AIDS最新文献

Objective: To study the subcutaneous adipose tissue (SAT) transcriptome in people with HIV (PWH) switching efavirenz (EFV) or a protease inhibitor (PI) to raltegravir and to compare the transcriptome of PWH to those of people without HIV (PWoH).

Design: PWH (n = 36) on EFV (n = 22) or a PI (n = 14) based ART regimen were randomized to switch to RAL (n = 15) or to continue unchanged medication (n = 17). PWoH (n = 10), comparable in age and body mass index, were included for comparison.

Methods: SAT gene expression was analyzed via RNA sequencing (Illumina Stranded mRNA library prep).

Results: At baseline, only 51 out of 19930 genes showed differential expression (FDR <0.05) between PWH and PWoH. Differentially expressed genes in PWH were identified as being HIV host factors or were associated with immune response, lipid metabolism, adipogenesis, apoptosis regulation, DNA/RNA metabolism, and cell structures. Mitochondria-encoded genes were consistently downregulated in PWH. Intergroup variations among PWH using different ART (EFV, PI, RAL) were not significant, and switching EFV or a PI to RAL did not induce substantial changes in the SAT transcriptome.

Conclusions: While some specific genes linked to HIV are differentially expressed in PWH compared to PWoH, the overall SAT transcriptome remains relatively stable across various antiretroviral treatments and upon switching from EFV/PI to RAL. These findings enhance our understanding of the molecular landscape on SAT in the context of HIV and ART.

Objective: To compare arterial stiffness between young adults with perinatally acquired HIV (YAPHIV) and young adults perinatally HIV exposed but uninfected (YAPHEU).

Design: Cross-sectional analysis of pulse wave velocity (PWV) measures among participants with echocardiography in the PHACS Cardiac Toxicity Substudy.

Methods: A total of 150 participants (95 YAPHIV, 55 YAPHEU, mean 23.4 years, 60% female, 72% Black, 24% Hispanic) had echocardiography and PWV measured. We compared PWV between groups. Among YAPHIV, we fit linear regression models to evaluate the association of measures of HIV disease severity and antiretroviral treatment (ART) with PWV. We computed correlations between PWV and measures of left ventricular structure and function.

Results: Mean PWV did not differ by group (YAPHIV 5.63 vs YAPHEU 5.39 m/s; P = 0.50). HIV control was good (82% with viral load <400 copies/ml); 91% used combination ART. Mean PWV was normal, but 3 of 95 YAPHIV (3%) had values above 11.8 m/s (level associated with cardiovascular events in adults). Weak correlations (<0.20) were observed between PWV and echocardiographic measures. Among YAPHIV, current and historical HIV severity measures were not associated with PWV. YAPHIV on protease inhibitor (PI)-based ART had higher mean PWV than those on integrase strand inhibitors (1.68 m/s higher, 95% CI -0.36, 3.72) or nonnucleoside transcriptase inhibitors (1.58 m/s higher, 95% CI -0.94, 4.11).

Conclusions: Our data shows no difference in PWV between those perinatally exposed to and perinatally infected with HIV. Therefore, CV risk reduction guidelines should be followed to prevent CV disease in all young adults.

Objectives: To predict the burden of HIV in the United States (US) nationally and by region, transmission type, and race/ethnicity through 2030.

Methods: Using publicly available data from the CDC NCHHSTP AtlasPlus dashboard, we generated 11-year prospective forecasts of incident HIV diagnoses nationally and by region (South, non-South), race/ethnicity (White, Hispanic/Latino, Black/African American), and transmission type (Injection-Drug Use, Male-to-Male Sexual Contact (MMSC), and Heterosexual Contact (HSC)). We employed weighted (W) and unweighted (UW) n-sub-epidemic ensemble models, calibrated using 12 years of historical data (2008-2019), and forecasted trends for 2020-2030. We compared results to identify persistent, concerning trends across models.

