH and PLWoH, yet in some cases the estimates for PWLH were on track to catch up with those for PLWoH. BMI monitoring programs are warranted in PLWH to address the rising BMI trends., Competing Interests: VCM has received investigator-initiated research grants (to the institution) and consultation fees from Eli Lilly, Bayer, Gilead Sciences, Merck, and ViiV., (Copyright: © 2024 Carrillo-Larco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of nirmatrelvir-ritonavir near the time of symptom onset, coupled with incomplete viral clearance, appear to be the main factors leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. Finally, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment, in particular to a 10-day regimen, may greatly diminish the risk for rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2., Competing Interests: Competing interests: ASP owns stock in Pfizer. He was also on a Pfizer advisory committee and received an honorarium. The other authors declare that they have no competing interests.

Importance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood., Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound., Design, Setting, and Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023. Participants were divided into those who received antiviral therapy and those who did not. The study was conducted at a multicenter health care system in Boston, Massachusetts., Exposure: Treatment regimen, including none, nirmatrelvir, and remdesivir., Main Outcomes and Measures: The primary outcome was emergent SARS-CoV-2 antiviral resistance, defined as the detection of antiviral resistance mutations, which were not present at baseline, were previously associated with decreased antiviral efficacy, and emerged during or after completion of a participant's treatment. Next-generation sequencing was used to detect low frequency mutations down to 1% of the total viral population., Results: Overall, 156 participants (114 female [73.1%]; median [IQR] age, 56 [38-69] years) were included. Compared with 63 untreated individuals, the 79 who received nirmatrelvir were older and more commonly immunosuppressed. After sequencing viral RNA from participants' anterior nasal swabs, nirmatrelvir resistance mutations were detected in 9 individuals who received nirmatrelvir (11.4%) compared with 2 of those who did not (3.2%) (P = .09). Among the individuals treated with nirmatrelvir, those who were immunosuppressed had the highest frequency of resistance emergence (5 of 22 [22.7%]), significantly greater than untreated individuals (2 of 63 [3.1%]) (P = .01). Similar rates of nirmatrelvir resistance were found in those who had virologic rebound (3 of 23 [13.0%]) vs those who did not (6 of 56 [10.7%]) (P = .86). Most of these mutations (10 of 11 [90.9%]) were detected at low frequencies (<20% of viral population) and reverted to the wild type at subsequent time points. Emerging remdesivir resistance mutations were only detected in immunosuppressed individuals (2 of 14 [14.3%]) but were similarly low frequency and transient. Global Initiative on Sharing All Influenza Data analysis showed no evidence of increased nirmatrelvir resistance in the United States after the authorization of nirmatrelvir., Conclusions and Relevance: In this cohort study of 156 participants, treatment-emergent nirmatrelvir resistance mutations were commonly detected, especially in individuals who were immunosuppressed. However, these mutations were generally present at low frequencies and were transient in nature, suggesting a low risk for the spread of nirmatrelvir resistance in the community with the current variants and drug usage patterns.

