JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: In 2017, Blantyre district had the highest adult HIV prevalence in Malawi (17.7%) and lowest viral suppression (60%). In response, the Ministry of Health expanded prevention and treatment services. We assessed whether outreach to social venues could identify individuals with increased HIV acquisition risk or with unsuppressed HIV not currently reached by clinic-based services.

Methods: We conducted a cross-sectional biobehavioral survey in Blantyre, Malawi, from January to March 2022. We visited social venues where people meet new sexual partners and government clinics providing HIV testing or STI screening. Participants older than 15 years were interviewed and tested for HIV infection if not on ART. HIV recency tests were performed on those testing positive, and dried blood spots (DBS) were collected to quantify viral load and also to identify acute infection in those with HIV- results.

Results: HIV prevalence (18.5% vs 8.3%) and unsuppressed HIV infection (3.9% vs 1.7%) were higher among venue-recruited (n = 1802) than among clinic-recruited participants (n = 2313). Among PLHIV at both clinics (n = 199) and venues (n = 289), 79% were virally suppressed. Few had acute (n = 1) or recent infection (n = 8). Among women, HIV prevalence was 4 times higher (38.9% venue vs 8.9% clinic). At clinics, PLHIV reporting visiting venues were less likely to be suppressed (54.6 vs 82.6%). More men at venues than at clinics reported paying for sex (49% vs 30%) or having multiple sex partners in the past 4 weeks (32% vs 16%).

Conclusions: Enhanced venue-based prevention and testing for men and women could reduce treatment lapses, onward transmission, and improve HIV treatment outcomes.

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 behaviorally 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 from August 2022 to November 2022.

Methods: A quasi-experimental study was conducted to evaluate 4 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 center. 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 with 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 with SOC form. Users submitting the foot-in-the-door form were less likely to be booked/referred compared with those using the SOC form (-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 behavioral 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.

Introduction: Kaposi sarcoma (KS) is an angioproliferative disease caused by human herpesvirus 8 and is mediated by cytokines in an immunodeficient environment. This study aimed to compare IL-6, IL-10, and TNFα levels among patients with AIDS with disseminated KS (DKS), treatment naïve patients living with HIV without DKS, and healthy controls. Secondary outcomes were to compare cytokines levels in patients with DKS and unfavorable outcomes, and an analysis of the behavior of cytokines over time.

Methods: This cohort study was performed at 2 centers in Mexico City. Three groups were included. Group 1: HIV+ treatment naïve with DKS, group 2: HIV+ treatment naïve without KS, and group 3: HIV negative, healthy controls. Plasmatic IL-6, IL-10, and TNFα levels were measured at baseline and over time in groups 1 and 2.

Results: Seventy-six patients were included: 39 (52%) in group 1, 17 (22%) in group 2, and 20 (26%) in group 3. The median baseline IL-6, IL-10, and TNFα levels were significantly higher in group 1. In group 1, baseline IL-6 was higher in patients who died than in survivors (14.4 vs 5.8 pg/mL P = 0.048). Patients with severe immune reconstitution inflammatory syndrome because of KS had higher IL-6 values than those without it (14.4 vs 5.8 pg/mL P = 0.004). In the repeated measures model in group 1, IL-10 levels were higher in patients who died ( P < 0.001) and developed immune reconstitution inflammatory syndrome-KS ( P = 0.01).

Conclusions: IL-6, IL-10, and TNF α levels were markedly higher in patients with DKS. IL-6 and IL-10 levels were higher in patients with unfavorable outcomes.

Background: The Visitect CD4 Advanced Disease test (AccuBio, Alva, United Kingdom) is a rapid, semiquantitative assay that estimates CD4 results above or below 200 cells per microliter. We evaluated the performance of the Visitect CD4 assay in semiurban laboratories in Uganda.

Methods: We performed a pragmatic laboratory validation of the Visitect CD4 platform in 4 routine HIV clinics in Uganda, nested within a cluster randomized trial evaluating an enhanced package of screening and treatment for persons with advanced HIV disease (NCT05085171). As part of the clinical trial, samples processed on the Visitect CD4 platform were confirmed using another CD4 testing method. We compared the diagnostic performance of the Visitect CD4 platform against the confirmatory method by evaluating the sensitivity, specificity, and positive and negative predictive values.

