JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Effective implementation of evidence-based HIV prevention interventions continues to be a challenge in the United States, and the field is increasingly turning to implementation science for solutions. As such, it is critical to expand the current implementation science vocabulary-and its taxonomy of implementation strategies-to increase its relevance and utility for front-line implementers.

Setting: Community-based health centers providing HIV prevention services in the southeastern United States.

Methods: We conducted a collective case-study analysis, combining document review and qualitative interviews with program directors, clinicians, and other providers (N = 30) at 5 sites. We used an inductive and iterative analytic approach to specify and categorize strategies, and then conducted in-depth cross-case analysis to derive a practice-driven taxonomy of HIV prevention implementation strategies.

Results: From an initial matrix of 264 activities, we identified 50 strategies common across sites. In contrast to existing implementation science frameworks, most (68%, n = 34) strategies were designed to affect implementation outcomes (eg, acceptability, adoption, feasibility) for patients. We present a practice-driven taxonomy of these strategies, operationalized according to implementation science literature, but with terminology that more directly relates to implementers.

Conclusions: Findings demonstrate the feasibility and utility of this method for developing a practice-driven implementation science vocabulary for HIV prevention. Our evidence-based taxonomy provides a framework for implementers seeking data about the universe of strategies they might consider for their own programs, and increases researchers' ability to measure and evaluate the effectiveness of implementation strategies being enacted in practice settings.

Background: Implementation science has been heralded as a critical strategy for ending the HIV epidemic, and the United States has made a tremendous financial investment in implementation research. However, several dynamics in its development and organization may alienate front-line implementers and recapitulate some of the same missteps that have stymied past translational work.

Setting: Increasing the accessibility and relevance of HIV implementation science for front-line implementers (eg, health department and health systems directors, clinic administrators, program managers, clinicians, and other providers) is critical.

Methods: We review current challenges to the meaningful inclusion of front-line implementers in implementation science research, and consider specific changes to language, frameworks, and methods that would maximize the accessibility and relevance of the field.

Results: Our analysis suggests the need for greater attention to implementation strategies most relevant to front-line implementers, that is, those focused on intervention recipients. We propose a novel, multilayer framework for conceptualizing the strategies necessary to achieve HIV implementation outcomes by organizations, providers, and recipients. There is a compelling rationale to adopt incentive structures that prioritize research questions most important for practice.

Conclusions: Maximizing the impact of implementation science on ending the HIV epidemic goals requires (1) expanding the focus of implementation science to include more recipient-focused implementation strategies, (2) developing and applying frameworks that better reflect the experience and needs of front-line implementers, (3) using language most relevant and applicable to practice, and (4) prioritizing actionable research questions that directly address the needs and concerns of those doing implementation work.

Introduction: Couple-based behavioral interventions (CBIs) have been associated with improved HIV virological outcomes for pregnant women and their male partners living with HIV in observational settings, but have never been tested in a randomized controlled trial (RCT).

Setting: Bwaila District Hospital Antenatal Clinic (Lilongwe, Malawi).

Methods: An RCT was conducted among 500 pregnant women living with HIV (index clients) randomized 1:1 to the standard of care (SOC) or CBI and followed for 1 year. The CBI offered an initial session for index clients, HIV-assisted partner notification, 2 enhanced couple counseling and testing sessions, illustrated materials, and antiretroviral therapy pickup for either couple member at the antenatal clinic. At 12 months, viral load among index clients and male partners with HIV was measured. Risk differences (RD) and 95% confidence intervals (CIs) compared viral suppression (<1000 copies/mL) between arms.

Results: The mean index client age was 26.6 years; most were married or cohabiting (93.3%). Index client viral suppression was 6.5% higher in the CBI arm (88.0%) than in the SOC arm (81.6%). Male partner viral suppression was 16.2% higher in the CBI arm (73.6%) than the SOC arm (57.4%). Overall, couple viral suppression was 7.8% higher (CI: 0.5% to 15.1%, P = 0.04) in the CBI arm (84%) than in the SOC arm (76.0%). Social harms were rare (3.6%) and comparable between arms ( P = 0.8).

Conclusions: This CBI had a positive impact on couple viral suppression. Scaling this CBI to antenatal clients with HIV and their male partners could improve HIV outcomes among expecting families.

