JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity.

Methods: Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, gender, ethnicity, smoking status, and antiretroviral therapy (ART).

Results: Ninety-nine ART-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and LBP. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation and atherosclerosis pathways were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (aOR 2.7, 95% CI [1.7, 4.29]), IL-6 (3.77 [1.43, 9.93]), vWF (5.33 [1.51, 18.75]), E-selectin (6.28 [1.36, 29.04]), MPO (6.85 [1.87, 25.04]), IL-1RA (6.45 [2.28, 18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation.

Conclusions: Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Background: New dosage form and frequency options may improve HIV treatment outcomes and reduce disparities in access and use.

Methods: People with HIV (PWH) in the US completed a demographic and discrete choice experiment survey of preference for 13 hypothetical HIV treatment options: daily and weekly oral tablets; 1-, 3-, or 6-monthly injections by self or a health care provider; yearly implant; or combinations. Best-worst scaling and a latent class model were used to analyze overall preference choices and for groups of individuals with similar patterns of preferences; the model also predicted uptake of products.

Results: Among the diverse 829 respondents, weekly oral tablets and 6-monthly injections by an HCP were significantly more favored than daily oral tablets. Convenience of the treatment and being tired of taking pills were the top drivers of preference responses. Latent class analysis identified four groups of respondents with distinct preference patterns; approximately two-thirds belonged to groups strongly preferring products other than daily oral tablets. The modelled uptake of a monthly pill, yearly implant, 6-monthly Health Care Provider (HCP) injection, oral daily pill, and 3-monthly HCP injection were 24%, 24%, 24%, 18%, and 11%, respectively.

Conclusions: Patterns of HIV medication preference can inform development of new forms of HIV therapy products as the majority of patients do not prefer the currently most available treatment option of daily oral tablets. Looking beyond population-level preferences and into similar groups of PWH increases the ability to develop patient-centered products to fill gaps in care and increase treatment effectiveness.

Background: While voluntary medical male circumcision (VMMC) reduces the risk of HIV transmission by 60%, circumcision coverage falls short of the UNAIDS 90% VMMC target. We investigated whether behaviourally informed message framing increased demand for VMMC.

Setting: Adult users of the MoyaApp, a data free application in South Africa, who viewed a form designed to generate interest in VMMC during August-November 2022.

Methods: A quasi-experimental study was conducted to evaluate four MoyaApp VMMC intervention forms against the Standard of Care (SOC) form. All forms enabled users to provide contact details for follow-up engagement by a call centre. The primary outcome was the proportion of forms submitted. Secondary outcomes included successful contact with the user, VMMC bookings/referrals and confirmed circumcision. Multivariable ordinary least-squares regression was used for the analysis.

Results: Of 118,337 MoyaApp VMMC form viewers, 6% submitted a form. Foot-in-the-Door form viewers were more likely (+1.3 percentage points, p<0.01) to submit a form compared to the SOC group (6.3%). Active Choice (-1.1 percentage points, p<0.01) and Reserved for You (-0.05 percentage points, p<0.05) form viewers were less likely to submit a form compared to SOC. Users submitting on Foot-in-the-Door were less likely to be booked/referred compared to SOC (-5 percentage points, p<0.05). There were no differences between the intervention and SOC forms for successful contact and circumcisions.

Conclusions: Message framing using behavioural insights was able to nudge men to engage with VMMC services. However, more work is needed to understand how to convert initial interest into bookings and circumcisions.

Background: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America.

Methods: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality.

Results: Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia).

Conclusions: Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.

Background: Outside of randomized controlled trials (RCTs), there are limited data regarding the acceptability of injectable long-acting cabotegravir + rilpivirine (LA-CAB+RPV) among persons living with HIV (PLWH). To evaluate acceptability, we describe participant-reported outcomes (PRO) of LA-CAB+RPV among a population underrepresented in RCTs.

Setting: Ruth M. Rothstein Core Center (CORE), large urban HIV clinic in Chicago, Illinois, USA.

Methods: We interviewed PLWH prescribed LA-CAB+RPV who receive primary care at CORE. PRO endpoints included treatment satisfaction, tolerability of injections, reasons for switching to LA-CAB+RPV, and unexpected effects of LA-CAB+RPV. Mean and standard deviations (mean±SD) and proportions (%) are reported.

Results: Among respondents (N=150), 67% identified as Non-Hispanic Black, 24% Hispanic, 56% male; the average age was 43 years (SD:13.2), and 37% were ≥50 years old. Most respondents (93%) completed ≥3 injection appointments at the time of interview. The most common reasons for switching to LA-CAB+RPV were no longer wanting to take pills (89%) and trouble taking their pills daily (58%). Treatment satisfaction was high (6.7±0.5 out of 7). Two-thirds (61%) reported an unexpected aspect of their life improved. Pain from injections was common (98%), with a mean pain score of 4.3 out of 10. Among those reporting pain, half (47%) reported pain decreased after initial injection. Among participants reporting pain score >6 (n=36), most (78%) reported no improvement since initial injection.

Conclusions: We found high treatment satisfaction with LA-CAB+RPV in a diverse population. Participants reported moderate injection pain, which improved with time. Results suggest injectable LA-CAB+RPV will be met with acceptability across diverse participant populations.

