Objective: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA).
Design: Site-level survey conducted in 2020-2021 among HIV clinics in low- and middle-income countries (LMICs).
Methods: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for patients on ART switching to dolutegravir-based regimens. We used generalized estimating equations to assess associations between clinic rollout of both first- and second-line dolutegravir-based ART regimens (dual rollout) and site-level factors.
Results: Of 179 surveyed clinics, 175 (98%) participated; 137 (78%) from Africa, 30 (17%) from the Asia-Pacific, and 8 (5%) from Latin America. Most clinics (80%) were in low- or lower-middle-income countries, and there were a mix of primary-, secondary- and tertiary-level clinics. Ninety percent reported rollout of first-line dolutegravir, 59% of second-line, 94% of first- or second-line and 55% of dual rollout. The adjusted odds of dual rollout were higher among tertiary-level (aOR 4.00; 95% CI 1.39 to 11.47) and secondary-level clinics (aOR 3.66; 95% CI 2.19 to 6.11) than in primary-level clinics. Over half (59%) of clinics that introduced first- or second-line dolutegravir-based ART required recent viral load testing before switching to dolutegravir, and 15% performed genotypic resistance testing at switch.
Conclusions: Dolutegravir-based ART was rolled out at nearly all IeDEA clinics in LMICs, yet many switched patients to dolutegravir without recent viral load testing and drug resistance testing was rarely performed. Without such testing, drug resistance among patient switching to dolutegravir may go undetected.
Background: Low food security is common among people with HIV (PWH) and is associated with poorer health outcomes. Frailty, an aging-related outcome that is increasingly prevalent among PWH, may be stimulated by low food security. We assessed associations between food security and frailty among PWH.
Methods: The Impact of Physical Activity Routines and Dietary Intake on the Longitudinal Symptom Experience of People Living with HIV (PROSPER-HIV) study follows PWH to evaluate how diet and physical activity impact symptoms. We utilized food security and frailty data from PROSPER-HIV Year 1 visits (January 2019 to July 2022) to estimate associations. Food security was measured via the validated two-item Food Security Questionnaire and categorized as Food Secure, Low Food Security, or Very Low Food Security. Frailty was measured with the Fried frailty phenotype, and categorized as robust, prefrail, and frail. We used relative risk regression to estimate associations between food security and frailty status, adjusted for demographic characteristics.
Results: Among 574 PWH, nearly one-quarter were women (22%), mean age was 52 years old, 8% were frail, and 46% prefrail. Low food security was reported among nearly one-third of PWH: 13% Low Food Security and 18% Very Low Food Security. Compared with being Food Secure, we found Low Food Security was associated with frailty [prevalence ratio: 4.06 (95% confidence interval (CI) 2.16-7.62] and Very Low Food Security was associated with both prefrailty [1.48 (1.23-1.78)] and frailty [5.61 (3.14-10.0)], as compared with robust status.
Conclusion: Low food security was associated with increased frailty among PWH in this study, suggesting a potential intervention point to promote healthy aging.
Background: Men who inject drugs who have sex with men (MWIDSM) may acquire HIV through injecting drugs or sex. Interventions to increase awareness of HIV preexposure prophylaxis (PrEP) have focused on gay/bisexual MSM and may not be reaching heterosexual-identifying men or people who inject drugs (PWID). We explored changes in PrEP awareness and use among MWIDSM from 2018 to 2022 by sexual identity.
Methods: We used data from the 2018 and 2022 National HIV Behavioral Surveillance among PWID recruited via respondent-driven sampling in 19 urban areas in the US. We examined changes in PrEP awareness and use over time by sexual identity among HIV-negative men who inject drugs and who had sex with another man in the past 12 months using log-linked Poisson regression models with robust standard errors with an interaction term between year and sexual identity.
Results: Among 758 HIV-negative MWIDSM (463 in 2018; 295 in 2022), nearly all sample participants were likely indicated for PrEP (94.2 and 92.9%, respectively). PrEP awareness increased from 2018 to 2022 among gay/bisexual-identifying MWIDSM [45.5-65.5%; aPR = 1.49, 95% confidence interval (95% CI) = 1.30-1.70] but remained stable for heterosexual-identifying MWIDSM (39.4-40.8%; aPR = 1.01, 95% CI 0.75-1.36). PrEP use remained low among all MWIDSM (2.5-7.7%, among heterosexually identifying; 15.3 to 10.2% among gay/bisexual-identifying).