Background: Modest weight and lipid changes have been observed in cabotegravir plus rilpivirine long-acting (CAB + RPV LA) phase 3/3b studies. The SOLAR study included standardized evaluations of weight and metabolic changes in people living with HIV switching to CAB + RPV LA dosed every 2 months (Q2M) vs. continuing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

Setting: Phase 3b, randomized, open-label study conducted in 118 centers across 14 countries.

Methods: Participants (n = 687) were randomized 2:1; 454 switched to CAB + RPV LA Q2M and 227 continued BIC/FTC/TAF. Participants who started lipid-modifying agents or underwent cosmetic procedures were excluded. We analyzed changes in body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), muscle mass, body fat, and proportion with insulin resistance or metabolic syndrome at 1 year.

Results: Median (interquartile range) change in body weight from baseline was -0.40 kg (-2.95 to +2.10) and +0.05 kg (-2.30 to +1.95) in the LA and BIC/FTC/TAF arm, respectively. Median (interquartile range) changes in WC and HC were +0.06 cm (-4.50 to 4.00) and +0.00 cm (-4.00 to 3.97) in the LA arm, and +1.14 cm (-3.00 to 5.09) and +0.13 cm (-3.10 to 4.00) in the BIC/FTC/TAF arm. There were no clinically relevant changes in WHtR, WHR, or the proportion with metabolic syndrome or insulin resistance in either arm.

Conclusions: Standardized changes in weight, BMI, and body composition were minor and similar between participant switching to CAB + RPV LA Q2M or continuing BIC/FTC/TAF, with no clinically relevant changes in metabolic syndrome or insulin resistance.

Background: Despite high oral pre-exposure prophylaxis (PrEP) uptake among young heterosexual cisgender women, early discontinuation is frequent. It is unclear whether this aligns with potential HIV exposure.

Methods: Young women aged 16-25 years and ≥1 of their male partners were enrolled in separate but linked longitudinal HIV PrEP studies in Kampala, Uganda, from 2018 to 2021. Data on sexual behavior, PrEP use, sexually transmitted disease positivity, and Y chromosome DNA (Yc DNA; a marker for condomless sex) were collected at enrollment and quarterly visits. Potential HIV exposure was defined as one of the following in the past 3 months: any sexually transmitted disease, detection of Yc DNA, condomless vaginal sex, or multiple sex partners. Alignment between potential HIV exposure and PrEP use by participants was examined using generalized estimating equation (GEE) regression.

Results: Eighty-eight young women (median age = 20.6 years, interquartile range 19.5-22.0) and 124 male partners (median age = 23.5 years, interquartile range 21.0-26.0) were included. Women and men were dispensed PrEP in 66.9% and 60.5% of their first linked visits, respectively. PrEP dispensation was more common when women or men self-reported condomless vaginal sex and multiple sex partners or when women had Yc DNA detected in vaginal swabs. Men's self-report of multiple partners (adjusted prevalence ratio = 1.56, P = 0.012) and the detection of Yc DNA (adjusted prevalence ratio = 1.52, P = 0.040) were significantly associated with women's PrEP dispensation.

Conclusions: Women and their male partners may align their PrEP use with their HIV risk behaviors, providing some reassurance that PrEP discontinuation in young people often aligns with sexual behavior. Greater attention to measurement of and mismatches in PrEP discontinuation and potential HIV exposure is needed.

Introduction: The US state of Florida has the third highest rate of HIV and 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 3 Ryan White HIV/AIDS Program (RWHAP)-funded clinics in Florida between August 2020 and 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 rescreening. About 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: The risk of onward HIV transmission is strongly influenced by the interval between HIV infection and its diagnosis. The SELPHI trial examined whether this interval could be reduced by offering free HIV self-testing kits to men who have sex with men (MSM).

Setting: Internet-based RCT of MSM aged ≥16 years, resident in England/Wales, recruited through sexual and social networking sites.

Methods: The second-stage randomization of SELPHI was open to participants who used an initial free HIV self-test kit, were HIV seronegative, and reported recent condomless anal sex. They were randomized to receive a free HIV self-test kit every 3 months (repeat testing [RT] group) versus no such offer (nRT group). The primary outcome was time from randomization to a confirmed HIV diagnosis, determined from linkage to national HIV surveillance databases. The key secondary outcome was the frequency of HIV testing regardless of test modality.