Background: The relationship between HIV and frailty, a predictor of poor outcomes in the face of stressors, remains unknown in older people in sub-Saharan Africa., Methods: We analysed data from the Quality of Life and Ageing with HIV in Rural Uganda cohort study to estimate the prevalence and correlates of frailty among older people with HIV (PWH) on long-term antiretroviral therapy and among age and sex-similar HIV-uninfected comparators. Frailty was defined as a self-report of 3 or 4 (and pre-frailty as 1 or 2) of the following phenotypic variables: weight loss, exhaustion, low activity, and slowness. We estimated the prevalence of frailty and pre-frailty and fitted logistic regression models to estimate the association between HIV and frailty, adjusting for sociodemographic factors, depression, and other comorbidities., Results: We enrolled 599 participants (49% women) with a mean age of 58 years. PWH had a similar prevalence of frailty (8.1% vs. 10.9%, p=0.24) but a lower prevalence of pre-frailty (54.2% vs. 63.2%, p=0.03) compared with their HIV-uninfected comparators. In multivariable regression models, people with depression (AOR 7.52 [95% CI: 3.67-15.40], p<0.001) and those with ≥1 comorbidities (AOR 3.15 [95% CI: 1.71-3.82], p<0.001) were more likely to be frail. HIV serostatus was not significantly associated with frailty (AOR 0.71 [95% CI: 0.37-1.34], p=0.29)., Conclusion: Older PWH had a similar prevalence of frailty as those without HIV. These findings call for additional study of the factors that contribute to the robustness of older PWH in sub-Saharan Africa., Competing Interests: Conflict of Interest and Source of Funding All authors declare no competing interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The burden of hypertension among people with HIV is high, particularly in low-and middle-income countries, yet gaps in hypertension screening and care in these settings persist. This study aimed to identify facilitators of and barriers to hypertension screening, treatment, and management among people with HIV in primary care clinics in Johannesburg, South Africa. Additionally, different stakeholder groups were included to identify discordant perceptions., Methods: Using a cross-sectional study design, data were collected via interviews (n = 53) with people with HIV and hypertension and clinic managers and focus group discussions (n = 9) with clinic staff. A qualitative framework analysis approach guided by COM-B and the Theoretical Domains Framework were used to identify and compare determinants of hypertension care across stakeholder groups., Results: Data from clinic staff and managers generated three themes characterizing facilitators of and barriers to the adoption and implementation of hypertension screening and treatment: 1) clinics have limited structural and operational capacity to support the implementation of integrated care models, 2) education and training on chronic care guidelines is inconsistent and often lacking across clinics, and 3) clinicians have the goal of enhancing chronic care within their clinics but first need to advocate for health system characteristics that will sustainably support integrated care. Patient data generated three themes characterizing existing facilitators of and barriers to clinic attendance and chronic disease self-management: 1) the threat of hypertension-related morbidity and mortality as a motivator for lifestyle change, 2) the emotional toll of clinic's logistical, staff, and resource challenges, and 3) hypertension self-management as a patchwork of informational and support sources. The main barriers to hypertension screening, treatment, and management were related to environmental resources and context (i.e., lack of enabling resources and siloed flow of clinic operations) and patients' knowledge and emotions (i.e., lack of awareness about hypertension risk, fear, and frustration). Clinical actors and patients differed in perceived need to prioritize HIV versus hypertension care., Conclusions: The convergence of multi-stakeholder data highlight key areas for improvement, where tailored implementation strategies targeting motivations of clinic staff and capacity of patients may address challenges to hypertension screening, treatment, and management recognized across groups., (© 2024. The Author(s).)

Background: People with HIV (PWH) on integrase inhibitor-based regimens may be at risk of excess weight gain, but it is unclear if this risk is consistent across settings. We assessed weight change over 48 weeks among PWH who were transitioned to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD)., Design: We conducted a prospective cohort study at public-sector HIV clinics in Uganda and South Africa., Methods: Eligible participants were adults who were transitioned to TLD. Weight was measured at enrollment, 24-, and 48-weeks post TLD transition. Our outcomes were weight change, change in waist circumference, and clinically significant weight gain, defined as ≥10% increase in weight from baseline, over 48 weeks. We used linear mixed-effects regression models, adjusted for demographic factors, to estimate weight gain and identify risk factors., Results: Weight data were available for 428 participants in Uganda and 367 in South Africa. The mean weight change was 0.6 kg [95% CI: 0.1-1.0] in Uganda and 2.9 kg [2.3-3.4] in South Africa ( P  < 0.001). The mean change in waist circumference was 0.8 cm [95% CI: 0.0-1.5]) in Uganda and 2.3 cm [95% CI: 1.4-3.2] in South Africa ( P  = 0.012). Clinically significant weight gain occurred in 9.8% [7.0-12.6] of participants in Uganda and 18.0% [14.1-21.9] in South Africa ( P  < 0.001). After adjustment, PWH gained significantly less weight in Uganda than in South Africa., Conclusions: PWH in South Africa experienced significantly greater weight gain and increases in waist circumference compared to Uganda. Strategies to address weight gain in PWH should be carefully considered and may vary by region., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Growing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized., Methods: We analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease., Results: In the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95-1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53-0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87-0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94-0.99)., Conclusions: Among people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population., (© 2024. The Author(s).)

