JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Incomplete adherence to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) reduces effectiveness. Adherence biomeasures (i.e. drug concentrations in biological specimen) are more accurate than self-report. TDF/FTC's intracellular active metabolites (tenofovir-diphosphate; TFVdp and FTC-triphosphate; FTCtp) can be quantified in different types of blood samples to estimate adherence. To optimize adherence estimation, we investigated approaches to measure TFVdp and FTCtp in four blood matrices.

Methods: Twelve HIV-negative, healthy volunteers were enrolled in a single center, open-label, 3-phase, directly observed therapy study. LC-MS/MS methods quantified TFVdp/FTCtp in dried blood spots, volumetrically accurate microsampling, upper layer packed cells and peripheral blood mononuclear cells (PBMCs). Non-compartmental analysis estimated half-lives and accumulation ratios. Correlations characterized relationships between clinical variables and exposure. Regression models were fit to determine concentrations associated with <4 and ≥4 doses/week; correct classification percentages were determined.

Results: Terminal half-life estimates of 3-4 vs 15-22 days distinguished between moderate-term (FTCtp in all samples; TFVdp in PBMCs) versus long-term (TFVdp in red blood cell-containing matrices) measures. Model-derived thresholds accurately categorized <4 and ≥4 doses/week when including both metabolites for 14- and 28-day dosing periods (81-91% and 82-85%, respectively). Within each classification and regression trees analyses containing both moderate- and long-term measures, dried blood spots exhibited highest accuracy to predict stable (74-94%) and changing (42-47%) adherence patterns.

Conclusion: We demonstrate higher accuracy of moderate-term biomeasures to classify adherence over a 14-day period compared to long-term biomeasures to classify adherence over a 28-day period. Combined moderate- and long-term biomeasures predicted stable and changing adherence patterns, with dried blood spots exhibiting highest accuracy.

Background: HIV pre-exposure prophylaxis (PrEP) remains particularly underutilized among homeless-experienced people who use drugs (PWUD).

Setting: Boston Health Care for the Homeless Program, a Federally Qualified Health Center serving homeless-experienced individuals in Boston, Massachusetts.

Methods: To identify determinants of PrEP prescription initiation and continuation, we analyzed electronic medical records and pharmacy data between April 2018-March 2022. Participants were HIV-negative and reported sexual, drug, or community-related HIV exposures. Adjusted multinomial logistic regression explored associations between sociodemographics, social vulnerabilities, behavioral factors (e.g., injection drug use), and mental health and substance use disorder diagnoses with filling of one and more than one PrEP prescription.

Results: Among 509 participants, mean age was 38 years, 28% were women, 19% were Black, and 24% were Hispanic/Latino. At program enrollment, most were experiencing homelessness (92%), injecting drugs (78%), and living with a mental health disorder (71%). In multivariable-adjusted models, injection drug use was positively associated with filling one and more than one PrEP prescription (adjusted odds ratio [AOR]: 2.88, 95% confidence interval [CI]: 1.33-6.26; and AOR: 3.60, 95% CI: 2.02-6.42, respectively). Participants with opioid use disorder and generalized anxiety disorder were more likely to fill one and more than one prescription, while those with bipolar disorder were less likely to fill one prescription. No sociodemographic characteristics, sexual behaviors or other mental health or substance use disorders were associated with study outcomes.

Conclusion: A low-threshold, harm reduction-oriented PrEP program supported prescription initiation and continuation for homeless-experienced PWUD. Implementation research is needed to facilitate scale-up of this approach.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated LC-MS/MS methods. Within-participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between 2nd and 3rd trimester versus postpartum. Infant HIV testing results were obtained.

Results: Twenty-seven maternal-infant pairs enrolled. Bictegravir AUC0-24 was 46% lower in the 2nd trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43-0.69) and 52% lower in the 3rd trimester (n=24; P < 0.0001; GMR 0.48; 90% CI: 0.43-0.55), compared to postpartum. C24 concentrations were above the estimated bictegravir protein-adjusted EC95 of 0.162 µg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n=17; quartiles: 1.17, 1.63). Median T1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7, 45.9) with a Cmax of 2.06 µg/mL (quartiles: 1.37, 2.72). 88-92% of participants maintained suppression <40 copies/mL throughout pregnancy and postpartum. All available infant HIV testing results were negative. The safety profile for pregnant PWH and infants was acceptable.

Conclusions: Bictegravir exposure was lower during pregnancy compared to postpartum, yet C24 concentrations were greater than the bictegravir protein-adjusted EC95.

Background: Consistent evidence shows stigma impedes healthcare access in people living with HIV (PLWH) and men who have sex with men (MSM). We evaluated the impact of a stigma reduction training for providers whose design was informed by direct observation of their clinical behaviors obtained through visits by incognito standardized patient (SP).

Setting: We conducted this study in in sexually transmitted infection clinics in Guangzhou, China.

Methods: This pilot cluster randomized control trial assessed the feasibility, acceptability, and preliminary efficacy of an intervention whose design was informed by a baseline round of incognito visits in which SPs presented standardized cases to consenting doctors. By randomly varying the HIV status and sexual orientation of each case, we could quantify stigma as differences in care quality across scenarios. We then conducted a follow-up round of SP visits and assessed impact using linear fixed effects regression.

