AIDS最新文献

Background: People with HIV (PWH) are at an increased risk of tuberculosis (TB). New TB vaccines may help reduce this burden. New TB vaccine candidates are well tolerated and immunogenic in PWH. There are currently limited data on vaccine efficacy in this population.

Methods: Using mathematical modeling, we explored the potential impact of a novel TB vaccine on TB burden in PWH in South Africa between 2030 and 2050. We compared the impact of a vaccine delivered irrespective of HIV status to vaccination of either PWH or people without HIV. We explored the impact of reduced vaccine efficacy and duration of protection in PWH relative to people without HIV on our model predictions.

Results: Vaccination irrespective of HIV status, with a vaccine with equal efficacy and duration in PWH, could avert up to 1.01 (95% range: 0.96-1.22) million TB cases in PWH. Restricting vaccination to PWH or people without HIV would achieve 65% (60-70) and 48% (46-53) of the total impact, respectively. These results are strongly dependent on the assumed efficacy and duration of protection in PWH. Further information on these characteristics is important to identify the most efficient use of new vaccines to reduce TB burden in PWH.

Conclusion: Our results suggest that new vaccines could play an important role in reducing the TB burden in PWH. Vaccines targeted at people without HIV could provide significant indirect benefit to PWH, but vaccines which are well tolerated and effective in PWH will be critical to maximizing the impact in this population.

Objective: Women with HIV (WHIV) are at an increased risk of adverse perinatal outcomes compared to women without HIV, despite antiretroviral therapy (ART). There is evidence that the risk of adverse perinatal outcomes may differ according to ART regimen. We aimed to assess the risk of adverse perinatal outcomes among WHIV receiving different classes of ART, compared to women without HIV.

Design: A systematic review and meta-analysis.

Methods: We searched Medline, CINAHL, Global Health, and EMBASE for studies published between January 1, 1980, and July 14, 2023. We included studies which assessed the risk of 11 predefined adverse perinatal outcomes among WHIV receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, protease inhibitor based ART or integrase strand transfer inhibitor (INSTI)-based ART, compared to women without HIV. The perinatal outcomes assessed were preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Random effects meta-analyses examined the risk of each adverse outcome in WHIV receiving NNRTI-based, protease inhibitor based, or INSTI-based ART, compared with women without HIV. Subgroup and sensitivity analyses were conducted based on country income status, study quality, and timing of ART initiation. The protocol is registered with PROSPERO, CRD42021248987.

Results: Of 108 720 identified citations, 22 cohort studies including 191 857 women were eligible for analysis. We found that WHIV receiving NNRTI-based ART (mainly efavirenz or nevirapine) are at an increased risk of PTB (risk ratio 1.40, 95% confidence interval 1.27-1.56), VPTB (1.94, 1.25-3.01), LBW (1.63, 1.30-2.04), SGA (1.53, 1.17-1.99), and VSGA (1.48, 1.16-1.87), compared with women without HIV. WHIV receiving protease inhibitor based ART (mainly lopinavir/ritonavir or unspecified) are at an increased risk of PTB (1.88, 1.55-2.28), VPTB (2.06, 1.01-4.18), sPTB (16.96, 1.01-284.08), LBW (2.90, 2.41-3.50), VLBW (4.35, 2.67-7.09), and VSGA (2.37, 1.84-3.05), compared with women without HIV. WHIV receiving INSTI-based ART (mainly dolutegravir) are at an increased risk of PTB (1.17, 1.06-1.30) and SGA (1.20, 1.08-1.33), compared with women without HIV.

Conclusion: The risks of adverse perinatal outcomes are higher among WHIV receiving ART compared with women without HIV, irrespective of the class of ART drugs. This underlines the need to further optimize ART in pregnancy and improve perinatal outcomes of WHIV.

Objectives: Virally suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used PET to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Design: Cross-sectional investigation in VS-PWH ( n  = 25) versus HIV-uninfected individuals ( n  = 18) of cognitive control and declarative memory, as well as [ 11 C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest (ROI).

Methods: Group differences in [ 11 C]DPA-713 binding ( VT ) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype.

Results: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [ 11 C]DPA-713 VT across cognitive control regions [unstandardized beta coefficient reflecting mean difference [ B ] = 0.23, SE = 0.11, 95% confidence interval (CI) 0.01-0.45, P  = 0.04] and declarative memory regions ( B   =  0.24, SE = 0.11, 95% CI 0.02-0.45, P  = 0.03). Higher log [ 11 C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [ 11 C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory.

Conclusion: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.

Background: Injectable depot medroxyprogesterone acetate (DMPA) is the most common contraceptive choice among young women in Uganda, where HIV burden is high and HIV preexposure prophylaxis (PrEP) may be offered. For young women who choose to use both agents concurrently, it is unknown whether they will experience declines in bone mineral density (BMD) beyond those elicited by either product singly.

Methods: From 2018 to 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 percent 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 to -1.56%, P  = 0.001), total hip -2.24% (95% CI -3.87 to -0.60%, P  = 0.009), and femoral neck -1.71% (95% CI -3.73 to 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.

Objectives: Worldwide, adult men experience an excess burden of tuberculosis (TB) disease compared with women, but few studies have examined sex differences in TB among people with HIV. In this study, we aimed to investigate sex differences in TB infection and disease among people with HIV in Rio de Janeiro, Brazil.

Design: Analysis of data from a randomized controlled trial and retrospective cohort study.

