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Objectives: Achieving optimal adherence to antiretroviral therapy (ART) and viral suppression is still insufficient for attaining the UNAIDS 95-95-95 target of 2030, especially among adolescents living with HIV (ALWHIV). This study sought to develop a model to predict poor adherence risk among ALWHIV and identify associated risk factors.

Design: We utilized machine learning (ML) to predict future ART adherence among ALWHIV leveraging its ability to analyze complex, multidimensional data.

Methods: We leveraged a dataset from a 6-year (2012-2018) longitudinal randomized control trial (RCT) with 635 ALWHIV in Uganda. We evaluated six ML models and retained one with the highest Area Under Receiver Operating Characteristic (AUROC), and Area Under Precision-Recall Curve (AUPRC). We further identified principal factors associated with ART adherence based on the best model.

Results: The random forest model outperformed others, with mean AUROC: 0·71 (BC 95% CI: [0·69-0·72]) and AUPRC: 0·55 (BC 95% CI: [0·53-0·58]). The principal risk factors of poor adherence were poor adherence history; poverty; biological relationship to caregiver; self-concept; savings confidence; duration on ART; frequency discussing sensitive topics with caregivers; household size; economic group assignment; and school enrollment.

Conclusions: Our findings support potential use of ML methods and socio-behavioral data for predicting poor ART adherence risk among ALWHIV. The predictive tool can help identify ALWHIV at the highest risk of treatment failure, and enable early targeted interventions. However, the tool is still preliminary and its accuracy could be improved by incorporating HIV phenotypic and clinical data.

Clinical trial number: ClinicalTrials.gov ID:NCT01790373.

Objective: Men with HIV have more coronary atherosclerosis than men without HIV. We examined whether plaque progression differed based on HIV serostatus.

Design: We examined plaque progression over a median of 4.5 years (IQR 3.9-4.9) among 548 men with (n = 313) or without (n = 235) HIV from the Multicenter AIDS Cohort Study using coronary CT angiography.

Methods: Change in coronary plaque volume was calculated for 1) total, 2) calcified, 3) noncalcified, and 4) low attenuation plaque and categorized by tertile. Multinomial logistic regression models estimated the association between HIV and coronary plaque progression.

Results: The median age was 53 years old and 30% were Black. Total plaque volume regressed among 2%, 20% remained without plaque, and 78% had progression with a median progression of 34 mm3 (IQR 3-106). Compared to men without HIV, men with HIV had a statistically significant 1.99 higher odds of calcified plaque progression (95%CI:1.16,3.44, p = 0.01) and elevated odds for progression in total plaque (OR1.62, 95%CI:0.94,2.77, p = 0.08) and noncalcified plaque volume (OR1.64, 95%CI:0.97,2.79, p = 0.07), although the latter findings did not meet the cutpoint for statistical significance. The progression of low attenuation plaque did not significantly differ by HIV serostatus (OR1.34, 95%CI:0.88,2.05, p = 0.18). HIV was significantly associated with the progression of total, calcified, and noncalcified plaque among nonBlack participants, but not Black participants.

Conclusions: These results suggest that men with HIV may have greater plaque progression, which may contribute to the observed higher incidence of coronary heart disease among men with HIV.

Objective: We characterized sociodemographic and behavioural factors associated with mortality among people living with HIV (PLWH) in British Columbia (BC), Canada.

Design: We used purposive sampling to recruit a representative cohort of PLWH aged ≥19 years from January 2016-September 2018. Participants completed a survey and consented to link their data with the BC Vital Statistics Agency, where deaths were recorded.

Methods: We conducted bivariate analyses to compare characteristics between participants who died with those alive as of September 2021. We used multivariable Cox proportional hazards models to examine factors associated with mortality.

