AIDS

doi: 10.1097/qad.0000000000003878pmid: 38427596

Background: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. Methods: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan–Meier survival probabilities and Cox proportional hazards ratios were estimated. Results: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82–0.88] and lower overall survival (0.89; 95% CI 0.86–0.91) versus term birth (0.96; 95% CI 0.95–0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54–0.73) and low overall survival (0.66; 95% CI 0.56–0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21–4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03–0.08) compared with not breastfeeding. Conclusion: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.

doi: 10.1097/qad.0000000000003888pmid: 38507584

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.

Objective: People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics. Design: Multicenter cohort study. Methods: Fibrosis progression was defined as development of significant fibrosis [liver stiffness measurement (LSM) ≥8 kPa], or transition to cirrhosis (LSM ≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM less than 8 kPa, or to LSM less than 13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multistate Markov model was used to describe transitions across fibrosis states. Results: Among 1183 PWH included from three centers (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4 and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9–3.5), the incidence rate of fibrosis progression and regression was 2.8 [95% confidence interval (CI) 2.3–3.4] and 2.2 (95% CI 1.9–2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression [odds ratio (OR) 3.11, 95% CI 1.59–6.08], whereas weight gain (OR 0.30, 95% CI 0.10–0.84) and male sex (OR 0.32, 95% CI 0.14–0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain [adjusted hazard ratio (aHR) 3.12, 95% CI 1.41–6.90] and MASLD (aHR 2.72, 95% CI 1.05–7.02). Conclusion: Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy.

Objective: We developed the Healthy Families-PrEP intervention to support HIV-prevention during periconception and pregnancy. We evaluated preexposure prophylaxis (PrEP) use with three objective measures. Design: This single-arm intervention study enrolled women in KwaZulu-Natal, South Africa, who were HIV-uninfected, not pregnant, in a relationship with a partner with HIV or unknown-serostatus, and with pregnancy plans. PrEP was offered as part of a comprehensive HIV prevention intervention. Participants were followed for 12 months. Methods: We evaluated periconception PrEP uptake and adherence using quarterly plasma tenofovir concentrations. We modeled factors associated with PrEP uptake and high plasma tenofovir (past day dosing). Patterns of use were analyzed using electronic pillcap data. Dried blood spots to measure intracellular tenofovir product (past 2 months dosing) were analyzed for a subset of women. Results: Three hundred thirty women with median age 24 (IQR: 22–27) years enrolled. Partner HIV-serostatus was unknown by 96% (N = 316); 60% (195) initiated PrEP. High plasma tenofovir concentrations were seen in 35, 25, 22, and 20% of samples at 3, 6, 9, and 12 months, respectively. Similar adherence was measured by pillcap and dried blood spots. In adjusted models, lower income, alcohol use, and higher HIV stigma were associated with high plasma tenofovir. Eleven HIV-seroconversions were observed (incidence rate: 4.04/100 person-years [95% confidence interval: 2.24–7.30]). None had detectable plasma tenofovir. Conclusion: The Healthy Families-PrEP intervention supported women in PrEP use. We observed high interest in periconception PrEP and over one-third adhered to PrEP in the first quarter; one-fifth were adherent over a year. High HIV incidence highlights the importance of strategies to reduce HIV incidence among periconception women. Clinical Trial Number: NCT03194308

doi: 10.1097/qad.0000000000003933pmid: 38788210

Objective: We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH). Design: Prospective observational cohort study. Methods: PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those <45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1 : 2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses and cytokine responses up to 180 days post-vaccination. Results: Forty PWH received mRNA-1273.214 (N = 35) or BNT162b2 (N = 5) following mRNA-based (N = 29) or vector-based (N = 11) primary vaccination. PWH were predominantly male (87% vs. 26% of non-PWH) and median 57 years [interquartile range (IQR) 53–59]. Their median CD4+ T-cell count was 775 (IQR 511–965) and the plasma HIV-RNA load was <50 copies/ml in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH [4.48, 95% confidence interval (CI) 3.24–6.19] and non-PWH (4.07, 95% CI 3.42–4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. Interferon-γ, interleukin (IL)-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH. Conclusion: A bivalent BA.1 booster vaccine was immunogenic in well treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH.

doi: 10.1097/qad.0000000000003892pmid: 38507583

Objective: The aim of this study is to describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally acquired HIV (PHIV) aged 18–30 years. Design: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Methods: We estimated overall, sex, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression. T2DM was defined as glycosylated hemoglobin more than 6.5% or based on clinical diagnosis and medication use. Hypercholesterolemia was based on medication use or total cholesterol at least 200 mg/dl. Hypertriglyceridemia was based on medication use or fasting triglyceride at least 150 mg/dl or nonfasting at least 200 mg/dl. Hypertension was based on clinical diagnosis. CKD was defined as estimated glomerular filtration rates less than 90 ml/mi|1.73 m2 for at least 3 months. Results: Cumulative incidence by age 30 and incidence rates from age 18 to 30 (per 100 person-years) were T2DM: 19%, 2.9; hypercholesterolemia: 40%, 4.6; hypertriglyceridemia: 50%, 5.6; hypertension: 22%, 2.0; and CKD: 25%, 3.3. Non-Black women had the highest incidence of hypercholesterolemia and hypertriglyceridemia, Black adults had the highest hypertension incidence, and Black men had the highest CKD incidence. Conclusion: There was a high incidence of five chronic comorbidities among people with PHIV. Earlier screening at younger ages might be considered for this unique population to strengthen prevention strategies and initiate treatment in a timely way.