Methods: We analyzed data from two studies conducted between 2005 and 2017. The THRio Study (2005-2012) evaluated increasing tuberculin skin testing (TST) and TB preventive therapy (TPT), and Universal ART in Rio study (UnivART; 2010-2017) was a virtual cohort study of people with HIV and TB with data from four national electronic registries.

Results: Among 4606 people with HIV in THRio, 2992 (65.0%) had a TST placed and read, of whom 312 of 1865 (17%) males and 203 of 1127 (18%) females ( P  = 0.37) had prevalent TB infection. TB disease incidence was higher among males compared with females overall [IRR 1.33, 95% confidence interval (95% CI) 1.04-1.69], among males compared with females who did not receive TPT [incidence rate ratios (IRR) 1.30, 95% CI 1.01-1.67], and among males compared with females on ART (IRR 1.64, 95% CI 1.17-2.29). Among 54 957 people with HIV in UnivART, TB disease incidence rates were higher among males than females overall (IRR 1.28, 95% CI 1.18-1.39), among males compared with females on ART (IRR 1.58, 95% CI 1.40-1.77), and among males compared with females not on ART (IRR 1.11, 95% CI 0.99-1.25).

Conclusion: In this medium TB and HIV burden setting, TB disease incidence was higher among males than females with HIV, despite similar prevalence of TB infection.

Introduction: Alzheimer's disease and related dementias (AD/ADRD) continue to be a public health challenge. People living with HIV (PLWH) are at risk for neurocognitive disorders and may be at risk for AD/ADRD. However, studies examining clinical and sociodemographic factors associated with AD/ADRD among PLWH are lacking. Therefore, the aim of this cross-sectional study was to determine the association between selected sociodemographic (age, gender, race and rurality) and clinical (depression and encephalopathy) factors with (AD/ADRD) among PLWH.

Methods: Data were obtained from the South Carolina Revenue and Fiscal Affairs (RFA) Office and the South Carolina Alzheimer's Disease Registry (N = 13,390). Multivariable logistic regression models were used to determine the association between age, gender, race, rurality, depression and encephalopathy, and AD/ADRD among PLWH.

Results: Among the study population (N = 13,390), 5% (n = 601) were found to have AD/ADRD. There was a dose-response relationship between age group and AD/ADRD whereas the age group increased, the association increased. For example, those who were aged 80 years and older were 80 times more likely to have AD/ADRD compared to those aged 18-29 years (aOR: 80.4; 95% CI: 40.2-160.8). Additionally, male sex (aOR: 1.3; 95% CI: 1.9-1.6) and encephalopathy (aOR: 2.4; 95% CI: 1.9-3.2) were positively associated with AD/ADRD for PLWH.

Conclusion: AD/ADRD interventions may be warranted among PLWH, especially among older adults, men, and those with encephalopathy. Future studies should examine potential pathways between clinical and sociodemographic characteristics and AD/ADRD among PLWH.

Objective: We assessed sex differences in hospitalization rates among people with HIV (PWH) and people without HIV (PWoH) in British Columbia (BC).

Methods: PWH and a 10% random sample of PWoH in BC aged ≥19 were followed from 04/01/2002 to 03/31/2020, using linked administrative Comparative Outcomes and Service Utilization Trends (COAST) study data. Hospitalizations were categorized by discharge diagnosis, using broad International Classification of Diseases-classes. Using Poisson regression, we modelled the association between sex, HIV-status, their interaction, and hospitalization rates adjusting for confounders.

Results: Among 12,635 PWH (17.81% females) and 548,992 PWoH (49.34% females), age-adjusted hospitalization rates per 100 person-years were highest among females with HIV (incidence rate [IR] 34.25), followed by males with HIV (IR 21.49), females (IR 7.10), and males (IR 7.06) without HIV. Hospitalization rates for all causes declined from 2002-2022 across all subgroups but remained consistently higher among females with HIV, except for circulatory diseases and neoplasms. Adjusted for socio-structural factors, being male (rate ratio [RR] 1.92) or female with HIV (RR 2.66) was significantly associated with a higher hospitalization rate compared to males without HIV. Among PWH, female sex remained significantly associated with a higher hospitalization rate, after adjusting for HIV- and disease-related factors.

Conclusions: We found a higher hospitalization rate among PWH than PWoH in BC, with the highest rate among females with HIV. This could partially be explained by socio-structural factors. Addressing these disparities and improving our understanding of the underlying mechanisms is critical to enhance health outcomes for women with HIV.

Objectives: Albuvirtide (ABT) is a long-acting fusion inhibitor. This study assessed switching to ABT 640 mg every 4 weeks plus daily Dolutegravir (DTG) in virologically suppressed adults with HIV-1.

Design and methods: In this open-label, single-arm study, 10 participants with HIV-1 RNA <50 copies/mL switched to ABT plus DTG for 24 weeks. Safety, pharmacokinetics, viral load, and CD4+ T cell counts were assessed.

Results: No serious adverse events occurred. Albuvirtide's steady-state trough concentration was 31.1 times higher than PA-IC90. All participants maintained virological suppression. CD4+ T-cell counts increased significantly after 24 weeks (P = 0.0462).

Conclusion: Switching to 4-weekly ABT plus daily DTG demonstrated good safety, favorable pharmacokinetics, maintained virological suppression, and improved immune recovery. These findings support ABT's potential as a long-acting agent for simplifying HIV treatment.