Background: Associations of sleep deficiency and methamphetamine use with sexual health and HIV treatment outcomes are poorly understood.

Setting: A longitudinal cohort of men who have sex with men at risk for or living with HIV (the mSTUDY) was analyzed. This analysis included 1445 study visits among 382 participants. Data were collected from June 2018 to February 2022.

Methods: Semiannual study visits included self-interviews for sleep deficiency, sexual behaviors, substance use, and HIV treatment. Sleep deficiency was measured using the Pittsburgh Sleep Quality Index. Participants provided specimens for HIV viral load and sexually transmitted infection (STI) testing (chlamydia, gonorrhea, syphilis). Associations between sleep deficiency and STI/HIV outcomes were estimated using multiple logistic regression.

Results: Across visits, the prevalence of sleep deficiency was 56%, with 33% reporting methamphetamine use and 55% living with HIV. Sleep deficiency was associated with reporting at least 1 new anal sex partner (aOR = 1.62, 95% CI: 1.21 to 2.15), exchange sex (aOR = 2.71, 95% CI: 1.15 to 6.39), sex party attendance (aOR = 2.60, 95% CI: 1.68 to 4.04), and missing HIV medications (aOR = 1.91, 95% CI: 1.16 to 3.14). The association between sleep deficiency and exchange sex differed for participants who did and did not report the use of methamphetamine (P = 0.09).

Conclusion: Sleep deficiency was associated with sexual health and HIV treatment behaviors after accounting for methamphetamine use. Sleep health should be considered in STI/HIV prevention, particularly for those who use methamphetamine.

Background: HIV testing rates among South African men lag behind rates for women and national targets. Community-based HIV self-screening (HIVSS) distribution and follow-up by community health workers (CHWs) is a scalable option to increase testing coverage, diagnosis, and treatment initiation. We provided HIVSS and assisted linkage to care to men not recently tested (within the past 12 months) residing in high-HIV-burden areas of Johannesburg.

Methods: CHWs distributed HIVSS in 6 clinic catchment areas. Follow-up to encourage confirmatory testing and antiretroviral therapy initiation was conducted through personal support (PS) or an automated short message service (SMS) follow-up and linkage system in 3 clinic areas each. Using a quasi-experimental pre-post design, we compared differences in the proportion of men testing in the clinic catchment areas during the HIVSS campaign (June-August 2019) to the 3 months prior (March-May 2019) and compared treatment initiations by assisted linkage strategy.

Results: Among 4793 participants accepting HIVSS, 62% had never tested. Among 3993 participants with follow-up data, 90.6% reported using their HIVSS kit. Testing coverage among men increased by 156%, from under 4% when only clinic-based HIV testing services were available to 9.5% when HIVSS and HIV testing services were available (z = -11.6; P < 0.01). Reported test use was higher for men followed through PS (99% vs. 68% in SMS); however, significantly more men reported reactive self-test results in the SMS group compared with PS (6.4% vs. 2.0%), resulting in more antiretroviral therapy initiations in the SMS group compared with PS (23 vs. 9; P < 0.01).

Conclusions: CHW HIVSS distribution significantly increases testing among men. While PS enabled personalized follow-up, reporting differences indicate SMS is more acceptable and better aligned with expectations of privacy associated with HIVSS.

Introduction: VESTED (NCT03048422) compared the safety and efficacy of three antiretroviral treatment (ART) regimens in pregnant and postpartum women: dolutegravir+emtricitabine/tenofovir alafenamide fumarate; dolutegravir+emtricitabine/tenofovir disoproxil fumarate (TDF); efavirenz/emtricitabine/TDF. Vertical HIV transmission (VT) occurred to 4/617 (0.60%) live-born infants, who were evaluated for HIV drug resistance (HIVDR) and other risk factors.

Setting: In 2018-2020, pregnant (weeks-14-28) women living with HIV and ≤14 days of ART were enrolled at 22 international sites and followed with their infants through 50 weeks postpartum.

Methods: HIV sequences derived by single genome amplification (SGA) from longitudinally collected specimens were assessed from VT Cases for HIVDR in protease, reverse transcriptase, integrase, and the nef 3'polypurine tract (3'PPT).

Results: The four Case mothers were prescribed efavirenz-based-ART for 1-7 days prior to randomization to study ART. Their infants received postnatal nevirapine+/-zidovudine prophylaxis and were breastfed. A total of 833 SGA sequences were derived. The "major" (Stanford HIVDR Score ≥60) non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation (K103N) was detected persistently in one viremic mother, and likely contributed to VT of HIVDR. Major NNRTI HIVDR mutations were detected in all three surviving infants. No integrase, nor high frequencies of 3'PPT mutations conferring dolutegravir HIVDR were detected. The timing of HIV infant diagnosis, plasma HIV RNA levels and HIVDR suggests one in utero, one peripartum, one early, and one late breastfeeding transmission.

Conclusions: VT was rare. New-onset NNRTI HIVDR in Case mothers was likely from efavirenz-ART prescribed prior to study dolutegravir-ART, and in one case appeared transmitted to the infant despite nevirapine prophylaxis.

Background: Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, though 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 three contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia.

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

Results: 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 (i.e., one negative and one 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 six (9.7%) had dually-positive rapid results and four (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%.

Conclusion: Although the majority of 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.