JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: In the United States, up to 75% of primary care patients go untested for HIV each year, and nearly two-thirds of adults report never having been tested for HIV. Integrated HIV and STI testing, combining these tests into a single visit, is recommended as a status neutral approach to prevention.

Setting: Over 200 New York State Department of Health-funded primary care clinics, hospitals, health centers and community-based organizations funded to conduct integrated screening.

Methods: We analyzed weekly testing data from December 2022 to January 2024 to prospectively evaluate whether integrated HIV and STI testing events and results occurred within 30 days of each other. We also assessed group differences in integrated testing by sex at birth, gender, race/ethnicity, risk, organization type, and pre-exposure prophylaxis (PrEP) status using Pearson's Chi-square tests and calculated prevalence ratios using log binomial models stratified be PrEP usage. Analyses were restricted to individuals with an HIV-negative status.

Results: Integrated testing was completed for 69% for individuals on PrEP and 39% for those not taking PrEP, with significant differences observed across all client-specific categories at p < 0.001. Except for age group, variations in integrated screening levels by client characteristics were similar by PrEP status. Individuals who identified as female at birth, as non-Hispanic Black, without an elevated risk, and those tested in non-hospital settings were significantly less likely to experience integrated screening. HIV-test reactivity was 0.04% among integrated testers and 0.15% for HIV-only testers. STI-test reactivity was 4.9% among integrated testers and 7.8% for STI-only testers.

Conclusions: A significant gap was identified in integrated testing among providers specifically funded to perform it, resulting in missed opportunities for identification of HIV and other sexually transmitted infections. Integrating HIV and STI testing at a systems level will require significant changes to the perceived individual- and provider-level risks and benefits associated with testing.

Background: Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

Methods: In DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD (NCT02275780), treatment-naive adults randomly received DOR/lamivudine/TDF or EFV/FTC/TDF and DOR + 2 NRTIs or DRV/r + 2 NRTIs, respectively, for a 96-week double-blind phase; afterward, participants could continue or switch to a DOR-based regimen for a 96-week open-label extension.

Results: Overall, 269 and 233 participants in DRIVE-AHEAD and DRIVE-FORWARD, respectively, switched to a DOR-based regimen. At Week 96, 26 and 15 participants randomized to EFV/FTC/TDF and DRV/r + 2 NRTIs, respectively, had ongoing NPAEs, resolving by Week 192 in 73% (19/26) and 40% (6/15) of participants switching to a DOR-based regimen. New-onset NPAEs were reported by 9% (25/269) and 8% (18/233) of participants; by Week 192, new-onset NPAEs were resolved and/or resolving in 60% (15/25) and 61% (11/18) of participants.

Conclusions: In both trial extensions, NPAEs persisted in 3-4% of participants 96 weeks after switching to a DOR-based regimen, possibly representing the background rate for these events. This suggests DOR-based therapy may be a good option for adults with baseline neuropsychiatric symptoms or those experiencing NPAEs with other antiretrovirals.

Introduction: Little is known about the clinical status of persons with HIV (PWH) who re-engage in care after an interruption. We evaluated the immunological and clinical characteristics of individuals re-engaging in care within the Swiss HIV Cohort Study.

Methods: Participants who re-engaged in care after an interruption >14 months with a viral load ≥100 copies/mL were classified as having interrupted ART. We defined late re-engagement as re-engaging with a CD4 cell count of <350 cells/µL or a new CDC stage C disease. Linear and logistic regression models with restricted cubic splines were used to estimate the mean CD4 cell count at re-engagement and the probability of late re-engagement as a function of care interruption duration.

Results: Of 14,864 participants with a median follow-up of 10.2 years (IQR 4.7-17.2 years), 2,768 (18.6%) interrupted care, of whom 1,489 (53.8%) re-engaged. Among those re-engaging, 62.3% had interrupted ART. For participants who interrupted ART, the mean CD4 count declined from 374 cells/µL (95% CI 358-391 cells/µL) before the interruption to 250 cells/µL (95% CI 221-281 cells/µL) among those re-engaging after 14 months, and to 185 cells/µL (95% CI 160-212 cells/µL) among those re-engaging after 60 months. The estimated risk of late re-engagement in care was 68.6% (95% CI 62.3-74.4%) for participants who interrupted ART for 14 months and 75.2% (95% CI 68.9-80.6%) for those who interrupted ART for 60 months.

