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Psychosocial factors account for a proportion of the difference in cognitive performance between persons with and without HIV

Objective: To investigate whether psychosocial factors account for a proportion of the difference in cognitive performance between persons with and without HIV. Design: Cross-sectional study of 273 participants (178 persons with HIV) from a low income area of Cape Town, South Africa, Methods: Participants completed comprehensive cognitive testing (7 domains) and 12 psychosocial measures (5 current: income, occupation, assets, accommodation, depressive symptoms, 7 from childhood: assets, quality of education, exposure to childhood trauma and violence, primary caregiver occupation and highest level of education), as well as demographic measures standard in cognition studies (age, sex, years of education). We investigated the HIV association with global cognitive performance after adjustment for standard demographic variables, exploratory psychosocial variables, and balancing characteristics of those with and without HIV using propensity score modelling. Results: Persons with HIV had significantly lower scores than persons without HIV in 8/12 psychosocial variables. Of these, 7/12 significantly predicted global T-score. In unadjusted regression, HIV status was associated with a reduction in global T-score of 3.72 units. Adjustment for standard variables, reduced the effect of HIV on global T score by 26.9% to 2.72, additional adjustment for psychosocial variables reduced by 40.3% to 2.22, and adjustment for propensity scores by 42.7% to 2.13. Conclusions: Persons with HIV in this setting have lower psychosocial indices, both current and in childhood, which are associated with lower cognitive test performance as an adult. This is incompletely mitigated by adjustments for standard demographic variables which risks overestimation of cognitive impairment on a population level.

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The steady-state pharmacokinetics of fixed-dose combination dolutegravir+rilpivirine in hemodialysis

Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics (PK) of FDC DTG+RPV in hemodialysis (HD) has not been previously studied. Design: We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG +RPV in 4 adults without HIV either requiring HD and in 4 matched participants with normal renal function. Methods: All participants received FDC DTG(50mg)+RPV(25mg) daily for 10-14 days with food before undergoing an intensive 24-hour PK evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated UHPLC/MS/MS. Descriptive PK parameters were calculated. Results: The HD and normal renal function participants (each group with 2 men and 2 women) were of similar ages (range, 50-60 years) and body mass index (range, 18.5-34.5 kg/m2). No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The AUC0-τ mean (SD) ratios of HD to normal renal function for DTG and RPV were 1.1 (0.4) and 1.1 (0.9), respectively. The mean (SD) Cmin for DTG and RPV in the HD group were 1033 (252) ng/mL and 49 (18) ng/mL, respectively. Conclusions: HD did not lead to clinically appreciable differential exposures to DTG and RPV. Exposures throughout the dosing interval were greater than the reported protein-binding adjusted IC90 efficacy values for DTG (64 ng/mL) and RPV (12 ng/mL) in all participants. These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in HD.

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Treatment of prehypertension among adults with HIV: a randomized clinical trial

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467

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Open Access
Bone density changes in young women in Uganda using tenofovir-based HIV pre-exposure prophylaxis and depot medroxyprogesterone acetate contraception

Background: Injectable depot medroxyprogesterone acetate (DMPA) is the most common contraceptive choice among young women in Uganda, where HIV burden is high and HIV pre-exposure prophylaxis (PrEP) may be offered. For young women who choose to use both agents concurrently, it is unknown whether they will experience declines in BMD beyond those elicited by either product singly. Methods: From 2018–2022, we conducted a 2-year prospective study with women ages 16–25 years in Kampala, Uganda desiring pregnancy and HIV prevention. Women were provided condoms, injectable DMPA, and/or FTC/TDF, according to their choices and underwent annual dual x-ray absorptiometry (DXA) scans. We used tenofovir-diphosphate (TFV-DP) quantification in dried blood spots and DMPA injection dates to classify exposure. Linear regression models estimated the difference in % BMD change from baseline to month 12 for women using FTC/TDF and DMPA versus women using neither product. Results: Of 499 enrolled women, discontinuation and re-starting of contraception and PrEP was common. Women consistently using neither product (n = 39) experienced BMD increases. Women with consistent use of both products during 1 year (n = 22) experienced an average BMD loss of 1.04% at lumbar spine and hip and 1.77% at femoral neck. These losses were different relative to women who used neither agent: lumbar spine -3.35% (95% CI −5.13%, −1.56%, p = 0.001), total hip −2.24% (95% CI −3.87%, −0.60%, p = 0.009), and femoral neck −1.71% (95% CI −3.73%, 0.31%, p = 0.102). Conclusion: We observed a trend for women with concurrent DMPA and FTC/TDF PrEP use to have 1–3% lower BMD than unexposed women after 12 months.

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Open Access
Multidimensional program for insomnia in a cohort of people with HIV

Objective: Sleep disorders (SD) are prevalent in people with HIV (PWH), but poorly addressed in HIV care. We evaluated the effectiveness of a multidimensional program for SD in an outpatient HIV clinic. Methods: Interventional study in 175 PWH on ART suffering from insomnia. Insomnia severity index (ISI), sleep quality, mood disorders, and well being were assessed at baseline and at month 6 after counseling for sleep hygiene and referral to tailored pharmacological and/or neuropsychological interventions. Participants were classified as fully, partial, and nonadherent (FA–PA–NA) to the interventions. Mixed-effects models and longitudinal paired tests evaluated the impact of adherence to interventions on SD overtime. Results: Participants (male 65.7%, median age 51 years, 95.4% with viral suppression) were referred to psychologist (94.8%), psychiatrist (9.1%), and neurologist (2.8%), and 30.3% and 20.5% had indication to hypo-inducing drugs and psychotherapy/cognitive-behavioral therapy. Seventy-seven participants (44.0%) were NA, 9.1% PA, and 46.8% FA. ISI improved in all, but the strongest effect size was seen in FA (D = 0.89, P < 0.001). Perceived wellness improved only in FA, and hours slept per night increased in all but more relevantly in FA and PA (both P < 0.001). In adjusted models, adherence to the interventions ISI decreased (improve) overtime only in FA (aβ = −1.24, P = 0.005 vs. NA; aβ = −0.71, P = 0.349 for PA vs. NA). Conclusions: The introduction of multidimensional programs for SD can reduce the prevalence and severity of insomnia and improve sleep quality and wellness in PWH. Such approach should be integrated into daily multidisciplinary clinical practice for HIV care.

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