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Background: Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related central nervous system (CNS) co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on neurocognitive functioning in PWH with TE compared to LTI or no toxoplasmal infection.

Methods: PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti- toxoplamic immunoglobulin G (IgG) assay. Participants were classified into one of three groups: TE+ ( n  = 39), LTI+ ( n  = 34), LTI- ( n  = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit.

Results: The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/ml) and had lower absolute CD4 + cell count. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants.

Conclusions: PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

Objective: The ability of HIV-1 Nef to counteract the host restriction factor SERINC5 and enhance virion infectivity has been well-established. However, the impact of long term within-host Nef evolution on this antagonistic capability remains unclear.

Design: Analysis of longitudinal activity of Nef in antagonizing SERINC5.

Methods: We investigated the downregulation activity of Nef against SERINC5 at different stages of infection by analyzing the cognate transmitted/founder, set point, and/or chronic Nef isolates from a cohort of 19 subjects living with either subtype B or C HIV-1.

Results: The Nef isolates from different stages exhibited varying abilities to antagonize SERINC5. Long-term evolution resulted in mutations accumulated in Nef and a decline of Nef-mediated SERINC5 downregulation function in subtype B, but not in subtype C viruses, leading to a rapid reduction in viral load from peak viremia. Furthermore, we identified four polymorphisms of both subtype B and C Nef that are associated with variations in the SERINC5 antagonistic function and viral infectivity. HIV-1 NL4-3 variants encoding Nef E63G, A83G, R105K, or D108E mutants exhibited reduced replication capacity through a SERINC5-dependent mechanism. However, among different subjects, only a small part of naturally occurring mutations at these sites were selected by host T cell responses, suggesting a limited impact of host T cell responses on influencing Nef's ability to antagonize SERINC5.

Conclusion: These results highlight the potential contribution of functional variation in Nef to differences in HIV-1 pathogenesis and provide significant implications for understanding the evolutionary interaction between Nef and SERINC5 in vivo .

Objective: Using an innovative data sharing model, we assessed the impacts of the COVID-19 pandemic on the health of people who inject drugs (PWID).

Design: The PWID Data Collaborative was established in 2021 to promote data sharing across PWID studies in North America. Contributing studies submitted aggregate data on 23 standardized indicators during four time periods: pre-pandemic (Mar 2019 - Feb 2020), early-pandemic (Mar 2020 - Feb 2021), mid-pandemic (Mar 2021 - Feb 2022), and late pandemic (Mar 2022 - Feb 2023).

Methods: We present study-specific and meta-analyzed estimates for the percentage of PWID who took medications for opioid use disorder, received substance use treatment, shared syringes or injection equipment, had a mental health condition, had been incarcerated, or had experienced houselessness. To examine change over time across indicators, we fit a random effects meta-regression model to prevalence estimates using time as a moderator.

Results: Thirteen studies contributed estimates to the Data Collaborative on these indicators, representing 6,213 PWID interviews. We observed minimal change across prevalence of the six indicators between the pre-pandemic (March 2019 - February 2020) and three subsequent time periods, overall or within individual studies. Considerable heterogeneity was observed across study- and time-specific estimates.

Conclusions: Limited pandemic-related change observed in indicators of PWID health is likely a result of policy and supportive service-related changes and may also reflect resilience among service providers and PWID themselves. The Data Collaborative is an unprecedented data sharing model with potential to greatly improve the quality and timeliness of data on the health of PWID.

Objectives: Substance use disorders (SUDs) are a significant public health concern across the United States and may pose a risk to achieving sustained viral suppression (SVS) in people with HIV (PWH). This study aims to examine the association between SUDs and SVS among PWH.

Design: Using electronic health records from the South Carolina Department of Health, we conducted a retrospective study of adults diagnosed with HIV between January 2006 and December 2019.

Methods: The impact of SUDs on SVS was assessed using generalized linear mixed model. Potential confounders included age, sex, chronic diseases history, etc. Stepwise selection was performed to decide the confounders included in the final model, and the optimal correlation structure was determined by Akaike information criterion.

Results: Of the 9412 eligible participants, 7481 (79.48%) had reached SVS status during their follow-up periods. SUDs related to alcohol (adjusted odds ratio (AOR) = 1.70, 95% confidence interval (CI): 1.46-1.98), cannabis (AOR = 1.62, 95% CI: 1.35-1.95), cocaine (AOR = 1.95, 95% CI: 1.60-2.37), opioid (AOR = 1.91, 95% CI: 1.13-3.23), and tobacco (AOR = 1.80, 95% CI: 1.69-1.92) were negatively associated with SVS. Individuals with chronic conditions such as cardiovascular disease (AOR=0.31, 95% CI: 0.29-0.33), diabetes (AOR=0.49, 95% CI: 0.41-0.59), and cancer (AOR=0.47, 95% CI: 0.38-0.58) showed a higher likelihood of maintaining SVS.