Results: Feasibility and acceptability among the 55 provider participants was high, with no adverse visit events. The training improved testing for HIV negative MSM (0.05 percentage points [PP], 95% CI,-0.24, 0.33) and diagnostic effort in HIV positive MSM (0.23 standard deviation [SD] improvement, 95% CI, -0.92, 1.37). Patient-centered care only improved for HIV positive straight cases (SD, 0.57; 95% CI, -0.39, 1.53). All estimates lacked statistical precision, an expected outcome of a pilot RCT.

Conclusions: Our training reduced stigma in in several domains of care, but least of all for PLWH, suggesting that future trainings should include more clinical content to strengthen clinical skills in PLWH management.

Introduction: The US state of Florida has the third highest rate of HIV as well as high rates of sexually transmitted infections (STIs) indicating critical HIV and STI prevention needs remain unmet. To address gaps in the STI care continuum in people with HIV (PWH), evidence-based interventions were implemented across three Ryan White HIV/AIDS Program (RWHAP) funded clinics in Florida between August 2020-August 2021. Interventions included comprehensive sexual health history (SHH) taking using audio computer-assisted self-interview (ACASI) software, self-collected extragenital gonorrhea and chlamydia testing, and the introduction of a lesbian, gay, bisexual, transgender, and queer (LGBTQ+) welcoming environment.

Methods: We 1) assessed the acceptability of these interventions and examined if acceptability differed among youth and sexual, racial and ethnic minorities, 2) determined the proportion of appropriate STI testing completed based on the SHH assessment, 3) examined whether STI at-risk individuals underwent STI screening 3-6 months after initial evaluation, and 4) determined the proportion of positive STI test results among priority intervention groups in Florida.

Results: Acceptability of all interventions was high. Youth, lesbian, gay, and bisexual, and Hispanic individuals were significantly more likely to notice and like LGTBQ+ welcoming measures. The proportion of recommended tests completed was high, although only a subset of at-risk individuals completed re-screening. 11.9% of rectal samples were positive for chlamydia and 6.5% of pharyngeal samples were positive for gonorrhea.

Conclusions: Our study highlights the importance of incorporating comprehensive sexual health care protocols, including extragenital STI testing, into the overall care of PWH.

Background: This study aims to develop and examine the performance of machine learning (ML) algorithms in predicting viral suppression among statewide people living with HIV (PWH) in South Carolina (SC).

Methods: Extracted through the electronic reporting system in SC, the study population was adult PWH who were diagnosed between 2005-2021. Viral suppression was defined as viral load <200 copies/ml. The predictors, includingsocio-demographics, a historical information of viral load indicators (e.g., viral rebound), comorbidities, healthcare utilization, and annual county-level factors (e.g., social vulnerability) were measured in each 4-month windows. Using historic information in different lag time windows (1-, 3- or 5-lagged time windows with each 4-month as a unit), both traditional and ML approaches (e.g., Long Short-Term Memory network [LSTM]) were applied to predict viral suppression. Comparisons of prediction performance between different models were assessed by area under curve (AUC), recall, precision, F1 score, and Youden index.

Results: Machine learning approaches outperformed the generalized linear mixed model. In all the three lagged analysis of a total of 15,580 PWH, the LSTM (lag 1: AUC=0.858; lag 3: AUC=0.877; lag 5: AUC=0.881) algorithm outperformed all the other methods in terms of AUC performance for predicting viral suppression. The top-ranking predictors that were common in different models included historical information of viral suppression, viral rebound, and viral blips in the Lag-1 time window. Inclusion of county level variables did not improve the model prediction accuracy.

Conclusion: Supervised machine learning algorithms may offer better performance for risk prediction of viral suppression than traditional statistical methods.

Background: In the United States, young men who have sex with men (YMSM) and young transgender women (YTGW) are disproportionately affected by HIV infection. Adequate HIV knowledge is critical for protecting adolescents and young adults at risk for HIV. This study aimed to evaluate the effectiveness of the mLab App intervention in enhancing HIV knowledge among YMSM and YTGW.

Methods: This study was a secondary analysis of data collected from a randomized controlled trial (RCT) evaluating the effect of the mLab App on HIV knowledge. We calculated interactions between groups (mLab App intervention, standard of care, at-home testing) over time (6 and 12 months) following the baseline observation, indicating a difference in the outcome scores from baseline to each time across groups.

Results: While the mLab App group initially had lower HIV knowledge compared to those in other groups, access to the App demonstrated a progressive impact on HIV knowledge over time. Despite the absence of a statistically significant effect at the 6-month, the long-term evaluation suggests improvements in HIV knowledge during the 12-month intervention follow-up.

Conclusion: Our study suggests the potential of the mLab App as a valuable tool for long-term HIV education and awareness for YMSM and YTGW. Further research is needed to understand the factors influencing the short-term effect on HIV knowledge. The mLab App may be a useful intervention for improving HIV knowledge.