Results: As of September 2021, 71 (11.0%) of 644 participants died. The most common specified cause of death was due to overdose (n = 14, 19.7%). A higher proportion of individuals who died had been incarcerated (52.1% vs. 33.3%; p = 0.002), reported recent homelessness (28.2% vs. 12.6%; p < 0.001) and recent injection drug use (32.4% vs. 19.0%; p = 0.009), compared to those alive at the end of follow-up. Age ≥60 (adjusted hazard ratio [aHR] 3.80, 95% CI 1.55-9.34), and experiencing homelessness in the last 12 months prior to enrolment (aHR 2.01, 95% CI 1.18-3.61) were associated with an increased hazard of death, while identifying as gay or lesbian (aHR 0.42, 95% CI 0.23-0.77), and having greater social support (aHR 0.88 per 10-unit score increase, 95% CI 0.81-0.96) were protective.

Conclusions: Over six years of follow-up, more than 10% of our cohort died, with overdose being the most commonly reported cause of death. PLWH with higher social support however had a lower risk of death in BC.

Objective: Higher inflammation and lower neurodevelopmental outcomes (ND) have been reported in children exposed to HIV but uninfected (CHEU) compared to children unexposed to HIV (CHU) during infancy, but whether these differences persist in early childhood is unclear. We assessed pro- and anti-inflammatory biomarkers and their associations with ND in CHEU and CHU aged 18-36 months.

Design: Cross-sectional study of 45 CHEU and 36 CHU aged 18-36 months enrolled in Eldoret, Kenya.

Methods: Plasma levels of 65 cytokines, chemokines, growth factors, and soluble receptors, and 16 soluble immune checkpoints (ICPs) were quantified using multiplex immunoassays. Monocyte activation (sCD14, sCD163) and endothelial activation (CD146, ICAM-1, VCAM-1) plasma levels were measured by ELISAs. ND was assessed using the culturally adapted developmental assessment of cognition, language, and motor function. Predictors of ND were assessed using Bayesian Model Averaging of the linear regression model.

Results: CHEU exhibited lower levels of several chemokine and growth factors and four inflammatory cytokines compared to CHU: APRIL (p = 0.03), IL-12p70 (p < 0.001), MIF (p = 0.002), and Tweak (p = 0.003). Conversely, two soluble ICPs, CD40 (p = 0.02) and TIM3 (p = 0.001), were higher in CHEU compared to CHU. IL-22 and SDF-1α emerged as the strongest predictors of neurodevelopment in CHEU and CHU, respectively.

Conclusion: In early childhood, CHEU exhibited an immunosuppressive rather than inflammatory biomarker profile. Immune biomarkers more frequently predicted ND than social and demographic factors, and the predictors of cognitive, motor, and language outcomes differed between CHU and CHEU. Further research is necessary to explore the connection between childhood neurodevelopment and immune biomarkers.

Objective: People with HIV-HCV co-infection need antiretroviral treatment (ART) to suppress HIV and direct-acting antivirals (DAAs) to cure HCV. ART is typically prioritized, but delays in DAA initiation may increase the risk of liver-related events and HCV transmission to others.

Design: Target trial emulation with observational data collected in routine clinical practice from a collaboration of cohorts from Europe and North America.

Methods: We included DAA-naïve adults with HIV-HCV co-infection who achieved HIV virologic suppression (HIV RNA<50 copies/mL) after starting ART between 2013-2020. We 1) estimated the probability of not initiating DAAs at 6 and 36 months after HIV virologic suppression, and 2) emulated a target trial of early (≤6 months after HIV virological suppression) versus delayed (>6 months) DAA initiation and the 36-month risk of liver-related events (liver decompensation or hepatocellular carcinoma).

Results: Of 862 eligible individuals (median age 46 years; interquartile range 36 to 56), 14% were women, and 52% had a history of injection drug use. The 6 and 36-month probabilities of not initiating DAA were 58% (95% CI: 55, 61) and 24% (21, 27), respectively. The 36-month risk of liver-related events was 1.1% (0.4, 2.0) for early initiation and 1.7% (0.7, 2.5) for delayed initiation; risk difference -0.5% (-1.2, 0.4).

