AIDS最新文献

Objective: Examine the association between markers of inflammation in the cerebrospinal fluid (CSF) and neurocognitive impairment (NCI) among diverse persons with HIV (PWH).

Background: Latino PWH are at higher risk for NCI than non-Latino White PWH (NLW). Evidence of inflammation in cerebrospinal fluid (CSF) can be higher among racial and ethnic minority PWH and has been linked to NCI.

Methods: We performed a retrospective cross-sectional analysis of 363 PWH who identified as Latinos or NLW. Neurocognitive performance was measured by a comprehensive battery. A focused panel of biomarkers [interleukin-6 (IL-6), soluble CD14 (sCD14), interferon-γ-inducible protein-10 (IP-10), neurofilament light chain (NFL)] was measured in CSF by immunoassay. Covariates included demographic, HIV disease, medical, psychiatric, and substance use characteristics.

Results: The cohort consisted of 126 Latinos and 237 NLW (age: M = 42.5, SD = 11.0, 88% male, 51.5% AIDS history; 64% on antiretroviral therapy). Latinos had significantly higher NFL levels than NLW (P < 0.0001, adjusted Cohen's d 1.15), but not among virally-suppressed PWH. In the entire cohort, higher sCD14 was associated with NCI (adjusted odds ratio (aOR) = 2.6, confidence interval (CI) = 1.1-6.5] after adjusting for statistically significant covariates.

Conclusions: We did not identify a relationship between ethnicity, inflammation and NCI in this cohort. Future studies might examine sociocultural factors leading to increased inflammation in the CSF in diverse PWH.

Objectives: To determine the impact of increased long-acting injectable antiretroviral therapy (Cabotegravir-rilpivirine [CAB/RPV]) use among persons with diagnosed HIV (PWDH) with viral suppression (VLS), per 2021 US Food and Drug Administration (FDA) guidelines, on HIV incidence and levels of VLS in the US.

Methods: We used the HOPE compartmental model to simulate CAB/RPV use during 2023-2035. We first simulated a baseline scenario (no CAB/RPV), in which 69% of PWDH had VLS. We then introduced CAB/RPV in 2023 under two scenarios: (1) where CAB/RPV improved the duration of VLS post-cessation of ART use compared to oral ART; (2) where CAB/RPV additionally improved adherence. We compared cumulative 2023-35 incidence and percentage of PWDH with VLS at year-end 2035 to baseline.

Results: When CAB/RPV increased the duration of VLS only, cumulative incidence was reduced up to 9%, and VLS increased up to 4%. When CAB/RPV also improved ART adherence, incidence was reduced up to 19.5%, and VLS increased up to 9%.

Conclusions: CAB/RPV, even if only used among PWDH with VLS, may reduce HIV incidence and increase VLS, due to longer-lasting VLS post-cessation of usage. If CAB/RPV also improves ART adherence, incidence is further reduced. Improved clinical efficacy of CAB/RPV may translate to improved population-level outcomes, even in limited use cases.

Objectives: To estimate the probability of long-term nonprogression (LTNP) in the absence of antiretroviral treatment (ART) in children with perinatally acquired HIV, and the impact of LTNP definitions on these estimates.

Design: Analysis of longitudinal routine care data (follow-up to 2016) collected through a collaboration of cohorts of children in routine HIV care across Europe and Thailand.

Methods: LTNP was defined as reaching age 8 years without disease progression (defined as an AIDS diagnosis or immunosuppression based on WHO immunosuppression-for-age thresholds, age-adjusted CD4+z-scores or CD4+ counts). ART initiation was treated as a competing risk (children initiating ART before age 8 were not considered to have LTNP). We included children born domestically in six national HIV cohorts (n = 2481). Additional analyses included domestic-born children enrolled in national cohorts in infancy (aged <12 months, n = 1144, six cohorts), or all domestic-born children in national and nonnational cohorts (n = 4542, 18 cohorts). Results were stratified by birth year.