Introduction: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP)., Methods: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI)., Results: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present., Conclusions: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care., Clinical Trial Number: NCT03122262., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: -0.51 (-0.91, -0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined., (© 2024. The Author(s).)

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) study found a 35% reduction in major adverse cardiovascular events for people with human immunodeficiency virus who received daily pitavastatin. However, how this evidence will change practice is far from certain. Here, we outline evidence gaps and political and healthcare delivery challenges that will need to be addressed for REPRIEVE to offer public health benefits in low- and middle-income countries., Competing Interests: Potential conflicts of interest. J. M.-G. reports grants or contracts from GSK Pharmaceuticals and Regeneron Pharmaceuticals and consulting fees from the World Health Organization (WHO). V. C. M. reports grants or contracts from Gilead for ACTT2, ACTT3, and ACTT4, from ViiV for DISCO and ASPIRE, and from CDC/NIH/VA for other studies; participation on a data and safety monitoring board or advisory board for IL-1b inhibitor study, CLEAR HIV, VB201, Outsmart, and ECLIPSE; and a role as study section chair for NIH. M. K. A. reports personal fees outside the scope of this work from Eli Lilly. D. F. reports consulting fees (to institution) as a diabetes consultant for the WHO; career development funding on implementation science for cardiovascular disease prevention (award K23HL161271) from NIH; and service as an unpaid staff physician for the Maya Health Alliance and GlucoSalud (nongovernmental health organizations in Guatemala). W. D. F. V. reports grants or contracts unrelated to this work from the Bill and Melinda Gates Foundation, US Agency for International Development, Unitaid, SA Medical Research Council, Foundation for Innovative New Diagnostics, Children's Investment Fund Foundation, Gilead, ViiV, Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, Virology Education, SA HIV Clinicians Society, and Dira Sengwe. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa., Methods: In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age-stratified mortality hazard ratios: 1.2-2.3 (females)/1.1-1.9 (males) for people with current versus never smoking status; and 1.0-1.3 (females)/1.0-1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non-suppression. In sensitivity analysis, we varied smoking-associated and HIV-associated mortality risks. Additionally, we estimated the total life-years gained if a proportion of all virologically suppressed PWH stopped smoking., Results: Forty-five-year-old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life-years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life-years. Simulated PWH who continue smoking lose more life-years from smoking than from HIV (females, 5.3 vs. 3.0 life-years; males, 3.7 vs. 2.6 life-years). The impact of smoking and smoking cessation increase as smoking-associated mortality risks increase and HIV-associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking-associated mortality hazard ratio; varying this parameter results in 1.0-5.1 life-years gained from cessation at age 45y. If 10-25% of virologically suppressed PWH aged 30-59y in South Africa stopped smoking now, 190,000-460,000 life-years would be gained., Conclusions: Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy., (© 2024. The Author(s).)

Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (<1%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, particularly to rilpivirine (RPV) even in ART-naïve individuals, was concerning. Twenty percent of sequenced individuals belonged to transmission clusters, with geographic analysis highlighting higher clustering in peripheral and rural areas. Our findings suggest promise for INSTI-based strategies in this setting but underscore the need for RPV resistance screening before implementing long-acting cabotegravir (CAB) + RPV. The significant clustering emphasises the importance of geographically targeted interventions to effectively curb HIV-1 transmission., (© 2024. The Author(s).)

