Introduction: In sub-Saharan Africa, cisgender men-in particular men who have sex with women (MSW) and, to a lesser degree, men who have sex with men (MSM)-are often under-represented in HIV prevention research, despite their own HIV risk and role in transmission cycles. As HIV prevention research on long-acting pre-exposure prophylaxis (LA PrEP) options expands in sub-Saharan Africa, it is essential to engage these populations to ensure their acceptability. We investigated perceptions of implants and intramuscular injectables as LA PrEP delivery among MSW and MSM.
Methods: In-depth interviews were conducted between October 2020 and March 2021 with 40 MSW (n = 20) and MSM (n = 20), aged 18-35 years, self-reported as HIV negative, sexually active, and residing in resource-restricted communities in Cape Town and Johannesburg, South Africa. We explored factors influencing LA PrEP attitudes. Data analysis followed a thematic framework approach.
Results: MSW and MSM found LA PrEP administration modes more acceptable than daily oral PrEP because they offered longer lasting protection while reducing frequent clinic visits for refills. MSW voiced hesitancy around the use of "foreign products," fearing infertility and congenital disabilities in their future children. Both subgroups acknowledged the convenience of implants with long-dosing duration, but injections were deemed to be more discrete and familiar. Both groups described implant use as potentially stigmatizing, with a greater chance of causing tissue scarring from insertion and removal procedures.
Conclusions: Evidence relating to men's engagement in HIV prevention and acceptable modalities of HIV prevention is limited. We found that both groups were enthusiastic about LA PrEP, informing the development of our subsequent clinical study to provide further insight into using placebo versions of LA PrEP and future implementation of LA PrEP options.
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 the DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD studies (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 the DRIVE-AHEAD and DRIVE-FORWARD studies, 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 that DOR-based therapy may be a good option for adults with baseline neuropsychiatric symptoms or those experiencing NPAEs with other antiretrovirals.
Introduction: Florida remains a high-incidence, high-prevalence setting for HIV. Long-acting (LA) antiretroviral therapies (ART) could improve HIV-related outcomes and reduce transmission. This study identifies preferred LA ART characteristics and classes of preference among persons with HIV (PWH) in Florida.
Methods: The Florida Cohort enrolls adult PWH from 6 counties. In February 2023, a best-worst scaling discrete choice experiment was added that included 12 tasks with 3 alternatives and an opt-out (i.e., their current regimen). Six attributes were included: treatment type (e.g., shot), long-term effects, side effects, location (e.g., at home), effectiveness, and frequency. A Hierarchical Bayes model was used to estimate level utilities, attribute importance was calculated, and a latent class model was run in Sawtooth Software.
Results: Overall, 208 PWH participated (60% aged 50+, 49% non-Hispanic Black, 54% male). Treatment type had the greatest impact on preference [27.2% (95% CI: 25.1 to 29.3)], followed by frequency [23.4% (95% CI: 21.6 to 25.2)], and long-term effects [19.0% (95% CI: 17.8 to 20.3)]. Within treatment type, LA pills were preferred over other options, including their current regimen. Less frequent administration was preferred, but only yearly administration was preferred over their current regimen. Within long-term effects, participants preferred no increase in risk. Two classes were identified where one class (27% of participants) preferred their current regimen and the other (73% of participants) preferred an alternative, placing greater importance on frequency.
Conclusions: PWH preferred LA pills and less frequent administration, so future ART development could focus on options with these traits. Further exploration of user preference classes is needed.
Background: In 2019, there were an estimated 1.2 million persons with HIV (PWH) and 35,100 new infections in the United States. The HIV care continuum has a large influence on transmission dynamics.
Methods: We updated Progression and Transmission of HIV 3.0, an agent-based simulation model, to estimate 2019 HIV transmission rates and distribution of transmissions by the HIV care continuum, race/ethnicity, transmission group, and age group.
Results: In 2019, the estimated transmission rate in the United States was 2.94 new infections per 100 person-years ( inf/100p-y) . Transmission rates decreased along the HIV care continuum; the highest transmission rate was associated with persons with acute HIV infection and unaware of their HIV status at 16.35 inf/100p-y , followed by PWH (nonacute) and unaware of their HIV status (9.52), persons aware of their HIV status and not in care (5.96), persons receiving HIV care (on antiretroviral therapy) but not virally suppressed (4.53), and persons virally suppressed (0). The highest transmission rate by transmission group was among men who have sex with men at 3.68 inf/100p-y . Transmission rates decreased as age increased and are similar by race/ethnicity, after accounting for the HIV care continuum.
