JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Re-engaging people with HIV who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals.

Methods: A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard of care where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N = 333) or standard of care (N = 322). HIV care continuum outcomes included re-engagement at 90 days, retention in care, and viral suppression by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes.

Results: Participants randomized to DIS were more likely to be re-engaged at 90 days (adjusted odds ratios [aOR] = 1.42, P = 0.045). Independent predictors of re-engagement at 90 days were age older than 40 years (aOR = 1.84, P = 0.012) and perinatal HIV risk category (aOR = 3.19, P = 0.030). Predictors of retention at 12 months included re-engagement at 90 days (aOR = 10.31, P < 0.001), drug injection HIV risk category (aOR = 1.83, P = 0.032), detectable HIV-1 RNA before randomization (aOR = 0.40, P = 0.003), and county (Hartford aOR = 1.74, P = 0.049; New Haven aOR = 1.80, P = 0.030). Predictors of viral suppression included re-engagement at 90 days (aOR = 2.85, P < 0.001), retention in HIV care (aOR = 7.07, P < 0.001), and detectable HIV-1 RNA prerandomization (aOR = 0.23, P < 0.001).

Conclusions: A D2C strategy significantly improved re-engagement at 90 days. Early re-engagement improved downstream benefits along the HIV care continuum like retention in care and viral suppression at 12 months. Moreover, other factors predictive of care continuum outcomes can be used to improve D2C strategies.

Background: Late diagnosis of HIV infection is a major global problem. In Turkiye, only 41%-50% of people living with HIV are diagnosed, suggesting that many opportunities for HIV testing might be missed.

Setting: The aim of this study was to determine the missed testing opportunities for HIV in healthcare settings in Turkiye and the predictors for missed opportunities (MOs).

Methods: The study included patients with a new HIV diagnosis, presenting to care between January 2018 and December 2020. They were given a verbal questionnaire face to face, by a telephone call or an online meeting for visits to a health care setting within the year before their diagnosis. Electronic medical records were also examined.

Results: The sample included 198 patients with at least 1 visit to any health care setting, with a total of 1677 visits. Patients had an indication for HIV testing in 51.3% (861/1677) of the visits; an HIV test was not offered in 77.9% (671/861) and was considered a MO. The highest number of MOs was in emergency departments (59.8%) (180/301). The most common reason for visiting was constitutional symptoms and indicator conditions (55.4%) (929/1677). University graduates and those with a CD4+ T-cell count <200/mm 3 were more likely to have a MO.

Conclusions: Many opportunities to diagnose HIV at an early stage are missed in health care settings in Turkiye. Considering the rapidly increasing number of new diagnoses in the last decade, urgent action needs to be taken.

Background: The Integration of cardiovascular disease SCreening and prevention in the HIV MAnagement plan for women of reproductive age study set out to determine the effectiveness of screening and lifestyle modification in modifying cardiovascular disease (CVD) risk factors in women living with HIV (WLHIV).

Methods: In this prospective, quasiexperimental, intervention study, WLHIV aged 18-<50 years were enrolled from 2 clinics (intervention [I-arm]) and (control arms [C-arm]) in Umlazi, South Africa, between November 2018 and May 2019. Women in the I-arm received lifestyle modification advice on diet, physical activity, alcohol use, and smoking cessation and underwent annual screening for CVD risk. The CVD risk factors were assessed through standardized questionnaires and clinical and laboratory procedures at baseline and at end of 3 years of follow-up. Prevalence of metabolic syndrome and other CVD indices were compared between arms at end-of-study (EOS).

Results: Total of 269 WLHIV (149 I-arm and 120 C-arm) with a mean ± SD age of 36 ± 1 years were included in the EOS analyses after 32 ± 2 months of follow-up. The metabolic syndrome prevalence at EOS was 16.8% (25/149) in the I-arm and 24% (24/120) in the C-arm (risk ratio 0.9; 95% CI: 0.5 to 1.1; P 0.86). Proportion of women with fasting blood glucose >5.6 mmol/L in the I-arm and C-arm were 2.7% (4/149) and 13.3% (16/120) respectively (risk ratio 0.2; 95% CI: 0.069 to 0.646; P < 0.01). High-density lipoprotein improved with the intervention arm from baseline to EOS (95% CI: -0.157 to -0.034; P < 0.05).

Conclusions: Although there was no significant difference in the prevalence of metabolic syndrome between study arms, we observed decreased blood glucose levels in the I-arm compared with the C-arm and improved high-density lipoprotein within the I-arm, following lifestyle modification and regular screening for CVD risk factors in WLHIV.

Abstract: There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex- and race-matched cohort of people with HIV (PWH, n = 20) and people without HIV (PWOH, n = 41). We performed flow cytometric analyses on peripheral blood mononuclear cells from PWH and PWOH experiencing acute COVID-19 (≤21-day postsymptom onset). PWH were younger (median 52 vs 65 years) and had milder COVID-19 (40% vs 88% hospitalized) compared with PWOH. Flow cytometry panels included surface markers for immune cell populations, activation and exhaustion surface markers (with and without SARS-CoV-2-specific antigen stimulation), and intracellular cytokine staining. We observed that PWH had increased expression of activation (eg, CD137 and OX40) and exhaustion (eg, PD1 and TIGIT) markers as compared to PWOH during acute COVID-19. When analyzing the impact of COVID-19 severity, we found that hospitalized PWH had lower nonclassical (CD16 + ) monocyte frequencies, decreased expression of TIM3 on CD4 + T cells, and increased expression of PDL1 and CD69 on CD8 + T cells. Our findings demonstrate that PWH have increased immune activation and exhaustion as compared to a cohort of predominately older, hospitalized PWOH and raises questions on how chronic immune activation affects acute disease and the development of postacute sequelae.