Conclusion: Although HIV care interruptions are not very common in Switzerland, the majority of PWH re-engaging after interrupting ART return with late-stage HIV.

Background: Data on tuberculosis (TB) incidence and risk factors among children living with HIV (CLHIV) in the universal ART era are limited.

Methods: We analysed routinely-collected data on TB diagnoses for CLHIV age ≤5 years, born 2018-2022, in the Westen Cape, South Africa. We examined factors associated with TB diagnosis, with death and loss to follow-up as competing events.

Results: Among 2,219 CLHIV, 30% were diagnosed with HIV at birth. Median follow-up from birth was 38 months (IQR 24-50); 90% started antiretroviral therapy (ART). TB was diagnosed in 28% of CLHIV (n=626/2219); 62% were first diagnosed before/within 3 months of ART start ('TB before ART') and 38% >3 months after ART start ('TB after ART'). Of those with 'TB before ART' (n=390), median age at HIV diagnosis was 13 months (IQR:6-22); median time between HIV and TB diagnoses was 5 days (IQR:0-31). 'TB before ART' was associated with older age at HIV diagnosis and advanced/severe immunodeficiency. Of those with 'TB after ART' (n=258), median age at HIV diagnosis was 2 months (IQR 0-8) and median time from ART start to TB diagnosis was 12 months (IQR:7-21). 'TB after ART' was associated with increased viral load and advanced/severe immunosuppression (time-updated). Overall, 5% (n=112/2219) of CLHIV died, 36% of whom were diagnosed with TB (median time from TB diagnosis to death: 58 days; IQR:17-191).

Conclusions: Young CLHIV in this setting have high TB-associated morbidity and mortality. Efforts to improve early HIV and TB diagnosis, viral suppression and TB preventive therapy are needed.

Introduction: Few data are available about the forgiveness of two-drug (2DR) or low-barrier three-drug antiretroviral regimens. The aim of this study is to evaluate the real-life forgiveness of lamivudine/dolutegravir (3TC/DTG) and emtricitabine/tenofovir alafenamide/rilpivirine (FTC/TAF/RPV).

Methods: A two center retrospective observational study enrolled all people with HIV (PWH) treated with 3TC/DTG or FTC/TAF/RPV. Adherence was measured as the proportion of days covered (PDC) by drug supply. Binary logistic regression was applied to test the impact of baseline variables and adherence on the achievement of virological suppression.

Results: 1258 adult PWH were enrolled, 368 in 3TC/DTG and 890 in RPV/F/TAF. Most were males (71 %), with median age of 51 years (IQR 43-58 years) and median CD4 nadir of 305 cells/mcL (IQR 132-485). The median cohort follow-up totaled 4558 persons/year. Median adherence, as calculated from PDC, was of 0.98 (IQR 0.93-1). Irrespective of the treatment group, a PDC as low as 0.8 was sufficient to obtain HIV-RNA below 200 copies/mL in almost all study participants. The same adherence value also allowed the achievement of HIV-RNA below 50 copies/mL in > 90% of study participants. PDC (P < 0.0001), Italian origin (P < 0.0001) and male sex (P = 0.038) significantly correlated to the achievement of < 200 copies/mL.

Conclusions: In this study, we found a similar and high grade of forgiveness in the INSTI-based 2-drug regimen 3TC/DTG and in the NNRTI-based 3-drug regimen FTC/TAF/RPV.

Objective: The objective of this study is to define the neuropsychiatric challenges including developmental delay, cognitive impairment and psychiatric illness faced by children with perinatally acquired HIV.

Data sources: Nine databases were searched on 30/05/2023: MEDLINE, Embase, and PsycINFO (all via Ovid SP); CINAHL and Child Development and Adolescent Studies (via EBSCO); the Web of Science Core Collection; Scopus; ProQuest Dissertations and Theses Global; and WHO Global Index Medicus. No limits were applied. Search strategies incorporated keywords and thesaurus headings to describe children and adolescents aged 0-25 with perinatally acquired HIV and terms to describe the spectrum of neuropsychiatric impairment.