Results: Among children born domestically in national cohorts in 2004-2007, the probability [95% confidence interval (CI)] of LTNP at age 8 years was 10% (6-15%) based on WHO immunosuppression-for-age criteria. This was lower for children born earlier when ART use was less frequent. Results were similar using other immunosuppression thresholds. Estimates were lower when restricted to domestic-born children in national cohorts enrolled in infancy, and higher when including all domestic-born children.

Conclusion: Up to 10% of children born during 2004-2007 had LTNP at age 8. Our findings may help identify participants with LTNP for research into posttreatment control and HIV cure.

Background: Long-acting injectable cabotegravir-rilpivirine (CAB/RPV-LA) is a promising treatment alternative for people with HIV (PWH) who face adherence challenges with oral antiretroviral therapy (ART). While its clinical efficacy is well-documented, cost-effectiveness data from real-world settings remain limited.

Objective: To evaluate the incremental first-year cost and cost-effectiveness of CAB/RPV-LA versus standard of care (SoC) oral ART among PWH with adherence challenges, from the perspective of a healthcare payer.

Methods: A cohort of 59 PWH initiating CAB/RPV-LA at Ward 86, a San Francisco-based clinic, was analyzed. Viral suppression (VS) rates and treatment costs were compared between CAB/RPV-LA and SoC ART. Cost-effectiveness was assessed using incremental cost per newly virally-suppressed PWH and net monetary benefit (NMB). Sensitivity analyses were performed to evaluate parameter uncertainty.

Results: CAB/RPV-LA achieved a VS rate of 92%, compared to an estimated 15% with SoC ART. The estimated first-year cost of CAB/RPV-LA delivery was $67,041 per patient versus $50,668 for SoC. The incremental cost per newly virally-suppressed PWH was $21,264. CAB/RPV-LA is the most cost-effective option at any willingness-to-pay above this level. The NMB was $243,721 suggesting favorable cost-effectiveness. Sensitivity analyses confirmed the robustness of these results.

Conclusions: Initiating CAB/RPV-LA for PWH with viremia suggests highly favorable cost-effectiveness. Results are sensitive to the costs of antiretroviral drugs, but not to variations in personnel costs or rates of viral suppression within plausible input ranges.

Objective: To investigate bone density accrual over 1 year among peripubertal children living with HIV (CWH) compared to children without infection (CWOH); and risk factors associated with bone density accrual among CWH.

Design: A prospective cohort study in urban Zimbabwe.

Methods: CWH on antiretroviral therapy aged 8-16 years, and CWOH, frequency-matched by age were recruited in Zimbabwe. Z -scores for height-adjusted total-body less-head bone mineral content for lean mass (TBLH-BMC LBM ) and size-adjusted lumbar spine bone mineral apparent density (LS-BMAD) were calculated from dual X-ray absorptiometry (DXA) scan measurements. Linear regression compared bone density accrual by HIV status.

Results: Of 609 participants, 492 (80.7%) completed a follow-up visit (50.2% male, 49.6% CWH). Mean baseline age was 12.5 years. More female CWH than CWOH were in Tanner stages I/II at baseline. Bone density accrual (Δ) adjusted for age, Tanner stage and baseline DXA Z -score was less in male CWH than male CWOH {adjusted mean (95% confidence interval (CI)] ΔLS-BMAD Z -score -0.14 (-0.25 to -0.02) vs. 0.01 (-0.09 to 0.12), P  = 0.020, and ΔTBLH-BMC LBMZ -score -0.19 (-0.33 to -0.04) vs. 0.07 (-0.07 to 0.20), P  = 0.015}, but similar in females with and without HIV [ΔLS-BMAD Z -score 0.05 (-0.07 to 0.17) vs. -0.01 (-0.09 to 0.07), P  = 0.416, and ΔTBLH-BMC LBMZ -score 0.08 (-0.07 to 0.22) vs. -0.03 (-0.12 to 0.07), P  = 0.295]. Viral load greater than 1000 copies/ml and tenofovir disoproxil fumarate use were associated with less gain in LS-BMAD Z -score among males, whereas Tanner stage IV and V were associated with greater gains in LS-BMAD and TBLH-BMC LBMZ -scores among CWH.

