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Background: In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection. Methods: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 – March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB. Results: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]. Conclusion: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women. [ABSTRACT FROM AUTHOR]

Background: Differentiated service delivery (DSD) models are recommended for stable people living with HIV on antiretroviral therapy (ART) but there are few rigorous evaluations of patient outcomes. Methods: Adherence clubs (ACs) are a form of DSD run by community health workers at community venues with 2–4 monthly ART refills and annual nurse assessments). Clinic-based care involves 2-monthly ART refills and 4-monthly nurse/doctor assessments. We compared virologic outcomes in stable adults randomised to ACs at four months post-ART initiation to those randomised to primary health care (PHC) ART clinics through 12 months on ART in Cape Town, South Africa (NCT03199027). We hypothesised that adults randomised to ACs would be more likely to be virally suppressed at 12 months post-ART initiation, versus adults randomised to continued PHC care. We enrolled consecutive adults on ART for 3–5 months who met local DSD ['adherence clubs' (AC)] eligibility (clinically stable, VL<400 copies/mL). The primary outcome was VL<400 copies/mL at 12 months on ART. Results: Between January 2017 and April 2018, 220 adults were randomised (mean age 35 years; 67% female; median ART duration 18 weeks); 85% and 94% of participants randomised to ACs and PHCs attended their first service visit on schedule respectively. By 12 months on ART, 91% and 93% randomised to ACs and PHCs had a VL<400 copies/mL, respectively. In a binomial model adjusted for age, gender, previous ART use and nadir CD4 cell count, there was no evidence of superiority of ACs compared to clinic-based care (RD, -2.42%; 95% CI, -11.23 to 6.38). Findings were consistent when examining the outcome at a threshold of VL <1000 copies/mL. Conclusion: Stable adults referred to DSDs at 4 months post-ART initiation had comparable virologic outcomes at 12 months on ART versus PHC clinics, with no evidence of superiority. Further research on long-term outcomes is required. [ABSTRACT FROM AUTHOR]

Background There are few data on the utility of tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs) to predict future viral load (VL) in postpartum women with HIV on antiretroviral therapy (ART). Methods We conducted a nested case-control study within a trial of postpartum ART delivery strategies. Participants started ART containing tenofovir disoproxil fumarate (TDF) in pregnancy, were <10 weeks postpartum, and had a VL <400 copies/mL. VL and TFV-DP samples were taken every 3–6 months over 24 months. Cases had ≥1 VL ≥20 copies/mL; controls were randomly sampled from women with persistent viral suppression (VS; VL <20 copies/mL). Generalized estimating equations were used to calculate likelihood odds ratios (LORs) for future VL ≥20 copies/mL by TFV-DP concentration at the preceding visit. Results 61 cases and 20 controls contributed 365 DBS-VL pairs (median ART duration, 16 months). Sensitivity and specificity of TFV-DP <700 fmol/punch to detect future viremia were 62.9% (95% CI, 54.7–70.6%) and 89.7% (84.9–93.4%), respectively. Adjusting for age, ART duration, previous VL, and duration between the TFV-DP and VL measures, LORs of viremia for TFV-DP concentrations 350–699 and <350 fmol/punch versus TFV-DP ≥1850 fmol/punch were 3.5 (95% CI, 1.1–10.8; P  = .033) and 12.9 (3.6–46.6; P  < .0001), respectively. Including only samples taken during VS, the LOR of future viremia for TFV-DP concentration <350 fmol/punch versus TFV-DP ≥1850 fmol/punch was 9.5 (1.9–47.0). Conclusions TFV-DP concentrations in DBSs were strongly associated with future viremia and appear useful to identify nonadherence and predict future elevated VL. [ABSTRACT FROM AUTHOR]