Results: Of 1495 venous blood samples that were processed both by the Visitect CD4 test and another confirmatory CD4 platform at clinics in Kampala, Uganda, specificity was 81% [95% confidence interval (CI): 79% to 84%] and the positive predictive value was 69% (95% CI: 66% to 73%). There were no samples for which the Visitect test was >200 cells per microliter and the confirmatory test was ≤200 cells per microliter, resulting in a sensitivity of 100%. Among Visitect CD4 tests that were read as ≤200 cells per microliter with confirmatory results >200 cells per microliter, the median confirmatory CD4 result was 397 (IQR, 281-590) cells per microliter. Specificity varied by clinic ranging from 63% to 99%.

Conclusions: Given variable specificity of the Visitect CD4 Advanced Disease platform, successful implementation will require consideration of clinic context and laboratory staffing.

Background: The relationship between HIV and frailty, a predictor of poor outcomes in the face of stressors, remains unknown in older people in sub-Saharan Africa.

Methods: We analyzed data from the Quality of Life and Ageing with HIV in Rural Uganda cohort study to estimate the prevalence and correlates of frailty among older people with HIV (PWH) on long-term antiretroviral therapy and among age- and sex-matched HIV-uninfected comparators. Frailty was defined as a self-report of 3 or 4 (and pre-frailty as 1 or 2) of the following phenotypic variables: weight loss, exhaustion, low activity, and slowness. We estimated the prevalence of frailty and prefrailty and fitted logistic regression models to estimate the association between HIV and frailty, adjusting for sociodemographic factors, depression, and other comorbidities.

Results: We enrolled 599 participants (49% women) with a mean age of 58 years. PWH had a similar prevalence of frailty (8.1% vs. 10.9%, P = 0.24) but a lower prevalence of prefrailty (54.2% vs. 63.2%, P = 0.03) compared with their HIV-uninfected comparators. In multivariable regression models, people with depression [adjusted odds ratio (AOR) 7.52 (95% CI: 3.67 to 15.40), P < 0.001] and those with ≥1 comorbidities [AOR 3.15 (95% CI: 1.71 to 3.82), P < 0.001] were more likely to be frail. HIV serostatus was not significantly associated with frailty [AOR 0.71 (95% CI: 0.37 to 1.34), P = 0.29].

Conclusions: Older PWH had a similar prevalence of frailty as those without HIV. These findings call for additional study of the factors that contribute to the robustness of older PWH in sub-Saharan Africa.

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

Methods: Age- and sex-matched PLWH with and without obesity (body mass index ≥30 kg/m 2 ) from a multicenter, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (high sensitivity C-Reactive Protein [hsCRP], interleukin (IL)-2, IL-6, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, tumor necrosis factor-alpha, interferon-gamma, IL-18), coagulation (von Willebrand Factor [vWF], D-dimer, soluble CD40 ligand), endothelial function (E-selectin, P-selectin, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1), atherosclerosis (myeloperoxidase [MPO], lipoprotein-associated phospholipase A2), immune regulation (IL-1 receptor antagonist [IL-1RA]), innate immune activation (macrophage inflammatory protein-1, monocyte chemoattractant protein-1, soluble CD163, soluble CD14), and microbial translocation (lipopolysaccharide binding protein) were measured in the 2 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, sex, ethnicity, smoking status, and antiretroviral therapy.

Results: Ninety-nine antiretroviral therapy-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 lipopolysaccharide binding protein. 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 (adjusted odds ratio 2.7, 95% CI: [1.7 to 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]), and 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 toward an unfavorable 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 in the United States 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 (HCP); 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 4 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 weekly pill, yearly implant, 6-monthly HCP injection, oral daily pill, and 3-monthly HCP injections were 24%, 24%, 24%, 18%, and 11%, respectively.

Conclusions: Patterns of HIV medication preference can inform development of new forms of HIV therapy products because 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 people with HIV increases the ability to develop patient-centered products to fill gaps in care and increase treatment effectiveness.

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 January 01, 2007, and December 31, 2016, were categorized using World Health Organization criteria into mild (11.0-12.9 g/dL men, 11.0-11.9 g/dL women), moderate (8.0-10.9 g/dL men/women), and severe (<8.0 g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazard 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 men (adjusted hazard ratios = 5.8 [5.4, 6.2]) versus women (adjusted hazard ratios = 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 decreased significantly in the 4 years before death, with a maximum decrease in the year before death. Macrocytic anemia was associated with an increased mortality risk and microcytic anemia was associated with 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 association and microcytic anemia having a decreased association with mortality compared with normocytic anemia.

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: 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.