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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.

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: 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.

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: 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/m2 (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.

Objective: Increasingly, pregnant women living with HIV (WLHIV) initiate antiretroviral therapy (ART) before conception. We assessed the risk of adverse perinatal outcomes among pregnant WLHIV initiating ART preconception or antenatally, compared with women without HIV or ART-naïve WLHIV.

Design: Systematic review and meta-analysis.

Methods: We searched PubMed, EMBASE, CINAHL, and Global Health for studies published between 1/1/1980 and 14/7/2023. We assessed the association of preconception/antenatal ART initiation with preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), small-for-gestational-age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Data were analysed using random effects meta-analyses. Quality assessments, subgroup and sensitivity analyses were conducted. PROSPERO registration: CRD42021248987.

Results: Thirty-one cohort studies were eligible, including 199,156 women in 19 countries. WLHIV with preconception ART were associated with increased risk of PTB (risk ratio 1.55; 95%CI 1.27-1.90), VPTB (2.14,1.02-4.47), LBW (2.19, 1.32-3.63), VLBW (3.34, 1.08-10.35), SGA (1.92, 1.01-3.66), and VSGA (2.79, 1.04-7.47), compared with women without HIV. WLHIV with antenatal ART were associated with increased risk of PTB (1.35, 1.15-1.58), LBW (2.16, 1.39-3.34), VLBW (1.97, 1.01-3.84), SGA (1.77, 1.10-2.84), and VSGA (1.21, 1.09-1.33), compared with women without HIV. Compared to ART-naïve WLHIV, WLHIV with preconception or antenatal ART were associated with increased risk of SGA (preconception: 1.40, 1.12-1.73; antenatal: 1.39, 1.11-1.74) and VSGA (preconception: 2.44, 1.63-3.66; antenatal: 2.24, 1.48-3.40).

Conclusion: Among WLHIV, both preconception and antenatal initiation of ART are associated with increased risks of adverse perinatal outcomes, compared to women without HIV and ART-naïve WLHIV.

Objectives: Posttraumatic stress disorder (PTSD) may affect antiretroviral therapy (ART) response and clinical outcomes for veterans with HIV (VWH) receiving care in the Department of Veterans Affairs (VA). Objectives are to estimate the associations between PTSD and ART nonadherence, modifications, and failure; measure effect modification by number of deployments and combat exposure; and examine how these associations vary over time.

Design: In this prospective cohort study of all VWH on ART who deployed to Iraq and Afghanistan and receive care in the VA (n = 3206), patients entered at ART initiation and were censored in December 2022, totaling 22 261 person-years of follow-up.

Methods: Marginal structural log-binomial and Poisson models were fitted with a time-dependent exposure, adjusted for time-independent and time-dependent confounding and informative censoring, to estimate the associations between PTSD and ART nonadherence, modifications, and failure. Marginal structural shared frailty models were fitted to examine time-varying associations.

Results: PTSD increased the risk [adjusted risk ratio, 95% confidence interval (CI)] of ART nonadherence by 6% (1.06 [1.00, 1.13]) and the rate (adjusted incidence rate ratio, 95% CI) of ART modifications by 38% (1.38 [1.19, 1.58]). Multiple deployments amplified the association with ART nonadherence by 14%; combat exposure did not modify any association examined. The association with ART modifications increased during the first decade post-PTSD-diagnosis but subsequently stabilized.

Conclusions: PTSD increased ART nonadherence and ART modifications. Providers should screen for PTSD so that it can help guide medical decisions and treatment; particular attention should be paid to Veterans with multiple combat deployments.