Conclusions: Our results support a continued emphasis on helping PWH move along the care continuum through early diagnosis, linkage to care, and adherence to ART, resulting in viral suppression to reduce HIV transmissions. Furthermore, efforts should focus on reducing disparities in the provision of HIV prevention and care services, particularly for populations disproportionally affected by HIV.
Background: Pulmonary complications in people living with HIV (PWH) have shifted away from infectious disease and towards chronic disease. HIV is an independent risk factor for chronic obstructive pulmonary disease (COPD), with PWH developing COPD younger and declining faster in pulmonary function. As an accelerated decline is associated with greater mortality, there is a need to identify individuals at high risk of longitudinal decline.
Setting: 59 adults with HIV enrolled from the Pittsburgh Lung HIV study cohort.
Methods: Targeted metabolite profiling was performed on baseline bronchoalveolar lavage fluid (BALF, n=35) and serum samples (n=54) using liquid chromatography-high resolution mass spectrometry. Longitudinal pulmonary function tests (median 3 measurements over 2.95 years with a follow-up interval of 1.34 years) were used to determine rates of decline. Predictive modeling and feature selection algorithms identified baseline clinical and metabolomic factors associated with longitudinal decline across forced expiratory volume, forced vital capacity, and diffusing capacity of the lung.
Results: Predictive models found the BALF metabolome to successfully predict outcomes more consistently than serum. Key BALF metabolites such as elevated carnitine and reduced pyruvate predicted greater risk of longitudinal decline. Low serum citrate levels were a robust predictor of decline across multiple tests. Probabilistic graphical models supported direct relationships between these metabolites and lung function decline.
Conclusion: Baseline metabolomic profiling, especially using BALF, can help identify PWH at risk for accelerated lung function decline. Key metabolic pathways related to glucose oxidation, fatty acid metabolism, and amino acid metabolism underlie observed lung function changes.
Objective: We sought to characterize the frequency of amyloid-PET positivity among older cognitively impaired people with HIV (PWH) compared to cognitively unimpaired people without HIV (PWoH). We also examined the neuropsychological profiles of the PWH group by amyloid-PET status, cross-sectionally and longitudinally.
Methods: Virally suppressed PWH were sought for a study of HAND where amyloid-PET positivity was used to exclude the possibility of AD. Participants underwent a standardized neuropsychological battery to diagnose HAND. Age and sex-matched cognitively unimpaired PWoH were identified from a separate cohort at our site. No participant from either group showed clinical signs and symptoms in a pattern concerning for AD. All participants completed amyloid-PET ([18F]Florbetapir). A certified neurologist visually read these as amyloid positive (PET+) or negative (PET-).
Results: Compared to cognitively unimpaired PWoH (n=65, mean age=67), the cognitively impaired PWH group (n=74, mean age=69) was predominantly male (94.6% vs. 72.3%, p<0.001), of non-hispanic white ethnicity (74.3% vs. 83.1%, p=0.211) and reported lower educational attainment (16.2 vs. 17.4 years, p<0.001). Among them, 6 (8.1%) had PET+ scans compared to 14 PWoH (21.5 %, p=0.024). Within the PWH group, we did not identify differences in the neuropsychological testing pattern by amyloid-PET status (all p-values >0.05).
Conclusion: Cognitively impaired PWH did not show increased frequency of amyloid positivity relative to cognitively unimpaired PWoH. Among PWH, cognitive performance did not differ by amyloid-PET status in analyses of cross-sectional baseline and longitudinal performance.
Background: We evaluated the relationship between maternal HIV and birth outcomes in pregnant women.
Setting: Primary health care facilities in Malawi.