Study selection: Entries were reviewed by two independent reviewers. Studies were included if they involved a population of children with perinatally acquired HIV and investigated a neurological or psychiatric outcome.

Main outcome measures: Hypothesis that children with pHIV would have more neuropsychiatric challenges than children without pHIV was formulated before the study. Main outcome measures include incidence and severity of cognitive impairment, developmental delay and psychiatric illness in children with pHIV.

Results: 45 studies on cognitive impairment were included of which eight studies were included for meta-analysis and demonstrated a standardised mean difference of -0.508 where children without HIV had higher cognitive scores (95% CI -0.7903; -0.2272). 15 studies on developmental delay were included of which nine were included for meta-analysis and demonstrated, for motor delay, a standardised mean difference (SMD) of -0.794 where children without HIV achieved higher motor function scores (95% CI: -0.9986 to -0.590; ) and for cognitive delay a SMD of -0.697 where children without HIV achieved higher cognitive function scores (CI -0.976 to -0.417;). 39 studies on psychiatric illness were included with an odds ratio for anxiety and depression of 1.105, suggesting that children with HIV had slightly higher odds of developing anxiety or depression, however this result was not significant (CI: 0.778 - 1.571).

Conclusions: Children with perinatally acquired HIV may have a greater cognitive impairment, motor and cognitive delay and would likely benefit from tailored approaches to improve their outcomes.

Background: Loss to follow-up to HIV care following delivery puts birthing parents with HIV at higher risk of loss of viral suppression, disease progression, and HIV partner transmission. This study assessed factors associated with retention in postpartum HIV care.

Methods: This is a retrospective cohort study at a single academic medical center and included patients followed from January 2014 to December 2022. The primary outcome was retention in postpartum HIV care (any healthcare encounter discussing HIV medication adherence or viral load within 12 months postpartum). Data was analyzed using Chi-square and student T-test for discrete and continuous variables. Univariate and multivariable log regressions were used to measure independent associations on care retention and healthcare utilization outcomes.

Results: Of the 111 patients with planned follow up at our facility, 93 (83.8%) of participants had ≥ 1 HIV care encounter within 12 months of delivery. Participants had a mean age of 31.2 (± 5.84), were predominantly Black (79.3%), non-Hispanic (91%), non-U.S. born (57.5%) with substantial exposure of prior IPV (29.6%). Participants retained in care were more likely to use ART during pregnancy (92/99% vs 16/94.2%, P=0.01) and have viral suppression at delivery (n= 83/90% vs 12/67%, P=.02). Retention in care was negatively associated with substance use during pregnancy (aOR 0.29, 95% CI 0.09-0.95) following adjustment for social health covariates.

Conclusion: While almost 84% of participants were retained in HIV care within 12 months of delivery, substance use in pregnancy was a significant risk factor for HIV care attrition postpartum.

Introduction: We assessed the risk of adverse pregnancy and birth outcomes and birth defects among women living with HIV (WLHIV) on antiretroviral therapy (ART) and HIV-negative women.

Methods: We analyzed data on live births, stillbirths, and spontaneous abortions during 2015-2021 from a hospital-based birth defects surveillance system in Kampala, Uganda. ART regimens were recorded from hospital records and maternal self-reports. Using a log-binomial regression model, we compared the prevalence of 16 major external birth defects and other adverse birth outcomes among WLHIV on ART and HIV-negative women.

Results: A total of 203,092 births were included from 196,373 women of which 15,020 (7.6%) were WLHIV on ART. During pregnancy, 15,566 infants were primarily exposed to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART (n=13,614; 87.5%). After adjusting for maternal age, parity, and number of antenatal care (ANC) visits, WLHIV on NNRTI were more likely than HIV-negative women to deliver preterm (adjusted prevalence ratio [aPR]=1.27, 95% confidence interval [CI]: 1.21,1.32), post-term (aPR=1.23, 95% CI: 1.16,1.32), or small for gestational age infants (aPR=1.35, 95% CI: 1.30,1.40). Spina bifida was more prevalent among infants born to WLHIV on ART periconceptionally compared to HIV-negative women (aPR=2.45, 95% CI 1.27,4.33). The prevalence of the other selected birth defects were similar between infants from WLHIV on ART and HIV-negative women.