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (β = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (β = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Between 2018 and 2022 the Liberian Government implemented the National Community Health Assistant (NCHA) program to improve provision of maternal and child health care to underserved rural areas of the country. Whereas the contributions of this and similar community health worker (CHW) based healthcare programs have been associated with improved process measures, the impact of a governmental CHW program at scale on child mortality has not been fully established. We will conduct a cluster sampled, community-based survey with landmark event calendars to retrospectively assess child births and deaths among all children born to women in the Grand Bassa District of Liberia. We will use a mixed effects Cox proportional hazards model, taking advantage of the staggered program implementation in Grand Bassa districts over a period of 4 years to compare rates of under-5 child mortality between the pre- and post-NCHA program implementation periods. This study will be the first to estimate the impact of the Liberian NCHA program on under-5 mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jockers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health-related quality of life (HRQoL) assesses the perceived impact of health status across life domains. Although research has explored the relationship between specific conditions, including HIV, and HRQoL in low-resource settings, less attention has been paid to the association between multimorbidity and HRQoL. In a secondary analysis of cross-sectional data from the Vukuzazi ("Wake up and know ourselves" in isiZulu) study, which identified the prevalence and overlap of non-communicable and infectious diseases in the uMkhanyakunde district of KwaZulu-Natal, we (1) evaluated the impact of multimorbidity on HRQoL; (2) determined the relative associations among infectious diseases, non-communicable diseases (NCDs), and HRQoL; and (3) examined the effects of controlled versus non-controlled disease on HRQoL. HRQoL was measured using the EQ-5D-3L, which assesses overall perceived health, five specific domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and three levels of problems (no problems, some problems, and extreme problems). Six diseases and disease states were included in this analysis: HIV, diabetes, stroke, heart attack, high blood pressure, and TB. After examining the degree to which number of conditions affects HRQoL, we estimated the effect of joint associations among combinations of diseases, each HRQoL domain, and overall health. Then, in one set of ridge regression models, we assessed the relative impact of HIV, diabetes, stroke, heart attack, high blood pressure, and tuberculosis on the HRQoL domains; in a second set of models, the contribution of treatment (controlled vs. uncontrolled disease) was added. A total of 14,008 individuals were included in this analysis. Having more conditions adversely affected perceived health (r = -0.060, p<0.001, 95% CI: -0.073 to -0.046) and all HRQoL domains. Infectious conditions were related to better perceived health (r = 0.051, p<0.001, 95% CI: 0.037 to 0.064) and better HRQoL, whereas non-communicable diseases (NCDs) were associated with worse perceived health (r = -0.124, p<0.001, -95% CI: 0.137 to -0.110) and lower HRQoL. Particular combinations of NCDs were detrimental to perceived health, whereas HIV, which was characterized by access to care and suppressed viral load in the large majority of those affected, was counterintuitively associated with better perceived health. With respect to disease control, unique combinations of uncontrolled NCDs were significantly related to worse perceived health, and controlled HIV was associated with better perceived health. The presence of controlled and uncontrolled NCDs was associated with poor perceived health and worse HRQoL, whereas the presence of controlled HIV was associated with improved HRQoL. HIV disease control may be critical for HRQoL among people with HIV, and incorporating NCD prevention and attention to multimorbidity into healthcare strategies may improve HRQoL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stanton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease., (© 2024. The Author(s).)

Loneliness among older adults has been identified as a major public health problem. Yet little is known about loneliness, or the potential role of social networks in explaining loneliness, among older people with HIV (PWH) in sub-Saharan Africa, where 70% of PWH reside. To explore this issue, we analyzed data from 599 participants enrolled in the Quality of Life and Ageing with HIV in Rural Uganda study, including older adults with HIV in ambulatory care and a comparator group of people without HIV of similar age and gender. The 3-item UCLA Loneliness Scale was used to measure loneliness, and HIV status was the primary explanatory variable. The study found no statistically significant correlation between loneliness and HIV status. However, individuals with HIV had smaller households, less physical and financial support, and were less socially integrated compared to those without HIV. In multivariable logistic regressions, loneliness was more likely among individuals who lived alone (aOR:3.38, 95% CI:1.47-7.76) and less likely among those who were married (aOR:0.34, 95% CI:0.22-0.53) and had a higher level of social integration (aOR:0.86, 95% CI: 0.79-0.92). Despite having smaller social networks and less support, older adults with HIV had similar levels of loneliness as those without HIV, which may be attributed to resiliency and access to HIV-related health services among individuals with HIV. Nonetheless, further research is necessary to better understand the mechanisms involved., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: ADVANCE compared 3 World Health Organization-recommended first-line regimens in participants with HIV who were antiretroviral naive., Methods: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtricitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks., Results: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm., Conclusions: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