Conclusions: Almost one-quarter of people with HIV-HCV co-infection on ART had not initiated DAA 3 years after HIV virologic suppression. Because the 3-year risk of liver-related events was low, estimates of the impact of delayed DAA initiation were imprecise.

Objectives: To investigate the short- and long-term dynamics of intact and defective proviral HIV DNA during ART.

Design: We evaluated viral reservoir dynamics in a cohort of nine individuals with chronic HIV-1 subtype B infection who initiated first-line ART and were followed for 20 years while continuing ART.

Methods: PBMCs were obtained before ART (n = 5), during the first year, and after 8.5 and 20 years of treatment. T cell subsets (naive, central-memory, transitional-memory and effector-memory) were sorted at 8.5 and 20 years. DNA was isolated and analyzed using the intact proviral DNA assay (IPDA). Deep-sequencing of the viral env region enabled analysis of viral evolution and cellular mechanisms underlying HIV persistence.

Results: Initially, defective and intact proviral DNA in PBMCs declined with half-lives of 3.6 and 5.4 weeks, respectively. Over the following 8.5 years, the intact reservoir continued to decrease, with a half-life of 18.8 months in PBMCs, while defective proviral DNA levels stabilized. After 8.5 and 20 years of ART, the intact reservoir showed no further decline, with most intact proviral DNA residing in memory T cell subsets. Phylogenetic analysis revealed no signs of viral evolution over time, both within and between T cell subsets.

Conclusions: PBMCs containing intact proviral DNA are selectively lost during the first decade of suppressive ART, followed by a decade of stabilization of this reservoir in the memory T cell subsets. In the absence of clear signs of viral evolution and massive clonal expansion, homeostatic proliferation might be an important driver of HIV persistence during long-term ART.

Objective: After analytical treatment interruption (ATI), viral rebound occurs in most people with HIV. The time to viral rebound (TTVR) is likely determined by the properties of the viral reservoir as well as the anti-viral immune response. Soluble biomarkers of immune activation may be predictive of TTVR and plasma viral load (pVL) setpoint after ATI. The objective of this study is to identify these soluble biomarkers.

Design: A retrospective biomarker analysis of the Primo-SHM trial who were treated 24 or 60 weeks during early HIV infection.

Methods: Thirty-five biomarkers were measured at ATI in 65 participants. Association between biomarkers and reservoir size, TTVR and pVL at setpoint was assessed.

Results: SCD14 correlated to pVL setpoint (B = 0.598; p = 0.004) and lower levels of IL-12p70 to a higher level of pVL setpoint (B = -0.448; p = 0.04). SCD163 correlated to levels of total HIV-DNA (B = 0.413; p = 0.007).

Conclusions: An increased pVL setpoint was associated with higher sCD14 and lower IL12-p70 at ATI and increased total HIV-DNA was associated with higher sCD163 at ATI. SCD14 and sCD163 are biomarkers of monocyte activation, while IL12-p70, produced by monocytes, is essential for inducing Th1 responses. This underscores the relation between immune activation and diminished immune control of HIV. Our findings indicate that sCD14 and IL-12p70 could serve as predictive biomarkers for favorable outcomes in cure interventions.

Objective: Social networks may play a vital role in shaping health behaviors, including engagement in HIV prevention and treatment. We evaluated the impact of an HIV status-neutral, social-network-based HIV self-testing and linkage intervention on pre-exposure prophylaxis (PrEP) adherence and HIV viral suppression among men working alongside Lake Victoria, Kenya.

Design: Cluster-randomized controlled trial.

Methods: After a census of fishermen, distinct social networks with highly socially-connected men were identified, "promoters" per network were recruited, and networks were randomized to study arms. Promoters distributed HIV self-tests kits to fishermen in their network and encouraged linkage and retention in prevention and care (intervention) or distributed vouchers redeemable for routine HIV testing (control). We report the tertiary outcomes of a) PrEP adherence, measured via a urine tenofovir assay among PrEP users, and b) viral load among PLHIV. We conducted a logistic regression to evaluate the intervention's association with PrEP adherence and viral suppression.