Conclusion: PrEP awareness increased among gay/bisexual-identifying MWIDSM but not among heterosexual-identifying. PrEP use was low for all MWIDSM. Public health initiatives catered to MWIDSM should focus on improved campaigns and expanding PrEP accessibility in existing healthcare, harm reduction, and social services.
Objective: To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in U.S. women living with HIV (WLWH).
Design: We adapted a previously published Markov decision model to simulate a cohort of U.S. WLWH.
Setting: United States.
Subjects, participants: A hypothetical inception cohort of WLWH.
Intervention: We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21 to 29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage.
Main outcome measures: The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years.
Results: Compared with no screening, screening was cost-saving, and > 96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250,000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations.
Conclusions: Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing.
We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g. PD-1, CD27+, CD40+) in untreated HIV patients. Notably, soluble TIM-3 correlated positively with improved beta cell function and inversely with beta cell stress, suggesting its potential role in beta cell protection in untreated HIV.
This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].
Objective: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes.
Design: Longitudinal cohort study.
Methods: We included PWH aged ≥18 years from the Johns Hopkins HIV Clinical Cohort (2007-2023) without history of diabetes who had used NNRTI or PI for ≥180 days. We followed participants up to 10 years from HIV primary care visits where they switched to INSTI or continued NNRTI or PI. We estimated the hazard of incident diabetes associated with switching to INSTI using weighted Cox regression with robust variance estimator.
Results: We included 2075 PWH who attended 22 116 visits where they continued NNRTI or PI and 631 visits where they switched to INSTI. Switching to INSTI was associated with a weighted hazard ratio (wHR) of 1.11 [95% confidence interval (CI), 0.77-1.59] for incident diabetes. The association if no weight gain occurred during the first two years was not qualitatively different (wHR 1.22; 95% CI, 0.82-1.80). In a posthoc analysis, switching to INSTI conferred a significant wHR of 1.79 (95% CI, 1.13-2.84) for diabetes within the first two years but not after.
Conclusions: Switching from NNRTI or PI to INSTI did not significantly increase overall diabetes incidence in PWH, although there may be elevated risk in the first two years. These findings can inform considerations when switching to INSTI-based regimens.
Introduction: The window period, defined as HIV nucleic acid test (NAT) reactivity but Western blot (WB) test inconclusive, is garnering more attention. Improving the detection efficiency of HIV high-risk populations in the window period is critical to reducing the risk of unanticipated transmission. The purpose of this study was to create an additional strategy for distinguishing indeterminate HIV infection cases.
Methods: Based on WB follow-up results, the individuals in this study were divided into persons in the HIV window period and persons without HIV. Plasma was analyzed using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect differentially expressed proteins (DEPs). The biological implications of these DEPs were investigated using enrichment analysis. Protein-protein interaction (PPI) analysis and LASSO regression were used to identify key proteins. The calibration curve, decision curve, and nomogram were utilized to create the model.
Results: Fifty-seven DEPs were screened out, with 33 up-regulated and 24 down-regulated in persons with HIV at window period. The most important Gene Ontology (GO) enrichment items are oxidoreductase activity and heme binding. Oxidoreductases account for half of the 10 main proteins identified from various DEPs. An auxiliary diagnostic model comprised of peroxiredoxin-2 (P32119), band 3 anion transport protein (P02730), and histone H2A type 1 (P0C0S8) was developed. The results of the confusion matrix parameters revealed that this diagnostic approach had strong practicability in distinguishing indeterminate HIV infection cases.
Conclusions: The three DEPs identified and predicted by proteomics are useful for the supplemental identification of persons in the HIV window period.
Background: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower preexposure prophylaxis (PrEP) adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS).
Methods: YMSM/TGW participants ( n = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/ml) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days.
Results: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (<4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation [adjusted odds ratio (AOR) 6.1; 95% confidence interval (CI): 1.4-11; P = 0.005] and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value.
Conclusions: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.