Rapid advances in the potency, safety, and availability of modern HIV antiretroviral therapy (ART) have yielded a near-normal life expectancy for most people living with HIV (PLWH). Ironically, considering the history of HIV/AIDS (initially called "slim disease" because of associated weight loss), the latest dilemma faced by many people starting HIV therapy is weight gain and obesity, particularly Black people, women, and those who commenced treatment with advanced immunodeficiency. We review the pathophysiology and implications of weight gain among PLWH on ART and discuss why this phenomenon was recognized only recently, despite the availability of effective therapy for nearly 30 years. We comprehensively explore the theories of the causes, from initial speculation that weight gain was simply a return to health for people recovering from wasting to comparative effects of newer regimens vs prior toxic agents, to direct effects of agents on mitochondrial function. We then discuss the implications of weight gain on modern ART, particularly concomitant effects on lipids, glucose metabolism, and inflammatory markers. Finally, we discuss intervention options for PLWH and obesity, from the limitations of switching ART regimens or specific agents within regimens, weight-gain mitigation strategies, and potential hope in access to emerging antiobesity agents, which are yet to be evaluated in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa., Methods: In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2-4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods., Results: The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2-3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area., Conclusions: In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Over the past decade, 15 high-priority countries in eastern and southern Africa have promoted voluntary medical male circumcision for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) prevention. The prevalence of male circumcision in Uganda nearly doubled from 26% in 2011 to 43% in 2016, but remains below the 2020 target level. Little is known about how common male circumcision is perceived to be, how accurate such perceptions are, and whether they are associated with men's own circumcision uptake., Methods: We conducted a cross-sectional study of all adult residents of eight villages in Rwampara District, southwestern Uganda in 2020-2022. We elicited their perceptions of the adult male circumcision prevalence within their village: >50% (most men), 10% to <50% (some), <10%, (few to none), or do not know. We compared their perceived norms to the aggregated prevalence of circumcision reported in these villages. We used a modified multivariable Poisson regression model to estimate the association between perceived norms and personal circumcision uptake among men., Results: We surveyed 1566 participants (91% response rate): 698 men and 868 women. Among the men, 167 (27%) reported being circumcised, including 167/444 (38%) men <50 years of age. Approximately one-fourth of the population (189 (27%) men and 177 (20%) women) believed that few to no men in their own village had been circumcised. In a multivariable regression model, men who underestimated the prevalence of male circumcision were less likely to be circumcised themselves (adjusted relative risk (aRR) = 0.51; 95% confidence interval (CI) = 0.37-0.83)., Conclusions: In this population-based study in rural Uganda, one-fourth of men underestimated the prevalence of male circumcision. Men who underestimated the extent of circumcision uptake were themselves less likely to be circumcised. If the observed association is causal and underestimates within the population contribute to low uptake, then interventions correcting these misperceived norms could increase uptake of voluntary medical male circumcision., Competing Interests: Disclosure of Interests: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare that ACT is a member of the Journal of Global Health editorial board and reports receiving a financial honorarium from Elsevier, Inc. for his work as Co-Editor in Chief of the Elsevier-owned journal SSM-Mental Health., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Background: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir-ritonavir (N-R) and virologic rebound (VR)., Objective: To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19., Design: Observational cohort study., Setting: Multicenter health care system in Boston, Massachusetts., Participants: Ambulatory adults with acute COVID-19 with and without use of N-R., Intervention: Receipt of 5 days of N-R treatment versus no COVID-19 therapy., Measurements: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log 10 copies/mL that were also at least 1.0 log 10 copies/mL higher than a prior viral load below 4.0 log 10 copies/mL., Results: Compared with untreated persons ( n = 55), those taking N-R ( n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) ( P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected., Limitations: Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission., Conclusion: Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1756.