Results: Of 733 baselined, 339 linked to clinics: 62 initiated PrEP, 25 were already on PrEP, and 166 were living with HIV. Urine tenofovir was detected among 12 of 70 participants who gave urine samples (14% control vs. 19% intervention), and 43 of 166 participants on antiretroviral therapy had detectable viral loads (40.2% control vs. 35.7% intervention). There were no significant differences by arm in urine tenofovir levels nor viral suppression.

Conclusions: A social network-based, status-neutral intervention that increased men's testing and linkage was not associated with PrEP adherence nor viral suppression. An adequately-powered study is necessary to evaluate whether social-network-based interventions can improve these outcomes.

Objective: Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma (NHL) subtype caused by Kaposi sarcoma (KS) herpesvirus. We describe PEL incidence and survival in people with HIV (PWH) and people without HIV in the US.

Design: Retrospective cohort study of PEL people with and without HIV.

Methods: PEL cases were identified in the HIV/AIDS Cancer Match (HACM) Study, a linkage of population-based cancer and HIV registries in 14 US regions. PEL incidence was examined using negative binomial regression and compared with the general population using a standardized incidence ratio. Survival was evaluated using Cox proportional hazard regression.

Results: During 2001-2019, 53% of 174 PEL cases identified in HACM data were among PWH. PWH had >700-fold higher PEL incidence than the general population. Compared to PEL cases without HIV, PWH were younger (median age: 44.8 vs. 77.7 years). Among PWH, prior KS was associated with 59-fold higher PEL incidence versus those without an AIDS diagnosis. PEL comprised 1.15% of the 8010 NHLs diagnosed among PWH in HACM during 2001-2019. HIV was not associated with mortality among PEL cases. Among PWH, Burkitt lymphoma and diffuse large B-cell lymphoma exhibited similar mortality to PEL but central nervous system lymphoma mortality was worse.

Conclusions: There are two distinct subgroups of PEL cases in the US: younger patients with HIV and older patients without HIV. The proportion of PEL cases among PWH is highly disproportionate to the size of the HIV population, reflecting the greatly elevated incidence of PEL among PWH.

Objectives: We evaluated antiviral effectiveness and safety of doravirine (DOR)-based regimens in people with HIV (PWH) in routine clinical practice.

Design: A retrospective, noninterventional study across 16 sites in five European countries [United Kingdom (UK), France, Spain, Belgium, Netherlands].

Methods: The study was conducted in both treatment-experienced and treatment-naive PWH who either switched to, or initiated DOR-containing antiretroviral therapy (ART). The primary endpoints were virological success (defined as the percentage of participants with HIV RNA <50 copies/ml, using FDA Snapshot method) and virological failure (FDA Snapshot, HIV RNA ≥50 copies/ml) at 48 weeks after initiation of DOR regimen.

Results: Between August 2017 and February 2022, 394 participants were enrolled, 63 naive and 331 treatment-experienced. 75.4% were men, with a median age of 45 years, and 92.2% received DOR in combination with tenofovir disoproxil fumarate and lamivudine or emtricitabine. The proportion of participants with virological success at week 48 after initiation of DOR regimen was 90.6% [95% confidence interval (CI) 87.3-93.3] overall, 87.3% (95% CI 76.5-94.4) in the ART-naive group, and 91.2% (95% CI 87.7-94.1) in the switch group. The proportion of participants with virological failure was 3.3% (95% CI 1.8-5.6) overall, 1.6% (95% CI 0-8.5) in the ART-naive group and 3.6% (95% CI 1.9-6.2) in the switch group. Of the 394 included participants, two (0.5%) were lost to follow-up and 13 (3.3%) discontinued the DOR regimen, four (1%) due to adverse events.

Conclusion: Our results show high levels of efficacy and low levels of side effects in DOR-containing regimens in both treatment-naive and treatment-experienced PWH.