Results: We projected substantial decreases in incident HIV diagnoses nationally (W: 27.9%, UW: 21.9%), and in the South (W:18.0%, UW: 9.2%) and non-South (W: 21.2%, UW: 19.5%) from 2019 to 2030. However, concerning nondecreasing trends were observed nationally in key sub-populations during this period: Hispanic/Latino persons (W: 1.4%, UW: 2.6%), Hispanic/Latino MMSC (W: 9.0%, UW: 9.9%), people who inject drugs (PWID) (W: 25.6%, UW: 9.2%), and White PWID (W: 3.5%, UW: 44.9%). The rising trends among Hispanic/Latino MMSC and overall PWID were consistent across the South and non-South regions.

Conclusions: Although the forecasted national-level decrease in the number of incident HIV diagnoses is encouraging, the US is unlikely to achieve the Ending the HIV Epidemic in the US goal of a 90% reduction in HIV incidence by 2030. Additionally, the observed increases among specific subpopulations highlight the importance of a targeted and equitable approach to effectively combat HIV in the US.

Objective: This study evaluates changes in HIV transmission and the effectiveness of interventions after two rounds of the Guangxi AIDS Conquering Project (GACP) in Guangxi, China.

Methods: Samples and epidemiological data from newly diagnosed people living with HIV (PLWH) between 2014-2020 were analyzed. Molecular networks were constructed using nested PCR amplification and sequencing of the pol region, and multivariable logistic regression identified factors associated with clustering and high-degree nodes.

Results: A total of 4,227 valid sequences (73.12% inclusion rate) were analyzed. Demographic changes included an increasing proportion of individuals aged ≥50 years (49.66%), with lower education (50.51%), peasants (76.82%), and heterosexual transmission (90.29%). The overall clustering rate was 86.89%, with higher clustering among individuals aged ≥50 (92.57%), those with primary school or below (89.09%), peasants (88.11%), and CRF08_BC infections (91.48%). Annual declines in cluster growth rate and clustering rates were observed, particularly among individuals aged <30, college graduates, men who have sex with men (MSM), and people who inject drugs (PWID). Key transmission hotspots were identified in Lingshan, particularly among older, less-educated individuals, and peasants. Factors associated with clustering included being male (aOR: 1.27), aged ≥50 (aOR: 3.84), and infected with CRF08_BC (aOR: 2.12). From 2017 to 2020, the risk of clustering and high-degree nodes was lower compared to 2014-2016, suggesting the effectiveness of interventions.

Conclusion: Interventions in Guangxi effectively reduced HIV transmission among younger, high-degree populations. However, older, less-educated individuals remain at high risk, necessitating targeted strategies to address their specific needs and achieve better HIV control.

Objective: We aimed to identify preferences for PrEP care among diverse gay, bisexual, and other men who have sex with men (BLGBM) in the US with discrete choice experiment (DCE).

Design: We conducted two DCEs to elicit care delivery preferences for Starting and Continuing PrEP among 16-49 year-old HIV negative GBM not using PrEP from across the United States. DCEs assessed preferences for care options including location, formulation (pills, injectable), lab testing, and costs. Participants completed 16 choice tasks and utility scores and relative importance were estimated. We performed latent class analyses to identify groups within each DCE, and multivariable logistic regression to identify sociodemographic characteristics associated with class membership.

Results: Among 1514 participants, 46.5% identified as Latino, 21.4% Black, and 25.2 White. For Starting PrEP DCE, two latent classes were identified: "In-Person" (28.5%) which preferred in-person care and lab testing, and "Virtual" (71.5%) which preferred telehealth and at-home lab testing. For Continuing PrEP DCE, two latent classes were identified: "Pills" (23.6%) which preferred oral PrEP with low-cost options and "No Cost/Injectable" (76.4%) which strongly preferred no-costs and injectable PrEP. In multivariable models for Starting PrEP and for Continuing PrEP, latent class membership was significantly associated with a range of sociodemographic characteristics including race/ethnicity, income, housing instability, and provider and PrEP stigma.

Conclusions: The preferences identified for PrEP care in this diverse GBM sample indicate the need for multiple care and formulation choices including elimination of costs to improve PrEP uptake. DCE findings can guide implementation efforts to improve equitable access to PrEP.

Objective: To discover microRNA (miRNA)-RNA transcript interactions dysregulated in brains from persons with HIV-associated neurocognitive disorder (HAND), we investigated RNA expression using machine learning tools.

Design: Brain-derived host RNA transcript and miRNA expression was examined from persons with or without HAND using bioinformatics platforms.