Conclusion: Among males only, CWH had impaired bone accrual, associated with high viral load and tenofovir use. Bone density gains were greater in later puberty among CWH suggesting potential to correct deficits.

Objective: To assess efficacy, safety and pharmacokinetics (PK) of oral lenacapavir (LEN) when used as oral bridging (OB) between delayed subcutaneous (SC) LEN injections.

Design: Posthoc analysis of participants in two clinical trials of SC LEN for HIV-1 treatment who required OB when LEN SC dosing was interrupted.

Methods: Oral LEN [300 mg once weekly (QW)] was initiated within 2 weeks of the next scheduled injection (dosing interval: 26 weeks). Efficacy, safety, and PK were assessed every 10-12 weeks.

Results: Overall, 139 participants received ≥1 dose of oral 300 mg QW LEN plus other antiretrovirals. Median duration of OB was 19 weeks in both clinical trials. By missing = excluded analysis, over 95% of participants maintained virologic suppression (HIV-1 RNA <50 copies/ml) at Weeks 10, 20, and 30. Treatment-emergent AEs (TEAEs) were similar to those with SC LEN (excluding injection site reactions). No Grade ≥3 or serious TEAEs were considered related to oral LEN. Throughout OB, mean LEN plasma concentrations and lower bound 90% confidence intervals (CIs) were consistently above inhibitory quotient 4 (4-fold in-vitro protein binding-adjusted 95% effective concentration). OB adherence (by pill count) was ≥95% in the majority of participants in both clinical trials.

Conclusions: High rates of virological suppression were maintained during OB. Oral 300 mg QW LEN was well tolerated and provided adequate plasma concentrations to bridge SC LEN dosing. This analysis supports using 300 mg QW LEN for OB when SC LEN treatment is interrupted.

Objective: This study aimed to identify age-specific cofactors of nonretention among adolescents and young adults living with HIV (AYLHIV) ages 10-24.

Design: This analysis used data from the Data-Informed Stepped Care study (DiSC; NCT05007717), a cluster randomized clinical trial in 24 health facilities in Western Kenya.

Methods: During 12-month follow-up, youth-reported cofactors of missed visits and loss-to-follow-up (LTFU; did not return to clinic within study period) were assessed using generalized linear and mixed effect models and stratified by gender and age.

Results: Among 1904 AYLHIV, median age was 17 years (interquartile range 14-19), and 57.9% were female. A higher proportion of missed visits was observed in older ages (10-14: 6.0%; 15-19: 7.9%; 20-24: 12.5%). Overall, higher resilience (PR = 0.93) and satisfaction with clinic (PR = 0.81) were associated with lower risk of missed visits. Among males, satisfaction with clinic was associated with lower risk (PR = 0.61) while higher stigma was associated with increased risk (PR = 1.31). Among females, resilience was associated with lower risk (PR = 0.93). Having no living parents was associated with higher LTFU risk (PR = 2.24). Among males, horizontal transmission was associated with higher risk (PR = 2.98) and resilience with lower risk (PR = 0.76). Females who came to clinic alone had lower risk of LTFU (PR = 0.27). Age-stratified analyses did not identify additional cofactors.

Conclusions: In this large multisite cohort, older AYLHIV had the most retention challenges. Resilience, satisfaction with clinical care, and stigma exerted an influential role, but cofactors differed between age and gender strata, underscoring the heterogeneity of AYLHIV and suggesting need for tailored approaches.

Objective: To summarize antiretroviral therapy (ART) use in the setting of end-stage kidney disease (ESKD).