Conclusion: This large cohort study of PWH with extended follow-up highlights the negative impact of SUDs on maintaining SVS. Long-term strategies for reducing substance use could support SVS in HIV patients.

Objective: To characterize the immune functionality and phenotype and the proviral composition of a cohort of young adults with perinatally-acquired HIV (p-YA) from Argentina.

Design: Cross-sectional study of 18 p-YA, 15 young adults with non-perinatally acquired HIV matched by age with p-YA and 14 adults with non-perinatally acquired HIV, matched by time from HIV diagnosis with p-YA, all from Argentina.

Methods: Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on NK and T-cells. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4 T-cells by IPDA. Soluble markers were determined by ELISA.

Results: p-YA displayed lower expression of PD-1, higher levels of CD38+ CD4 T-cells and increased levels of naïve T-cells than control groups. Also, a trend of lower levels of IP HIV-DNA normalized to CD4 T-cell counts and to the proportion of naïve T-cells was found in p-YA.

Conclusion: The higher frequency of naïve CD4 T-cells in p-YA cannot be explained by elevated thymic activity nor by a higher T-cell proliferation rate. This imbalance could have been generated early in life and persisted during adulthood. Naïve CD4 T-cells may not serve as a major viral reservoir in p-YA. Also, the lower PD-1+ CD4 T-cell count suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for proviral eradication.

Background: We aimed to provide insights into the effects of comorbidities on sleep health in people with HIV by assessing associations between multimorbidity patterns and sleep outcomes in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) sub-study.

Methods: Principal component analysis identified six multimorbidity patterns among participants with HIV (n = 1073) at baseline: Cardiovascular diseases (CVDs), Sexually transmitted diseases, Metabolic, Mental/Joint, Neurological and Cancer/Other. Burden z-scores were calculated for each individual/pattern. A subset of 478 participants completed sleep assessments at follow-up, including questionnaires (Insomnia Severity Index [ISI], Patient-Reported Outcomes Measurement Information System [PROMIS] Sleep Disturbance [SD] and Sleep Related Impairment [SRI]) and overnight oximetry (4% oxygen desaturation index [ODI] and percentage of time with oxygen saturation [SpO2] <90%). Multivariable regression assessed associations between burden z-scores and sleep measures.

Results: Amongst 309 participants (median [interquartile range] age 53 [47-59] years), 21% had insomnia (ISI≥15). Higher Mental/Joint z-scores were associated with increased odds of insomnia (aOR 1.06 [95%CI 1.03, 1.09]) and worse PROMIS-SRI (1.34 [1.22, 1.48]) and PROMIS-SD (1.27 [1.16, 1.39]) scores. Higher Metabolic and Neurological z-scores were associated with worse PROMIS-SRI scores (p < 0.01). Higher CVDs z-scores were associated with worse ISI and PROMIS-SRI scores, and a higher percentage of time with Sp02 below 90% (all p's < 0.01).

Conclusion: This study is among the first to describe specific multimorbidity patterns linked to poorer sleep outcomes in people with HIV. Findings suggest the need for targeted sleep interventions based on multimorbidity profiles, which may mitigate broader health risks associated with poor sleep.

Objective: To estimate the effect of antidepressant initiation on viral non-suppression among people with HIV (PWH) with clinically recognized, untreated depression.

Design: Retrospective, observational cohort study.

Methods: We included clinical diagnoses of depression from January 2012-June 2022 among PWH in the Johns Hopkins HIV Clinical Cohort without another serious psychiatric illness who had initiated antiretroviral therapy. We excluded diagnoses less than 90 days from a prior diagnosis, antidepressant prescription, or >1 mental health visits. We estimated the association between initiating an antidepressant within 1 month of the index depression diagnosis and viral load non-suppression (>200 copies/mL) on the first viral load 3-12 months subsequent. We adjusted for a comprehensive set of demographic and clinical confounders.

Results: We included 2,346 depression diagnoses among 946 patients; patients initiated an antidepressant following 16%. The risk of viral non-suppression in the absence of antidepressant treatment was 15.6% (95% confidence interval [CI]: 13.1, 18.4). Antidepressant initiation was not associated with viral non-suppression (risk difference: 0.5%; 95% CI: -3.7, 4.8) or secondary outcomes: improvement or resolution of depressive symptoms or adherence to scheduled clinic visits.

Conclusions: In this sample of patients with as-yet-untreated depression, in a setting with co-located, low-barrier psychiatric services, antidepressant treatment was not associated with improved viral suppression. Pharmacologic management of depression has documented benefits in other studies. However, there may be a subset of PWH with depression who have been previously unsuccessfully treated with antidepressants who are less likely to respond to approved pharmacologic options and who require different interventions to improve their viral suppression.