Methods: By combining next generation sequencing, droplet digital (dd)PCR quantitation of HIV-1 genomes, with bioinformatics and statistical tools, we investigated differential RNA expression in frontal cortex from persons without HIV (HIV[-]), with HIV without brain disease (HIV[+]), with HIV-associated neurocognitive disorder (HAND), or HAND with encephalitis (HIVE).

Results: Expression levels for 147 transcripts and 43 miRNAs showed a minimum 4-fold difference between clinical groups with a predominance of antiviral (Type I interferon) signaling-, neural cell maintenance-, and neurodevelopmental disorder-related genes that was validated by gene ontology and molecular pathway inferences. Scale of signal-to-noise ratio (SSNR) and biweight midcorrelation (bicor) analyses identified 14 miRNAs and 45 RNA transcripts, which were highly correlated and differentially expressed (p ≤ 0.05). Machine learning applications compared regression models predicated on HIV-1 DNA, or RNA viral quantities that disclosed miR-4683 and miR-154-5p were dominant variables associated with differential expression of host RNAs. These miRNAs were also associated with antiviral-, cell maintenance-, and neurodevelopmental disorder-related genes.

Conclusions: Antiviral as well as neurodevelopmental disorder-related pathways in brain were associated with HAND, based on correlated RNA transcripts and miRNAs. Integrated molecular methods with machine learning offer insights into disease mechanisms, underpinning brain-related biotypes among persons with HIV that could direct clinical care.

Objective: To evaluate the impact of ART duration and CD4 count on risk for high grade cervical dysplasia in women with HIV (WWH) compared to women without HIV in the treat-all era with integrase strand inhibitors (INSTIs).

Design: Prospective longitudinal cohort study in Botswana.

Methods: From February 2021 to August 2022, baseline HPV self-sampling was offered to women with and without HIV. Those HPV+ underwent biopsy for histopathological diagnosis. Using women without HIV as reference, risk ratios (RRs) were calculated for HPV, cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), and CIN3+, stratified by ART duration and CD4 cell counts.

Results: Of 3000 women enrolled, 2953(98.4%) underwent HPV testing, which was positive in 823(55.7%) WWH and in 654(44.3%) women without HIV. Histopathology was available for analysis in 1291(87.4%) women (709 WWH, 582 women without HIV). Over 99% of WWH had detectable HIV viral load and 94.4% were on a dolutegravir-based ART regimen. WWH had a higher risk of HPV (RR1.27,95%CI:1.18,1.37), CIN2+ (RR1.52,95%CI:1.16,1.98) and CIN3+ (RR1.75,95%CI:1.25,2.45) compared to women without HIV. There was attenuation of risk for CIN2+ with higher recent CD4 cell count, and those with higher nadir CD4 count had similar risk to those without HIV (nadir CD4≥500 CIN2+ RR1.15[95%CI:0.56,2.37], CIN3+ RR1.81[95% CI:0.86,3.79]; nadir CD4 350-499 CIN2+ RR1.23[95% CI:0.71,2.12], CIN3+ RR1.34[95%CI:0.68,2.64]).

Conclusion: Although some attenuation of risk for CIN2+ was observed with higher recent and nadir CD4 cell counts, WWH continue to have a higher risk of CIN2+/CIN3+ compared to women without HIV. These findings support tailored cervical screening algorithms for WWH.

Objective: Most data published on adolescents living with HIV (ALH) have been collected before the large diffusion of second-generation integrase strand transfer inhibitors (INSTI) among the pediatric population. We analyzed the nationwide ANRS-MIE CO10 Pediatric cohort to assess the changes over time in health and social outcomes of French ALH.

Design: The cohort enrolled children born in France since 1985 and, from 2005, children diagnosed with HIV at ≤13 years, including those born abroad if antiretroviral-naive at first medical care in France.

Methods: Adolescents aged ≥10 years at their last visit were included in this analysis. Their characteristics were compared between three periods of birth (1985-1993, 1994-1999, 2000-2010).