Objective: We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia.

Methods: Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed.

Results: Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits.

Conclusion: We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.

Background: Long-acting (LA) antiretrovirals may provide meaningful benefit to people who use drugs and people experiencing homelessness (PEH) who face disproportionate structural and psychosocial barriers in adhering to daily oral HIV antiretroviral therapy or pre-exposure prophylaxis (PrEP), but their use in these populations has not been studied.

Setting: The Maria X. Martinez Health Resource Center is a low-barrier (eg, no appointment) community-based clinic serving San Francisco PEH.

Methods: A multidisciplinary care model with robust monitoring and outreach support was developed to provide LA antiretroviral therapy (ART) and LA-PrEP to eligible patients experiencing difficulties adhering to oral antiretrovirals. Feasibility was assessed by evaluating the rates of HIV viremia and on-time injections among patients receiving LA antiretrovirals over the first 24 months of program implementation.

Results: Between November 2021 and November 2023, 33 patients initiated LA-ART or LA-PrEP (median age, 37 years; 27% transgender/nonbinary; 73% non-White; 27% street homeless; 52% sheltered homeless; 30% with opioid use disorder; 82% with methamphetamine use disorder). Among 18 patients with HIV, 14 initiated LA-ART injections with detectable viremia (median CD4 count, 340 cells/mm 3 ; mean log 10 viral load, 3.53; SD, 1.62), 8 had never previously been virally suppressed, and all but 1 achieved or maintained virologic suppression (mean, 9.67 months; SD, 8.30). Among 15 LA-PrEP patients, all remained HIV negative (mean, 4.73 months; SD, 2.89). Of 224 total injections administered, 8% were delayed >7 days.

Discussion: The implementation of LA antiretrovirals is feasible in low-barrier, highly supportive clinical settings serving vulnerable PEH. Expansion of such programs will be critical in ending the HIV epidemic.

Background: With few psychometrically evaluated HIV-related stigma measures for adolescents and young adults living with HIV, we examined the developmental applicability (ie, validity) of 2 subscales of the commonly used stigma measure, the Social Impact Scale, among a cohort of adolescents and young adults with perinatally acquired HIV.

Setting: Data were obtained from a New York City longitudinal study (N = 340). This study primarily comprised Black and Latinx adolescents and young adults with either perinatally acquired HIV or those with perinatal exposure but who are uninfected. Data for this analysis were obtained from the population with perinatally acquired HIV and spanned approximately a 15-year survey period (2003-2018).

Methods: A confirmatory factor analysis was used at 7 time points to assess whether the Social Rejection and Internalized Shame subscales were consistent in this cohort over time. Overall and individual Cronbach alphas were reported to show the strength of the internal consistency.

Results: The mean age from baseline to follow-up 6 ranged from 12 to 23 years over the study period. The Social Rejection subscale was acceptably valid across follow-up periods with strong factor loadings and Cronbach alphas higher than 0.70. However, the Internalized Shame subscale was less valid among younger adolescents. Starting at follow-up 2, we observed better validity with the Internalized Shame subscale performance.

Conclusion: Future research must consider mechanisms for developing and adapting measures from a developmental perspective to best measure the experiences of HIV-related stigma among younger populations.

Background: Dolutegravir exposure is reduced after switching from efavirenz, which could select for dolutegravir resistance if switching occurs during virologic failure.

Methods: We measured serial dolutegravir trough concentrations after switching from efavirenz in a clinical trial, which randomized some participants to a supplemental dolutegravir dose or placebo for the first 14 days. Changes in dolutegravir trough concentrations between days 3, 7, 14, and 28 were evaluated. The primary outcome was the geometric mean ratio of dolutegravir trough concentrations on day 7 versus day 28.

Results: Twenty-four participants received double-dose dolutegravir (50 mg twice daily) and 11 standard dose for the first 14 days. Baseline characteristics were 77% female, median age 36 years, CD4 cell count 254 cells/mm3, and HIV-1 RNA 4.0 log10 copies/mL. The geometric mean ratio (90% CI) of dolutegravir trough concentrations on day 7 versus day 28 was 0.637 (0.485 to 0.837) in the standard-dose group and 1.654 (1.404 to 1.948) in the double-dose group. There was a prolonged induction effect at day 28 in participants with efavirenz slow metaboliser genotypes. One participant in the double-dose group had a dolutegravir trough concentration below the protein-binding adjusted concentration needed to inhibit 90% of HIV-1 (PA-IC90) at day 3.

Conclusions: No participants on standard-dose dolutegravir had dolutegravir trough concentrations below the PA-IC90. Slow efavirenz metaboliser genotypes had higher baseline efavirenz concentrations and more pronounced and longer period of induction postswitch. These findings suggest that a 14-day lead-in supplemental dolutegravir dose may not be necessary when switching from a failing efavirenz-based first-line regimen.