Results: In total, 2308 eligible participants (1161 RT, 1147 nRT) were randomized between April 2017 and June 2018, and followed for 15-27 months. The proportion of participants reporting an HIV test in the previous 3 months was much higher in the RT group (86%) than in the nRT group (39%). Overall, 16 (9 RT, 7 nRT) confirmed HIV diagnoses were observed (0.35/100 person-years), with no difference between the groups (hazard ratio = 1.27 [95% CI: 0.47 to 3.41], P = 0.63).

Conclusions: Providing regular free self-testing kits to sexually active MSM was highly acceptable and markedly increased HIV testing. However, in this low incidence cohort, it did not result in a demonstrably more rapid diagnosis of incident infections.

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 stigma reduction training for providers whose design was informed by direct observation of their clinical behaviors obtained through visits by incognito standardized patients (SPs).

Setting: We conducted this study in sexually transmitted disease 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 the impact using linear fixed effects regression.

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

Conclusions: Our training reduced stigma 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.

Background: The impact on infant bone, growth, and renal health of in utero and breastmilk exposure to contemporary antiretroviral treatment (ART) remains unclear.

Methods: 643 pregnant women with HIV in nine countries in Africa, Asia and the Americas were randomized to start ART with dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG + FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF between 14-28 weeks' gestation and continued for 50 weeks postpartum. Pairwise comparisons used two-sample t-tests of mean week 26 infant bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry (DXA) in a subset; mean infant z-scores for length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) at 26 and 50 weeks; and mean infant creatinine and estimated creatinine clearance at birth and 26 weeks.

Results: 577 infants were included in the growth analysis, and 169 in the DXA analysis. Week 26 infant spine BMC was significantly lower in the EFV/FTC/TDF arm (133.5g) compared to the DTG+FTC/TAF (143.4g; mean difference [95% CI]: 0.22 [0.02, 0.42] g) and DTG+FTC/TDF (137.4; mean difference [95%CI]: 0.20 [0.01, 0.40] g) arms. Mean LAZ and WAZ scores through week 50 were also significantly lower in the EFV/FTC/TDF versus DTG arms, but not WLZ. Infant obesity was rare (2-4%) and similar between arms. There was no apparent by-arm difference in infant creatinine or estimated creatinine clearance through week 50 (p-values ≥ 0.18).

Conclusion: It is reassuring that maternal DTG-based ART during pregnancy and breastfeeding was associated with higher infant spine bone mineral content, better growth, and less stunting than EFV/FTC/TDF.

Background: Raltegravir is an HIV integrase strand transfer inhibitor recommended for use in pregnancy. The aim of this study was to assess risk of birth defects and other suboptimal outcomes following prenatal exposure to raltegravir.

Methods: We used pooled, prospectively-collected individual patient data from studies in the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC). Pregnancies with any prenatal exposure to raltegravir with outcomes in 2008-2020 were included. Birth defects were classified according to World Health Organization's International Classification of Diseases: Tenth Revision (ICD-10) and EUROCAT criteria. Earliest prenatal exposure timing was classified as periconception (exposure at ≤6 completed gestational weeks [GWs]), later first trimester (T1) (exposure in T1 at >6 completed GWs), and second/third trimester (exposure at >12 completed GWs).

Results: A total of 1499 pregnancies across nine cohorts were included. Where timing was available (n=1449), earliest raltegravir exposure was in the periconception period for 505 (34.8%), later T1 in 65 (4.5%), and T2/T3 in 879 (60.7%). The overall prevalence of birth defects among live-born infants with prenatal raltegravir exposure was 3.9% (95% CI 2.9, 5.0) (1443/1466) (ICD-10), with no increased risk observed for those exposed in the periconception period (p=0.290). Among singleton live-born infants, 11.9% (160/1346) were born preterm, 11.3% (148/1307) low birthweight, and 8.6% (111/1291) small for gestational age, with no difference in outcomes observed by timing of raltegravir exposure.

Conclusion: These findings add to the evidence base around safety of raltegravir use in pregnancy, though ongoing safety monitoring is needed to rule out risk of rare outcomes.