JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Tenofovir disoproxil fumarate (TDF) when used as preexposure prophylaxis (PrEP) in pregnancy is considered safe overall however there is insufficient evidence of its effect on maternal bone. We compared bone mineral density (BMD) and content (BMC) at the lumbar spine (LS) and hip of African breastfeeding women exposed and not exposed to TDF-containing PrEP in a randomized control trial (RCT).

Methods: This is a secondary data analysis of an RCT where pregnant women were randomized to initiating PrEP in pregnancy or delayed initiation of PrEP until breastfeeding cessation. BMD and BMC at the LS and hip were measured using dual-energy x-ray absorptiometry (DXA) at 6, 26, 50, and 74 weeks postpartum. In an exploratory analysis, BMD at the hip and LS were evaluated against varying Tenofovir (TFV) levels during pregnancy.

Results: Of 300 women in the RCT who had a DXA at 6 weeks postpartum, 102 (66%) women in the Immediate PrEP arm and 105 (72%) in the Delayed PrEP arm had a 74-week DXA scan. Adjusting for breastfeeding duration and body mass index (BMI), there were no significant differences in BMD or BMC at the hip and LS between treatment arms. There was no consistent dose-effect of TFV-DP detected during pregnancy on BMD at the hip (p=0.231) or the LS (p=0.277).

Conclusion: After adjusting for breastfeeding and BMI, TDF when given as oral preexposure prophylaxis during pregnancy had no deleterious effect on BMD and BMC at the hip and LS of African breastfeeding women.

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 people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs.

Methods: Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade.

Results: Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049].

Conclusions: In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended.

Background: There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV.

Methods: A retrospective cohort study was conducted among adult people with HIV (PWH) receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows one year prior to switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections.

Results: Included were 287 PWH with a median follow up time (IQR) of 450 days (344-548 days). Younger age [HR 0.97 (95%CI 0.95-0.98)] and ≥ 1 office visit no-show in the year prior to switch to LAI CAB/RPV [HR 2.03 (1.32-3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26-66.9)] with a trend towards younger age [HR 0.98 (0.95-1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n=3) after switch to LAI CAB/RPV.

Conclusions: Having office visit no-shows prior to switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.

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.

Background: Patient-reported outcome measures (PROMs) can provide data on the barriers and facilitators of adherence to daily oral antiretroviral therapy (OART) regimens. We aimed to develop PROMs to understand the perspectives of people with HIV (PWH) on (1) facilitators/barriers to daily OART regimen adherence and (2) a hypothetical switch to a long-acting (LA)-OART regimen.

Methods: Following the US food and drug administration patient-reported outcome guidance, targeted literature reviews and concept elicitation interviews with clinicians (n = 7) and PWH (n = 28) were conducted to develop conceptual models (CMs) of facilitators/barriers to OART regimen adherence. Three de novo PROMs were developed after an item-generation meeting. Three waves of cognitive debriefing interviews were conducted among PWH (n = 30) to demonstrate content validity and refine the PROMs.

Results: The targeted literature review identified 25 facilitators/barriers; an additional 16 facilitators/barriers were added by clinicians and PWH and represented in 2 CMs. During the item-generation meeting, the CMs were used to develop 3 de novo PROMs: (1) HIV Patient Perspective of Regimen, (2) HIV Patient Perspective of Regimen Change, and (3) HIV Drivers of Adherence Questionnaire. In the cognitive debriefing interviews, PWH corroborated the relevancy of items in the PROMs, and minor adjustments were made for clarity.

Conclusion: Three content-valid PROMs were developed to understand the treatment experience of PWH taking daily OART and how that experience may be altered upon a switch to weekly LA-OART. Data from future LA-OART clinical trials will help define a scoring guide and evaluate the structure and measurement properties of the PROMs.

Background: The World Health Organization is committed to strengthening access to pre-exposure prophylaxis (PrEP) for HIV prevention and its integration into primary care services. Unfortunately, the COVID-19 pandemic has disrupted the delivery of primary care, including HIV-related services. To determine the extent of this disruption, we conducted a systematic review and meta-analysis of the changes in access to PrEP services during the pandemic and the reasons for these changes.

Methods: A search was conducted using PubMed, Scopus, Embase, PsycINFO, and Cinahl for studies published between January 2020 and January 2023. Selected articles described self-reported disruptions to PrEP service access associated with the COVID-19 pandemic or its responses. Pooled effect sizes were computed using a random-effects model.

Results: Thirteen studies involving 12,652 PrEP users were included in our analysis. The proportion of participants reporting a disruption in access to PrEP services during the COVID-19 pandemic ranged from 3% to 56%, with a pooled proportion of 21% (95% confidence intervals: 8% to 38%). Social restrictions, financial constraints, and limited health insurance coverage were key factors affecting access to PrEP services during the pandemic.

Conclusions: To our knowledge, this is the first meta-analysis to quantify the extent of disruptions to accessing PrEP services because of the COVID-19 pandemic. To increase the ability of primary care services to maintain PrEP services during public health crises, a mixture of strategies is worth considering. These include multi-month PrEP prescriptions, telehealth services, deployment of peer support groups to provide a community-based service or home delivery, and provision of financial support interventions.

Background: South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition.

Setting: South African public sector.

Methods: We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine rings as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation -Adolopment process. We appraised the systematic review and randomized controlled trial (RCT) evidence underpinning the selected guideline's recommendations and conducted a cost-effectiveness analysis. The Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework guided the adaptation of source guideline recommendations, according to our local context.

Results: We identified the 2021 World Health Organization PrEP Guidelines, informed by 2 placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring vs placebo (95% confidence interval: 10 to 34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP or among adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price.

Conclusions: The source guideline recommendation was adapted for the local context. Dapivirine ring seems to be less efficacious than oral PrEP, although comparative studies are lacking. Data on adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List.

Introduction: In Africa, migrants are more likely to be living with HIV and HIV viremic than non-migrants but less is known about HIV outcomes among non-migrants living in households with migrants. We compared HIV outcomes in non-migrating persons in households with and without migration.

Methods: We analyzed cross-sectional data collected between August 2016-May 2018 from non-migrating participants aged 15-49 in the Rakai Community Cohort Study in Uganda. Migrant households were classified as those reporting ≥1 member moving into or out of the household since the prior survey. HIV serostatus was determined using a validated testing algorithm, and viremia defined as >1,000 copies/mL. Modified Poisson regression was used to estimate prevalence ratios (PR) between household migration and HIV outcomes. Analyses were stratified by gender, direction of migration (into/out of household), and relationship between non-migrants and migrants (e.g., spouse).

Results: There were 14,599 non-migrants (52% women) and 4,415 (30%) lived in a household with ≥1 migrant. Of these, 972 (22%) had migrant spouses, 1,102 (25%) migrant children, and 875 (20%) migrant siblings. Overall, HIV prevalence and viremia did not differ between non-migrants in households with and without migration. However, in stratified analyses, non-migrant women with migrant spouses were significantly more likely to be HIV seropositive compared to non-migrant women with non-migrant spouses (adjPR:1.44, 95%CI:1.21-1.71). Conversely, non-migrant mothers living with HIV who had migrant children were less likely to be viremic (adjPR:0.34, 95%CI:0.13-0.86).

Conclusions: Non-migrating women with migrating spouses are more likely be living with HIV, and may benefit from additional HIV support services.