Design: Cross-sectional analysis.

Methods: Descriptive analysis of ART regimens and dose of nucleoside/nucleotide reverse-transcriptase inhibitors (NRTI) in people with HIV and ESKD (dialysis, kidney transplantation, or estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m 2 ) receiving HIV and renal care at five London centres. Exposures of interest were use of dual/unboosted ART regimens and higher than recommended doses of renally-cleared NRTI.

Results: A total of 157 participants were included (median age 55 years, 66% male, 84% black ethnicity, median CD4 cell count 382 cells/mm 3 , 99% HIV RNA <200 copies/mL). Fifty-eight (37%) were on dual/unboosted ART regimens, mainly dolutegravir/lamivudine. Participants on dual/unboosted ART had similar rates of HIV suppression as those on triple-ART. Two participants currently virologically controlled on triple-ART had previously failed to suppress on dual/unboosted ART (dolutegravir/rilpivirine and dolutegravir/lamivudine [50 mg]). Lamivudine doses were higher than recommended in 75 (77%) and lower than recommended in 8 (8%) participants. Full dose lamivudine (300 mg daily) was used by 24 (32%) participants with eGFR <30 mL/min/1.73m 2 . None of those currently on reduced-dose lamivudine had required dose reductions for previous toxicity concerns.

Conclusions: Dual/unboosted ART regimens such as dolutegravir/lamivudine provide robust viral efficacy in the setting of ESKD, and higher than recommended, including full-dose, lamivudine was well tolerated. The dolutegravir/lamivudine (300 mg) fixed-dose combination provides a single-tablet regimen for use across the eGFR spectrum, avoids under-exposure to lamivudine, and merits further evaluation in this population.

Objective: Assess virological failures, analyze the results of resistance testing (RET), and investigate factors associated with acquired drug resistance mutations (aDRM).

Design: A retrospective longitudinal cohort study.

Methods: Virological failures (viral load >50 copies/ml) from a cohort of 1130 individuals, diagnosed with HIV-1 in 2010-2018 and followed up until 2020, were included. Demographic, clinical, and virological data were collected. A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM.

Results: Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010-2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4+ levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes (P = 0.039). Diagnoses with CD4+ cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51-7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11-0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13-0.86, P = 0.022) had a significant and persistent relative effect on aDRM.

Conclusion: The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4+ cell counts and AIDS is associated with detection of aDRM.

Objective: To investigate physical, psychosocial and sexual health outcomes in ≥50 years-old people with and without HIV.

Design: Cross-sectional study in Denmark comparing health outcomes by HIV status.

Methods: Data were drawn from the SHARE study, a nationwide survey conducted between 2021 and 2022, examining psychosocial, sexual and reproductive health in people with HIV (PWH), and compared to data from people without HIV (PWOH) in the nationally representative Project SEXUS cohort study. Health outcomes were assessed using validated patient-reported outcome measures, with sex-stratified logistic regression models adjusting for sociodemographic and other confounding factors.

Results: The study included 322 men and 67 women with HIV and 15 548 men and 13 926 women without HIV. PWH were more likely to report being single and having non-Danish parentage. HIV was associated with higher odds of liver disease in both men and women, cardiovascular and lung diseases in men, and osteoporosis and hypertension in women. Compared with PWOH, men with HIV more often reported depressive symptoms or a history of treatment for anxiety, while women with HIV more often reported loneliness, suicidal thoughts and domestic abuse. Sexually, PWH more often reported reduced sexual desire and activity, men with HIV more often reported erectile dysfunction or orgasmic dysfunction and women with HIV more often reported lubrication dysfunction or genital pain dysfunction.

Conclusions: PWH aged ≥50 years in Denmark face significantly more physical, psychosocial and sexual health challenges than PWOH. Clinical attention to these disparities is crucial for improving the overall health of ageing PWH.