Introduction: Adolescent girls and young women (AGYW) in Kenya have low pre-exposure prophylaxis (PrEP) initiation rates in part due to stigmatizing interactions with health care providers. Our recent randomized clinical trial of a standardized patient actor (SP) training intervention for providers found higher quality PrEP delivery at intervention sites, however it was unclear whether improved service quality improved PrEP initiation.

Methods: This analysis used routine records from facilities participating in the randomized trial which aimed to improve provider communication and adherence to Kenyan guidelines when offering PrEP to AGYW. We utilized facility-level PrEP registers from May-December 2019 as the baseline period and December 2020-June 2021 as the post-intervention period. We used linear regression with percent initiating as the outcome, intervention and baseline initiation levels as covariates, and the number eligible post-intervention at each facility as frequency weights.

Results: Overall, 1,375 AGYW presented to study sites, were eligible for PrEP, and were included in analyses (baseline: n=706, post-intervention: n=669). Among 669 PrEP-eligible AGYW in the post-intervention period (intervention: n=360, control: n=309), 591 (88.3%) initiated PrEP (intervention: n=335, control: n=256). PrEP initiation was 93.1% at intervention sites (range: 0%-100%) and 82.8% at control sites (range: 0%-100%). Adjusted for baseline initiation rates, initiation was 12.1% higher at intervention sites compared to control sites (p<0.001, [95% CI: 0.09, 0.15]).

Conclusions: Our study found significant improvement in PrEP initiation among AGYW who presented to intervention facilities. SP training interventions that improve quality of service delivery for AGYW could lead to higher population-level PrEP coverage.

Background: Latin America-amidst its largest mass migration-has seen minimal progress in curbing new HIV infections. Transgender women (TW) in the region are disproportionately affected, but scant data examines HIV vulnerabilities alongside migration.

Methods: Between February-July 2022, 211 young TW ages 16-24 in Lima participated in a cross-sectional quantitative study accompanied by serological testing (HIV, syphilis, chlamydia, gonorrhea, hepatitis B). Bivariate tests compared HIV and STI prevalence and related vulnerabilities among migrants to non-migrants. Poisson regression modeling estimated the association between time in Lima (non-migrant, 0-1 years, 2-5 years, ≥6 years) and HIV vulnerabilities (condom use).

Findings: Of 204 young TW, 110 were migrants to Lima (54%); 45% arrived in Lima ≤5 years ago. Most migrants were Peruvian (70% from Jungle regions); 14% were from Venezuela. HIV prevalence was 44% among migrants and 39% among non-migrants (p=0.67). Compared to non-migrants, migrants had higher prevalence of lifetime syphilis (65% vs 41%; p<0.01) and poor healthcare access (29% vs 12% no medical insurance), lifetime sex work (78% vs 55%; p<0.01) and sex work in past 30-days, (42% vs 8%; p<0.01), and client violence (23% vs 6%; p<0.01). Migrants arriving in Lima 0-1 years ago were more likely to report past 6-month condomless anal sex compared to non-migrants (adjusted prevalence ratio=1.54; 95% confidence interval=1.02-2.32).

Conclusion: Young TW face high rates of HIV and STIs, with vulnerabilities persisting even after resettlement for migrants. There is an urgent need for expanded HIV prevention and care for these women, and sustained health and social services for migrants in urban centers post-migration.

Background: We assessed clinical outcomes among children, adolescents, and people younger than 25 years on darunavir-based antiretroviral therapy (ART) in 9 sub-Saharan African countries.

Setting: Third-line ART centers in Cameroon, Eswatini, Kenya, Lesotho, Nigeria, Rwanda, Uganda, Zambia, and Zimbabwe.

Methods: From January 2019 to December 2022, we collected data from a cohort of children, adolescents, and young people receiving third-line ART from 9 sub-Saharan African countries. Data on treatment continuity, viral suppression, death, and clinic transfers were extracted from medical records and summarized. Cox proportional hazards models were used to identify factors independently associated with retention in care.

Results: Of 871 participants enrolled, the median age was 14.8 (range: 0.2-24.7) years and 488 (56.0%) were male; 809 (92.9%) [median duration of follow-up of 28.3 months (interquartile range: 17.5-45.2)] had final outcomes after initiating third-line ART. Of these, 711 (87.9%) were alive and in care at the end of study follow-up, 29 (3.6%) died, 30 (3.7%) were transferred to other facilities, and 39 (4.8%) were lost to follow-up. Retention in care was less likely among male patients compared with female patients [aHR: 0.85, 95% confidence interval: 0.72 to 1.0] and in 10-14-year-old children compared with younger children. Adolescents (15-19 years old) had higher mortality compared with children younger than 10 years (aSHR: 4.20, 95% confidence interval: 1.37 to 12.87). Viral suppression was seen in 345/433 (79.7%), 249/320 (77.8%), and 546/674 (81.0%) patients with results at 6 months, 12 months, and study end, respectively.

Conclusions: A high proportion of children and young people receiving third-line ART in sub-Saharan Africa remain in care and attain viral suppression during follow-up.