JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

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 (BIC/FTC/TAF).

Setting: Phase 3b, randomized, open-label study conducted in 118 centres 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 analysed changes in body weight, body mass index (BMI), waist and hip circumferences (WC, 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, +2.10) and +0.05 kg (-2.30, +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, 4.00) and +0.00 cm (-4.00, 3.97) in the LA arm, and +1.14 cm (-3.00, 5.09) and +0.13 cm (-3.10, 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.

Conclusion: 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: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV).

Methods: We conducted a qualitative substudy within two parent trials in 24 health facilities in Malawi that enrolled MLHIV ≥15 years not on ART. We conducted in-depth interviews with a stratified random sample of participants who had taken oral ART and self-reported mobility (travel) during the 6-month study (≥1 trip of ≥3 nights). Interviews described cabotegravir/rilpivirine and asked about clients' stated preferences for LAI vs. oral ART and their reasoning. Interviews were translated, transcribed, coded in Atlas.ti, and analyzed using framework analysis.

Results: We interviewed 29 mobile MLHIV from July 1, 2022, to August 30, 2022, median age 36 years (interquartile range: 31-41), mean 28 nights away in the past 6 months (SD: 40). Nearly all participants (26/29) expressed a preference for LAI over daily oral ART because LAI would reduce the risks of forgetting to take pills and unwanted disclosure. Three men preferred oral ART primarily because of fear of side effects from a new medication. A few men reported they would change their preference if injection site reactions prevented them from working.

Conclusions: Mobile MLHIV in Malawi with previous ART adherence challenges expressed strong stated preferences for LAI over daily oral ART. Further research is needed to understand implementation challenges and potential effectiveness of LAI among harder-to-reach populations.

Background: HIV type 1 ((human immunodeficiency virus) HIV-1) elite controllers (ECs) are a rare subset of people living with HIV-1 (PLWH) who control viral replication in the absence of antiretroviral treatment (ART) and may provide a model for a functional cure. We investigated the role of natural killer (NK) cells in HIV-1 ECs from South Africa.

Methods: Phenotypic (CD69, CD38, CD57, PD-1), functional (CD107a, IFN-γ (inferferon gamma)), and nutrient transporter profiles (glucose transporter 1, CD98) of NK cells from ECs (n = 20), viremic progressors (VPs; n = 19), PLWH on ART (n = 20), and people without HIV-1 (PWOH; n = 21) were analyzed using flow cytometry. The Kruskal-Wallis test and followed by the Mann-Whitney U test were used to determine differences among the study groups. The Spearman rank correlation coefficient was used to determine significant associations.

Results: Compared with the other study groups, the percentage of CD69-expressing NK cells was higher in ECs, whereas the percentage of CD38-expressing NK cells was higher in VPs. Percentages of CD69 + CD38 - NK cells were elevated in ECs compared with VPs ( P = 0.003), but were not different to PLWH on ART and PWOH. Differentiation, exhaustion, and metabolic profiles were not different in ECs compared with PLWH on ART and PWOH; however, NK cell function was lower than in PWOH.

Conclusions: These findings demonstrate that NK cells from ECs have an activated, mature profile with low levels of immune exhaustion and a reduced metabolic phenotype suggesting functional competence. This insight could inform the development of novel immunotherapeutic strategies for treating HIV-1.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Nonrepresentative program data may lead to inaccurate estimates of HIV prevalence and treatment coverage for pregnant women.

Setting: One hundred fifty-four countries and subnational locations across 126 countries.

Methods: Using 2023 UNAIDS HIV estimates, we calculated 3 ratios: (1) HIV prevalence among pregnant women to all women 15-49 yrs (prevalence), (2) ART coverage before pregnancy to women 15-49 yrs ART coverage (ART prepregnancy), and (3) ART coverage at delivery to women 15-49 yrs ART coverage (PMTCT coverage). We developed an algorithm to identify and adjust inconsistent results within regional ranges in Spectrum-AIM, illustrated using Burkina Faso estimates.

Results: In 2022, the mean regional ratio of prevalence among pregnant women to all women ranged from 0.68 to 0.95. ART coverage prepregnancy ranged by region from 0.40 to 1.22 times ART coverage among all women. Mean regional PMTCT coverage ratios ranged from 0.85 to 1.51. The prevalence ratio in Burkina Faso was 1.59, above the typical range 0.62-1.04 in western and central Africa. Antenatal clinics reported more PMTCT recipients than estimated HIV-positive pregnant women from 2015 to 2019. We adjusted inputted PMTCT program data to enable consistency of HIV prevalence among pregnant women from programmatic routine HIV testing at antenatal clinics with values typical for western and central Africa.

Conclusions: These ratios offer Spectrum-AIM users a tool to gauge the consistency of their HIV prevalence and treatment coverage estimates among pregnant women with other countries in the region.

Background: Failures in prior rollout of HIV prevention efforts have widened disparities in HIV incidence by race/ethnicity among young sexual minoritized men (YSMM). We hypothesized greater perceptions of medical mistrust would be associated with lower willingness to get an HIV vaccine, mediating the relationship between race/ethnicity and willingness to accept a future HIV vaccine.

Methods: HIV-negative and unknown-status YSMM 17-24 years old (n = 229) recruited through social media and men-for-men networking apps completed online surveys from September 2021 to March 2022. Participants were asked about demographics, medical mistrust (health care-related sexual orientation stigma, health care-related race stigma, global medical mistrust, and trust in health care providers), and willingness to accept a future HIV vaccine.

Results: Vaccine willingness was highest among White YSMM (96.0%) and lower among Black (71.0%), Latino (83.6%), and multiracial or another race/ethnicity YSMM (80.0%). Even after accounting for medical mistrust constructs as mediators, compared with White participants, Black participants had lower odds of being willing to accept a future HIV vaccine. Participants with greater trust in health care providers had higher odds of willingness to accept a future HIV vaccine.