Background: Adolescents and youth living with HIV (AYAHIV) have worse HIV outcomes than other age groups, particularly in sub-Saharan Africa (SSA). AYAHIV in SSA face formidable health system, interpersonal- and individual-level barriers to retention in HIV care, uptake of ART, and achievement of viral suppression (VS), underscoring an urgent need for multi-component interventions to address these challenges. This cluster-randomized control trial (cRCT) aims to evaluate the effectiveness and monitor implementation of a community-informed multi-component intervention ("CombinADO strategy") addressing individual-, facility-, and community-level factors to improve health outcomes for AYAHIV.Methods: This trial will be conducted in 12 clinics in Nampula Province, Northern Mozambique. All clinics will implement an optimized standard of care (control) including (1) billboards/posters and radio shows, (2) healthcare worker (HCW) training, (3) one-stop adolescent and youth-friendly services, (4) information/motivation walls, (5) pill containers, and (6) tools to be used by HCW during clinical visits. The CombinADO strategy (intervention) will be superadded to control conditions at 6 randomly selected clinics. It will include five additional components: (1) peer support, (2) informational/motivational video, (3) support groups for AYAHIV caregivers, (4) AYAHIV support groups, and (5) mental health screening and linkage to adolescent-focused mental health support. The study conditions will be in place for 12 months; all AYAHIV (ages 10-24 years, on ART) seeking care in the participating sites will be exposed to either the control or intervention condition based on the clinic they attend. The primary outcome is VS (viral load < 50 copies/mL) at 12 months among AYAHIV attending participating clinics. Secondary outcomes include ART adherence (self-reported and TDF levels) and retention in care (engagement in the preceding 90 days). Uptake, feasibility, acceptability, and fidelity of the CombinADO strategy during implementation will be measured. Trial outcomes will be assessed in AYAHIV, caregivers, healthcare workers, and key informants. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cRCTs.Discussion: The CombinADO study will provide evidence on effectiveness and inform implementation of a novel community-informed multi-component intervention to improve retention, adherence, and VS among AYAHIV. If found effective, results will strengthen the rationale for scale up in SSA.Trial Registration: ClinicalTrials.gov NCT04930367 . Registered on 18 June 2021. [ABSTRACT FROM AUTHOR]

Background Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. Methods Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. Results The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI},.4–5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8–527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. Conclusions DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population. [ABSTRACT FROM AUTHOR]

Background The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1–infected individuals are likely to progress to active disease is unknown. Methods Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations. Results Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly. Conclusions Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons. [ABSTRACT FROM AUTHOR]

Background: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. Results: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity. Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled [ABSTRACT FROM AUTHOR]

Long-term use of antiretroviral therapy (ART) increases the risk of developing lipodystrophy. Few studies from Africa have used longitudinal data to assess the development of lipoatrophy and lipohypertrophy. We use clinical anthropometry and dual-energy X-ray absorptiometry (DEXA) to describe changes in body fat distribution over a 24-month period in individuals initiated on ART. A convenience sample of black South Africans (55 men and 132 women) were recruited and followed for 24 months after commencing ART. Body fat distribution was assessed using anthropometric measurements and DEXA scans at baseline and then at 3, 6, 12, 18, and 24 months after commencing ART. DEXA was also used to estimate abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Women gained more overall weight and more regional fat in all areas analyzed on DEXA scans. Women, not men, experienced a significant increasing trend in trunk fat and a significant decreasing trend in limb fat, when expressed as a percentage of total body fat. In men, the risk of developing lipoatrophy was more than two times greater than that of women, after adjusting for age, baseline body mass index, and ART regimen. Lipohypertrophy occurred similarly in men and women. VAT and SAT increased significantly in men and women, with women gaining considerably more than men. These findings are of great concern as an increased waist circumference is associated with increased mortality in HIV-infected populations. Further investigation is required to understand the mechanisms underlying the sex differences in changes in body fat distribution and its effects on cardiovascular risk. [ABSTRACT FROM AUTHOR]

Cluster-randomized controlled trial The CombinADO study to assess the impact of a combination intervention strategy on viral suppression, antiretroviral therapy adherence, and retention in HIV care among adolescents and young people living with HIV: protocol for a cluster-randomized controlled trial. B Correction to: Trials 22, 956 (2021) b B https://doi.org/10.1186/s13063-021-05943-w b Following the publication of the original article [[1]], we were notified of an error in the statistical analysis section. [Extracted from the article]