Valid screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the WHO's Global Diabetes Compact. We explored anthropometric thresholds to optimally screen and refer individuals for diabetes testing in rural South Africa. We evaluated screening thresholds for waist circumference (WC), body mass index (BMI), and waist-hip ratio (WHR) to detect dysglycemia based on a glycated hemoglobin (HbA1C) ≥6.5% among adults in a population-based study in South Africa using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for this population, and fit models stratified by sex, age, and HIV status. The prevalence of dysglycemia in the total study population (n = 17,846) was 7.7%. WC had greater discriminatory capacity than WHR to detect dysglycemia in men (p-value<0.001) and women (p<0.001). WC had greater discriminatory capacity than BMI to detect dysglycemia in women (p<0.001). However, BMI and WC performed similarly for men (p = 0.589). Whereas traditional WC thresholds for women (>81cm) performed well (sensitivity 91%, positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and PPV among men (traditional >94cm, derived >79.5cm). WC outperforms BMI as an anthropometric screening measure for dysglycemia in rural South Africa. Whereas WC guideline thresholds are appropriate for women, male-derived WC cutoffs performed better at lower thresholds. In this rural South African population, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Castle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Several low-and middle-income countries are undergoing rapid epidemiological transition with a rising burden of non-communicable diseases (NCDs). South Africa (SA) is a country with one of the largest HIV epidemics worldwide and a growing burden of NCDs where the collision of these epidemics poses a major public health challenge., Methods: Using data from a large nationally representative survey, the South Africa Demographic and Health Survey (SADHS 2016), we conducted a geospatial analysis of several diseases including HIV, tuberculosis (TB), cardiovascular, respiratory, and metabolic diseases to identify areas with a high burden of co-morbidity within the country. We explored the spatial structure of each disease and associations between diseases using different spatial and visual data methodologies. We also assessed the individual level co-occurrence of HIV and the other diseases included in the analysis., Results: The spatial distribution for HIV prevalence showed that this epidemic is most intense in the eastern region of the country, mostly within the Gauteng, Mpumalanga, and Kwazulu-Natal provinces. In contrast, chronic diseases had their highest prevalence rates the southern region of the country, particularly in the Eastern and Western Cape provinces. Individual-level analyses were consistent with the spatial correlations and found no statistically significant associations between HIV infection and the presence of any NCDs., Conclusions: We found no evidence of geospatial overlap between the HIV epidemic and NCDs in SA. These results evidence the complex epidemiological landscape of the country, characterized by geographically distinct areas exhibiting different health burdens. The detailed description of the heterogenous prevalence of HIV and NCDs in SA reported in this study could be a useful tool to inform and direct policies to enhance targeted health service delivery according to the local health needs of each community., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.  • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing.  • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions.  • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV., Competing Interests: SJL has received research funding paid to her institution from Gilead Sciences. VC has received travel grants, advisor honorarium and research grant from Merck Sharp & Dohme, ViiV Healthcare and Gilead Sciences. FCS has been a consultant to ViiV Healthcare, Gilead Sciences and Merck Sharp & Dohme, and received research grants paid to her institution from Gilead Sciences. CC has received honoraria and conference travels grants from Merck Sharp & Dohme, Gilead Sciences, and ViiV Healthcare. DD has received honoraria for participation in advisory boards and conference travel grants ViiV Healthcare, Gilead Sciences, Janssen Pharmaceuticals, and Merck Sharp & Dohme. LF has received NIH research grants paid to her institution. RKG has received honoraria for participation on advisory boards from Gilead-Sciences and GlaxoSmithKline. RDK has received research grants from Gilead Sciences paid to his institution. DRK is a consultant to and has received honoraria from AbbVie, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Merck, Roche, and ViiV Healthcare. DRK has also received honoraria from Gilead for expert testimony and speaking fees from Gilead Sciences and Janssen Pharmaceuticals and has received research support paid to his institution from Gilead Sciences, Merck, and ViiV Healthcare. AGM received travel grants, honoraria and study grants from Gilead Sciences, Merck Sharp & Dohme, ViiV Healthcare, GlaxoSmithKline, Roche, and Astra Zeneca. RP has received research grants paid to his institution from Merck Sharp & Dohme and ViiV Healthcare and