Discussion: Gaps in willingness to get an HIV vaccine are evident among YSMM by race/ethnicity, indicating potential further widening of disparities in HIV incidence when a vaccine becomes available without intervention.

Background: Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TREAT Asia HIV Observational Database) and Australia (Australian HIV Observational Database).

Methods: People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analyzed using repeated measures linear regression. Survival after 10 years was analyzed using competing risk regression.

Results: There were 7139 people included: 4867 (68%) from the TREAT Asia HIV Observational Database and 2272 (32%) from the Australian HIV Observational Database. Higher CD4 levels after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101-200: difference = 35, 95% CI: 18 to 51; >200: difference = 125, 95% CI: 107 to 142) compared with ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL, which subsequently decreased to <500 (difference = 225, 95% confidence interval [CI]: 213 to 236), or in those who achieved and maintained CD4 ≥500 cells/µL (difference = 402, 95% CI: 384 to 420), compared with always <500 in the previous decade. Previous protease inhibitor (PI)-based regimen (difference=-17, 95% CI -33 to -1) compared with no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = -38, 95% CI -62 to -15 and difference=-44, 95% CI -61 to -27, respectively) compared with no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (subhazard ratio = 1.34, 95% CI: 1.04 to 1.71).

Conclusions: Sustaining high CD4 levels and minimizing TI has far-reaching benefits well beyond the first decade of ART.

Background: Patients with lymphoma may require intensive care (ICU) because of disease- or treatment-related complications. The lymphoma-HIV interaction complicates management, but whether outcomes are worse in these patients, when critically ill, is unclear. A retrospective observational cohort study reviewed outcomes of patients admitted to ICU, subsequent 5-year survival, and prognostic factors.

Setting: Academic ICU at the UK National Centre for HIV Malignancy.

Methods: Records between 2007 and 2020 identified the following cohorts: HIV lymphoma, lymphoma alone, HIV alone, and patients without HIV/lymphoma. Patient demographics, lymphoma characteristics, ICU admission data, and survival outcomes were collected. Five-year survival outcomes were analyzed for the lymphoma cohorts. ICU outcomes were analyzed for all cohorts. Descriptive statistics summarized baseline characteristics and outcomes. Multivariate regression identified factors associated with ICU mortality.

Results: Of 5929 patients admitted to the ICU, 63 had HIV lymphoma and 43 had lymphoma alone. Survival to ICU discharge was 71% and 72%, respectively. Adjusted log-odds ratio for ICU survival was significantly better in the comparator cohort. ICU survival between the HIV lymphoma and lymphoma-alone cohorts was not significantly different. Adjusted 5-year survival was not significantly different between lymphoma cohorts. Factors independently associated with a worse ICU survival prognosis were emergency admissions, Acute Physiology and Chronic Health Evaluation II score, initial lactate, and day requiring level 3 support. Mechanical ventilation and higher Acute Physiology and Chronic Health Evaluation II scores were independent risk factors for worse 5-year survival in the lymphoma cohorts.

Conclusions: ICU outcomes and 5-year survival rates of patients with lymphoma were unaffected by HIV status, revealing favorable outcomes in patients with HIV-related lymphoma admitted to the ICU.

Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP.

Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP. The vaginal microbiome, CVF tenofovir concentrations, and CVF inflammatory markers were determined and compared.

Results: The proportion of CVF Lactobacillus was significantly higher in CGW than in TGM (78% vs 24%, P < 0.001). Among TGM, the proportion of CVF Lactobacillus was lower, though not statistically significant, in those taking testosterone than in those not taking testosterone (14% vs 35%, P-value = 0.3). Interestingly, mean CVF tenofovir concentrations were the lowest in TGM on testosterone at 884 ng/mL compared with 3150 ng/mL in TGM not on testosterone and 1932 ng/mL in CGW; however, this difference was not statistically significant. There was no statistically significant difference in any of the genital inflammatory markers between groups and no correlation between inflammation and tenofovir levels.

Conclusions: Our findings suggest a potential correlation between testosterone use, Lactobacillus dominance, and lower TFV concentrations in CVF, which may have implications on HIV acquisition from vaginal sex in TGMT. Future studies with larger sample sizes are needed to further investigate these relationships.

Background: We assessed access to pre-exposure prophylaxis (PrEP) and interest in integration of PrEP with gender-affirmative care in a global sample of transmasculine persons.

Methods: Transmasculine persons (N = 590) aged 18 years and above from 57 countries completed a brief online survey from April to July 2022 about sexual behavior, knowledge, and interest in PrEP, current access to PrEP and gender-affirmative care, and preferred context for accessing PrEP. Descriptive analyses were stratified by country income group.

Results: Most participants (54.4%) lived near a health center offering care to trans people. Overall, 1.9% of respondents reported ever receiving a positive HIV test result. Among those who had not (n = 579), more than a third reported engaging in receptive sex in the past year (35.2%) or anticipated doing so in the next year (41.5%), 86.9% had never received information about HIV prevention specific to transmasculine people, and 76.3% had heard of PrEP. Among those who had heard of PrEP (n = 440), only 18.9% had discussed or been offered it by a provider, and only 3.6% were currently taking it-yet 67.9% who had heard of it but were not using it would "definitely" (28.5%) or "maybe" (39.4%) be interested in taking it were it available for free. Out of these participants, the majority (60.5%) preferred the idea of accessing PrEP from the same clinic where they received gender-affirming care.

Conclusions: Interventions are needed to improve PrEP access for transmasculine people globally. Clinics already providing gender-affirming care to trans people are acceptable clinical contexts to integrate such interventions.