Methods: In this prospective cohort study, pregnant women attending their first antenatal care (ANC) visit between 20-36 weeks gestation were categorized by HIV status. Women living with HIV were grouped by HIV viral load at ANC and delivery (detectable >400 copies/mL), CD4+ count at delivery (low <250 cells/mm3), and ART regimen (tenofovir- and efavirenz-based ART). We evaluated low birth weight (LBW, <2500g), preterm birth (PTB, <37 weeks gestation), small for gestational age (SGA, <10th percentile for gestational age), fetal death (pregnancy loss >28 weeks gestation), and perinatal death (<7 days) at delivery using multivariate log-binomial regression.
Results: We enrolled 1208 pregnant women (633 and 575 living with and without HIV, respectively) from 2018-2022. HIV was significantly associated with increased risk of fetal or perinatal death (adjusted risk ratio (aRR) 2.09, 95% CI 1.21, 3.70), LBW (aRR 1.88, 95% CI 1.30, 2.76), and PTB (aRR 1.49, 95% CI ( 1.07, 2.09). The strength of the association with LBW increased with increasing exposure to viral load, with an aRR of 2.35 (1.01, 3.99) for LBW among women with detectable viral loads throughout pregnancy. Low CD4+ count at delivery was associated with LBW. HIV was not significantly associated with SGA. Adverse birth outcomes did not differ by ART regimen.
Conclusion: Maternal HIV infection is a risk factor for adverse birth outcomes and the effect is partially mitigated by viral suppression.
Background: Frailty screening in HIV care has been recommended, however, screening adds burden to busy clinics. We compared criteria that predict concurrent frailty to identify approaches to optimally target frailty screening.
Methods: The development cohort included people with HIV (PWH) at six U.S. sites. Frailty was assessed based on four components of a modified Fried phenotype: fatigue, unintentional weight loss, low mobility, and poor physical activity. We evaluated demographic and clinical characteristics, comorbidities, and substance use as predictors of who should be screened using selection approaches for simple and complex frailty screening tools, including machine learning approaches. We compared discrimination and calibration including area under the receiver operator characteristic (ROC) curve (AUC), sensitivity, and specificity in a validation cohort (7th site).
Results: Among the 9,592 PWH in the development cohort, 11% were frail. AUC ranged from 0.52 for simple screening approaches such as age-based to 0.84 for complex approaches in the development and validation cohorts. Using an age cutoff >50 years reduced the percentage of PWH needing screening by over half but also reduced the sensitivity to 58% in the validation cohort. Complex approaches required 47% to be screened and had a sensitivity of 89%.
Conclusions: Age-based frailty screening approaches (e.g., >50 years) miss many frail PWH. Complex tools had marginally better testing characteristics but would be more difficult to implement in clinical care. Simple targeted screening based on three characteristics (age, gender, and depressive symptoms) identified 89% of frail PWH and reduced the number who needed screened by 52%.
Background: We reported immunological and virologic outcomes within 10 years of combined Antiretroviral Therapy (cART) initiated no later than age one year and associated factors in children with perinatal HIV in Cameroon.
Setting: This study was conducted in 3 referral hospitals in Cameroon.
Methods: We conducted a prospective cohort study, using time-to-event analysis. Probabilities of the following outcomes were assessed within the first 10 years of cART initiation: first Viral Suppression to <400 copies/mL (VS), maintaining first VS, Immunocompetence (IC) - stage 1, CDC Immunological Classification - and mortality.
Results: 190 children started cART before one year of age, at an average age of 4.3 months (Standard deviation: ±2.5 months), of whom 45.3% were immunocompetent; 66.8% on nevirapine (NVP)-based versus ritonavir-boosted lopinavir (LPV/r)-based regimens; 37.9% with running water at home. At 10 years of cART initiation, outcomes probabilities estimates were: 22.0% of death mostly in the first 2 years and mainly due to advanced HIV disease, 72.0% of first VS achieved; 70.0% and 50.4% of first VS maintained considering children with first VS achieved and all the study participants, respectively; immunocompetent children increased to 88.6%. Being immunocompetent at cART initiation and receiving LPV/r-based regimens (versus NVP-based ones) over time were significantly associated with maintaining VS.
Conclusion: Long term efficacy of early cART in children with perinatal HIV was mainly impaired by high mortality during initial phase. Screening strategies, even community-based, for early detecting HIV in exposed infants before advanced HIV disease had set up, should be implemented.
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