Results: Overall, 529 ALH were included. Their median age at first HAART initiation decreased from 94 to 29 months (p < 0·0001). At the last evaluation, the proportions of ALH receiving HAART, receiving INSTI, having HIV-RNA < 50 copies/mL and having CD4 count ≥500/μL increased over time (p < 0.0001), reaching 98·7%, 53·3%, 81·3% and 85·0%, respectively, for those born in 2000-2010. The proportion of maternal and paternal orphans decreased until 14·4% and 11·0%, respectively, for ALH born recently. Compared to middle adolescents (15-17 years) born in 1994-1999, those born in 2000-2010 demonstrated higher academic success (69·2% versus 42·3%) and less frequent academic failure (4·6% versus 6·2%).

Conclusions: Despite spectacular improvement in their health and immunovirological status, ALH remain vulnerable compared to other French adolescents, with a higher risk of being orphan and/or experiencing academic failure. Specific interventions are required to improve their global quality of life.

Introduction: In France, over 90% of people living with HIV-1 (PLWH) achieve virological suppression with effective combination of antiretroviral therapies (ART), but limited data exist on the motivation for switching ART.

Objective: To describe the reasons and determinants for switching ART, with a particular focus on doravirine-based regimens, in routine clinical practice in France.

Design: This analysis of cross-sectional baseline data is part of the DoraVIH study, a French, multicenter (15 sites), two-step observational cohort study that includes prospective follow-up for a subset of participants.

Methods: Eligible participants were PLWH under ART regimen, virologically suppressed for at least 6-months, doravirine-naïve and switching ART regimen. Sociodemographic and clinical data, ART history, and reasons for switching ART were assessed at baseline.

Results: Inclusions occurred between December 13, 2021 and September 21, 2022. Of the 291 PLWH included whose data were analyzed, 143 switched to doravirine-based regimen (DOR PLWH) and 148 to another combined regimen (non-DOR PLWH). Mean age was 51.6 years and 206 participants (70.8%) were men. At baseline, 35 (25.0%) DOR PLWH and 15 (10.6%) non-DOR PLWH had Body Mass Index (BMI) ≥30 kg/m 2 (p = 0.007). The most common reasons for switching were treatment simplification, tolerability and drug-drug interactions, accounting for 79.7% of all reasons. Among the 68 participants with prior tolerability issues, 47 (69.1%) switched to doravirine-based regimen.

Conclusions: Primary reasons for switch were treatment simplification and tolerability. Participants with obesity were more likely to switch to doravirine, reflecting physicians' favorable perception of doravirine potential benefits, particularly in managing weight gain.

Background: Objectives were to determine the prevalence/incidence of HPV-related dysplasia and clearance/acquisition rates of high-risk HPV (HR-HPV) genotypes in genital mucosa of women-LHIV and oropharyngeal and anal mucosa of PLHIV and to evaluate factors related to HR-HPV infection in oropharyngeal mucosa at 12-months.

Material and methods: Prospective, longitudinal study with 12-month follow-up, enrolled PLHIV between December 2022 and April 2023. At baseline and 12-months, HIV-related clinical and analytical variables were recorded, oropharyngeal mucosa exudates were taken for polymerase chain reaction (PCR) studies for HPV and other sexually transmitted infections, while anal and female genital samples were self-sampled for HPV detection and genotyping by PCR and thin-layer cytology.

Results: 276 PLHIV with mean age of 45.3 years, 79% male, 24.3% with history of AIDS, 100% under ART, and 30.1% with completed HPV vaccination. HPV infection prevalence in oropharyngeal mucosa was 11.6% at baseline, most frequently by genotype 16 (2.2%), without dysplasia. No oropharyngeal dysplasia was observed at 12 months, and HR-HPV clearance and acquisition rates were 5.5% and 4.4%, respectively. Incidence of anal HSIL was 1,811.6 casesx100,000 people-year, and HR-HPV clearance and acquisition rates were 16.2% and 25.6%, respectively. Incidence of CIN2/CIN3 or cervical cancer was zero, and HR-HPV clearance and acquisition rates were 11.3% and 7.5%. HIV-RNA viral load <50 cop/mL protected against HPV infection in oropharyngeal mucosa (97.2 vs. 87%, HR 0.044; 95%CI [0.042 - 0.956]).

Conclusions: Among PLHIV, HSIL incidence and HR-HPV acquisition rate are higher in anal versus oropharyngeal and genital mucosae. Non-detectability protects against oropharyngeal HPV infection.