JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

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.

Background: Non-AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan.

Setting: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021.

Methods: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021.

Results: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals.

Conclusions: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.

Background: Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied.

Methods: We analyzed data from a cohort study of 165 antiretroviral therapy (ART)-naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009 to 2013. Twenty-nine plasma biomarkers were measured pre-ART and 4 weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (body mass index <18.5 kg/m 2 ), and clinical outcomes.

Results: PCA identified 5 principal components with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI: 0.02 to 0.36) and post-ART (0.24, 95% CI: 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, interleukin (IL)-12p40, vascular endothelial growth factor, IL-1α, and IL-8 and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI: 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10 and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI: 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI: 0.6 to 8.9) were associated with death in adjusted models.

Discussion: We identified 2 distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and tuberculosis. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes.

Introduction: Large proportions of people living with HIV (PLHIV) in sub-Saharan Africa are not linked to or retained in HIV care. There is a critical need for cost-effective interventions to improve engagement and retention in care and inform optimal allocation of resources.

Methods: We estimated costs associated with a short message service (SMS) plus peer navigation (SMS+PN) intervention; an SMS-only intervention; and standard of care (SOC), within the I-Care cluster-randomized trial to improve HIV care engagement for recently diagnosed PLHIV. We employed a uniform cost data-collection protocol to quantify resources used and associated costs for each intervention.

Results: Compared with SOC, the SMS+PN intervention cost $1284 ($828-$2859) more per additional patient linked to care within 30 days and $1904 ($1158-$5343) more per additional patient retained in care at 12 months, while improving linkage by 24% (95% CI: 11 to 36) and retention by 16% (95% CI: 6 to 26). By contrast, the SMS-only intervention cost $198 ($93-dominated) more per additional patient linked to care and $697 ($171-dominated) more per additional patient retained in care but was not significantly associated with improvements in linkage (12%; 95% CI: -1 to 25) or retention (3%; 95% CI: -7 to 14) compared with SOC. The efficiency of the SMS+PN intervention could be improved by 46%, to $690 more per additional patient linked and $1023 more per additional patient retained in care, if implemented within the Department of Health using more efficient distribution of staff resources.

Discussion: Findings suggest that scale-up of the SMS+PN intervention could benefit patients, improving care and health outcomes while being cost-effective.

Background: HIV is associated with alterations in androgen hormone levels and sex hormone-binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen hormones, SHBG, and menopausal phase to diabetes is unclear.

Methods: From April 2003 through February 2020, 896 women with HIV (WWH) and 343 women without HIV (WWOH) from the Women's Interagency HIV Study with morning total testosterone, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels were followed to assess for incident diabetes. Parametric regression models were used with age as the time scale and relative times (RT) as the measure of association of hormone level and menopausal phase with incident diabetes. Analyses incorporated time-dependent androgen hormone, SHBG levels, and menopausal phase and were adjusted for race/ethnicity, enrollment year, smoking status, BMI, hepatitis C virus status, and HIV-related factors.

Results: In total, 128 (14%) WWH and 47 (14%) WWOH developed diabetes. In WWH, a doubling of SHBG and DHEAS were associated with a 7% (RT = 1.07 [95% CI: 0.82 to 1.40] and 15% (RT = 1.15 [95% CI: 0.95 to 1.39]) longer time to diabetes, respectively; in WWOH, a doubling of SHBG and DHEAS were associated with 84% (RT = 1.84 [95% CI: 0.89 to 3.82]) and 41% (RT= 1.41 [95% CI: 0.82 to 2.44]) longer times to diabetes. Total testosterone was not associated. In WWH, later menopausal phase was associated with shorter times to diabetes.

Conclusions: Despite alterations in androgen hormone and SHBG levels in HIV, regardless of HIV status, higher SHBG and DHEAS were associated with nonstatistically significant slower progression to diabetes. The menopausal transition may be a better hormonal indicator of diabetes risk in WWH.

Background: Vascular aging, a precursor of arterial stiffness, is associated with neurocognitive impairment (NCI) and cardiovascular disease. Although HIV is associated with rapid vascular aging, it is unknown whether arterial stiffness mediates changes in cognitive function. We explored whether estimated markers of vascular aging were associated with NCI indices in HIV-positive individuals.

Methods: This study was a secondary analysis of an observational study. Neurocognitive functioning was assessed using a battery of 7 domains (verbal fluency, executive functioning, speed of information processing, attention/working memory, memory [learning and delayed recall], and motor skills). Vascular aging was assessed using estimated markers of arterial stiffness (ie, estimated pulse wave velocity, pulse pressure, and vascular overload index). A multivariable regression adjusted for demographics, cardiovascular disease risk factors, and HIV clinical variables was used to examine the association between vascular aging and NCI outcomes.

Results: Among 165 people with HIV, the mean age was 51.5 ± 6.9 years (62% men and 83% African American/Black or Other). In fully adjusted models, an increase in estimated pulse wave velocity and pulse pressure was associated with lower T scores in learning (-2.95 [-5.13, -0.77]) and working memory (-2.37 [-4.36, -0.37]), respectively. An increase in vascular overload index was associated with lower T scores in working memory (-2.33 [-4.37, -0.29]) and learning (-1.85 [-3.49, -0.21]).

Conclusions: Estimated markers of arterial stiffness were weakly associated with neurocognitive functioning, suggesting that vascular aging may have a role in cognitive decline among people with HIV.

Background: Pregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care.

Setting: Rural Kenya and Uganda.

Methods: Women (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation.

Results: Between April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001).

Conclusion: A person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.