consulting fees from Gilead Sciences, Merck Sharp & Dohme, GlaxoSmithKline, Atea Pharmaceuticals, Roche, and Shinogi Pharmaceuticals. PCS is a co-founder of, shareholder in, and consultant to Sherlock Biosciences and Delve Bio, and a board member of and shareholder in Danaher Corporation. JMS has received research support, honorarium, or consulting fees from the following: Abbvie, Merck, Gilead Sciences, GlaxoSmithKline, Tibotec-Janssen, Teva, Virology Education and ViiV Healthcare. He has received travel support and stipends for advisory work for the World Health Organization. WS has received speaking honoraria from GlaxoSmithKline, ViiV Healthcare, Merck Sharp & Dohme, Pfizer, and Abbott Pharmaceuticals. AMJW has received research support paid to her institution by Gilead Sciences and has consulted for Gilead Sciences and ViiV Healthcare. JOW receives funding from grants and contracts to his institution from NIH and CDC pertaining to work on HIV molecular epidemiology. HFG has received grants paid to his institution from Gilead Sciences, and Roche, and has received consulting fees from Merck, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, GlaxoSmithKline, Johnson and Johnson, and Novartis. RWS has received honoraria for participation in advisory boards from Gilead Sciences and GlaxoSmithKline and speaking honoraria from Gilead Sciences and ViiV Healthcare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Left ventricular (LV) remodeling and its transitions from compensatory adaptations to LV dysfunction have not been examined in adolescents with perinatally acquired HIV infection (PHIV). We used cardiovascular magnetic resonance (CMR) in a cross-sectional study to characterize PHIV-related progressive LV remodeling in adolescents in South Africa., Methods: Adolescents with PHIV on antiretroviral treatment and their HIV uninfected peers completed 3 T CMR examination. We defined LV remodeling by LV mass/volume (M/V) ratio, modelling progressive LV remodeling as increasing M/V ratio. Linear regression models were applied to estimate the correlates of progressive LV remodeling., Results: Overall, 71 adolescents with PHIV [mean age: 15.2 years; 54% male] and 36 HIV uninfected [15.1 years; 42% male] peers were enrolled. Adolescents with PHIV had lower mean LV M/V ratio (0.68 vs. 0.75 g/mL; p = 0.004) than HIV uninfected peers, without LV hypertrophy in either group. Among adolescents with PHIV, increasing M/V ratio was accompanied by increasing interstitial volume [adjusted mean change (AMC) per 0.1 g/mL M/V ratio: 1.75 mL, p < 0.001] with no change in global circumferential strain (GCS) [AMC per 0.1 g/mL M/V ratio: -0.21%, p = 0.48]. However, in HIV uninfected individuals, increasing M/V ratio was accompanied by increasing peak GCS [AMC per 0.1 g/mL M/V ratio: -1.25%, p = 0.039] with no change in interstitial volume (AMC per 0.1 g/mL M/V ratio: 1.16 mL, p = 0.32]., Conclusions: Successfully treated PHIV is associated with less severe LV remodeling in adolescence when compared to HIV uninfected controls. LV remodeling in PHIV is associated with disproportionate expansion of the non-contractile interstitium not accompanied by improved GCS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Itai M. Magodoro reports financial support was provided by National Institutes of Health. Itai M. Magodoro reports financial support was provided by AIDS Healthcare Foundation. Heather Zar reports financial support was provided by National Institutes of Health. Heather Zar reports financial support was provided by South African Medical Research Council. Mark J. Siedner reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases., Methods: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution., Findings: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis., Interpretation: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority., Funding: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust., Translation: For the isiZulu translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The objective of this study is to explore how HIV care affects health-related quality of life (HRQoL) among older people in Uganda., Methods: We enrolled older-aged (≥49 years) people with HIV receiving HIV care and treatment, along with age- and sex-similar people without HIV. We measured health-related quality of life using the EQ-5D-3L scale., Results: People with HIV ( n  = 298) and people without HIV ( n  = 302) were similar in median age (58.4 vs. 58.5 years), gender, and number of comorbidities. People with HIV had higher self-reported health status ( b  = 7.0; 95% confidence interval [CI], 4.2-9.7), higher EQ-5D utility index ( b  = 0.05; 95% CI, 0.02-0.07), and were more likely to report no problems with self-care (adjusted odds ratio [AOR], 2.0; 95% CI, 1.2-3.3) or pain/discomfort (AOR = 1.8, 95% CI, 1.3-2.8). Relationships between HIV serostatus and health-related quality of life differed by gender, but not age., Conclusions: Older people with HIV receiving care and treatment reported higher health-related quality of life than people without HIV in Uganda. Access to primary care through HIV programs and/or social network mobilization may explain this difference, but further research is needed to elucidate the mechanisms.