JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, although false (both negative and positive) results are expected to occur.

Setting: We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using 3 contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia.

Methods: HIV serologic testing was conducted quarterly using 2 parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and RNA.

Results: A total of 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (ie, 1 negative and 1 positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing, but 6 (9.7%) had dually positive rapid results, and 4 (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%.

Conclusions: Although most rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.

Trial registration: ClinicalTrials.gov number NCT02550067.

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

Methods: HIV-uninfected adults received a series of 3 rectal PC-1005 doses-4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours.

Results: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity.

Conclusions: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate.

Clinical trials: NCT03408899.

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: 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.

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: Following the conclusion of a stepped-wedge cluster randomized trial of the Systems Analysis and Improvement Approach (SAIA) to optimize the prevention of mother-to-child HIV transmission cascade in Manica Province, Mozambique, we conducted a natural experiment to test the sustainability of the delivery model with limited financial inputs.

Methods: District nurse supervisors were encouraged to continue to facilitate SAIA cycles in subordinate health facilities and provided phone credit and tablet access to upload implementation data. No additional resources (eg, funds for transport, refreshments, or supplies) were provided. Barriers to implementation were collected via conversations with district supervisors.

Results: Monthly facilitation of SAIA cycles continued in 11 of 12 (92%) districts and 13 of 36 (36%) facilities through 12 months posttrial, which declined to 10 districts and 10 facilities by the end of the 15-month posttrial period. Despite interest among district supervisors to continue implementation, logistical and financial barriers prevented visits to facilities not in close proximity to district management offices. Turnover of district supervisors resulted in replacements not having knowledge and experience facilitating SAIA. The lack of refreshments for facility staff and limited supplies (pens and papers) were cited as additional barriers.

Conclusion: Despite the scalability of the SAIA model, it is susceptible to implementation decay without sufficient health system resources. Additional research is needed to test sustainment strategies that address identified barriers and enable continued delivery of the implementation strategy core components at a sufficient level of fidelity to maintain desired health system improvements and patient-level outcomes.

Abstract: We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tablet-based neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4 + and CD8 + ) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13-16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV ( P = 0.05) and significantly worse on tests of executive functioning and delayed recall ( P 's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P = 0.04), attention, processing speed, and motor speed (r = 0.2-0.3, P ≤ 0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r = 0.2-0.4, P ≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI: -0.55 to -0.07, P = 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting.

Introduction: People with HIV (PWH) have nearly twice the risk of emphysema than people without HIV. This risk, which has been associated with HIV-mediated changes in the lung immune environment and more extensive radiographic emphysema, may result in different patterns of airflow limitation on pulmonary function testing (PFT) than those traditionally used in people without HIV.

Methods: In this prospective cohort of PWH in Atlanta, Georgia, we analyzed PFT and chest computed tomography data from July 2013 through June 2018. After comparing the prevalence of PFT measures of airflow limitation for those with and without radiographic emphysema, we used binary recursive partitioning to identify PFT measures that differentiated between PWH with and without radiographic emphysema.

Results: Among 167 PWH who had both PFT and computed tomography data during the study period, 89 (53%) had radiographic emphysema. Those with radiographic emphysema were more likely to have airflow limitations on PFTs. Recursive partitioning identified partitions at a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of 0.78 and a residual volume of 116% predicted. These partitions enabled the identification of 84 (94%) PWH with radiographic emphysema, in contrast to the traditional diagnostic criteria of an FEV1/FVC ratio of 0.7, which only identified 49 (55%) of those with radiographic emphysema.

Conclusions: Emphysema in PWH may have different patterns of airflow limitation on PFTs that are not adequately captured by traditional diagnostic criteria. Future studies can seek to validate these findings and determine optimal thresholds for diagnosing HIV-associated emphysema.

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.