Conclusion: In Uganda, WLHIV on ART were more likely than HIV-negative women to experience selected adverse birth outcomes. Further surveillance of maternal ART exposure, including by drug class and ART regimen, is needed to monitor and prevent adverse birth outcomes in WLHIV.

Background: HIV drug resistance can reduce the effectiveness of antiretroviral drugs in preventing morbidity and mortality, limit options for treatment, and prevention. Our study aimed to assess HIV-1 subtypes and HIV drug resistance among key populations in HIV Sentinel Surveillance Plus Behavior in 2018 and 2020.

Methods: One-stage venue-based cluster sampling was used to recruit participants at hotspots identified for men who have sex with men (MSM) in 7 provinces and sexual minority females and female sex workers (FSW) in 13 provinces. Participants completed a standard questionnaire about risk and preventive behaviors, and antiretroviral therapy history, and provided intravenous blood for HIV testing. HIV drug resistance testing was conducted on HIV-positive samples with viral load >1000 copies/mL.

Results: A total of 185 of 435 (42.5%) HIV-positive samples had viral load ≥1000 copies/mL, of which 130 of 136 from MSM and 26 of 49 from FSW were successfully sequenced. Six HIV-1 subtypes were detected (CRF01_AE, A, CRF07/08_BC, B, C, CRF25_cpx), with CRF01_AE (82.7%, 129/156) the most common. Drug resistance mutations were detected in 16.7% of participants overall (26/156), in 15.4% (20/130) of MSM, and in 23.1% (6/26) of FSW. Mutations associated with resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) were the most frequently detected (73.1%, 19/26). The high level of resistance was presented in NNRTI and nucleoside reverse transcriptase inhibitors classes. There are 10 major resistance mutations detected with nucleoside reverse transcriptase inhibitors (M184VI-25.0%, K65KR-50.0%, Y115F-25%), NNRTI (K103N-21.1%, E138A-10.5%, V106M-5.3%, K101E-5.3%, G190A-5.3%), protease inhibitors (L33F-40.0%, M46L-20.0%).

Conclusions: Vietnam's HIV Sentinel Surveillance Plus system identified an emerging strain of HIV-1 and mutations associated with resistance to multiple drug classes among MSM and FSW.

Background: Case identification remains a challenge to reaching the United Nations 95-95-95 targets for children with HIV. Although the World Health Organization approved oral mucosal HIV self-testing (HIVST) for children older than 2 years in 2019, there is little information on HIVST for pediatric case identification in Ethiopia.

Setting: Nine health facilities across Ethiopia.

Methods: We implemented a pilot program from November 2021 to April 2022 to assess acceptability and feasibility of using HIVST to screen children 2-14 years of adult index clients, (ie, parents/caregivers living with HIV and on antiretroviral therapy). HIV-positive adults who had children with unknown HIV status were given HIVST kits (OraQuick) to screen their children at home. Parents/caregivers were asked to report results telephonically and bring children screening positive to the health facility for confirmatory HIV testing. We defined HIVST acceptability as ≥50% of parents/caregivers accepting testing and ≥50% reporting results within 7 days of receiving a test kit. Feasibility was defined as ≥60% of children with a reactive HIVST receiving confirmatory testing and <5 serious social harms reported per 1000 kits distributed.

Results: Overall, 1496 of 1651 (91%) parents/caregivers accepted HIVST kits to test their children at home and 1204 (71%) reported results within 7 days. Of 17 children (1%) with reactive results, 13 (76%) received confirmatory testing; of which 7 (54%) were confirmed to be HIV positive. One serious social harm was reported.

Conclusions: Providing adult parents/caregivers with HIVST kits to screen their children at home is an acceptable and feasible strategy to reach untested children and improve pediatric case finding in a low prevalence setting.