BACKGROUND: Cardiometabolic diseases are risk factors for COVID-19 severity. The extent that cardiometabolic health represents a modifiable factor to mitigate the short- and long-term consequences from SARS-CoV-2 remains unclear. Our objective was to evaluate the associations between intraindividual variability of cardiometabolic health indicators and COVID-19 related hospitalizations and post-COVID conditions (PCC) among a relatively healthy population. METHODS: This retrospective, multi-site cohort study was a post-hoc analysis among individuals with cardiometabolic health data collected during routine blood donation visits in 24 US states (2009-2018) and who responded to COVID-19 questionnaires (2021-2023). Intraindividual variability of blood pressure (systolic, diastolic), total circulating cholesterol, and body mass index (BMI) were defined as the coefficient of variation (CV) across all available donation timepoints (ranging from 3 to 74); participants were categorized into CV quartiles. Associations were evaluated by multivariable binomial regressions. RESULTS: Overall, 3344 participants provided 42,090 donations (median 9 [IQR 5, 17]). The median age was 48 years (38, 56) at the first study donation. 1.2% (N = 40) were hospitalized due to COVID-19 and 15.5% (N = 519) had PCC. Higher BMI variability was associated with greater risk of COVID-19 hospitalization (4th quartile aRR 4.15 [95% CI 1.31, 13.11], p = 0.02; 3rd quartile aRR 3.41 [95% CI 1.09, 10.69], p = 0.04). Participants with higher variability of BMI had greater risk of PCC (4th quartile aRR 1.29 [95% CI 1.02, 1.64]; p = 0.04). Intraindividual variability of blood pressure (systolic, diastolic) and total circulating cholesterol were not associated with COVID-19 hospitalization or PCC risk (all p > 0.05). From causal mediation analysis, the association between the highest quartiles of BMI variability and PCC was not mediated by hospitalization (p > 0.05). CONCLUSIONS: Higher intraindividual variability of BMI was associated with COVID-19 hospitalization and PCC risk. Our findings underscore the need for further elucidating mechanisms that explain these associations and importance for consistent maintenance of body weight.

We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35-1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24-5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09-4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09-1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services.

We assessed the role of depressive symptoms on adherence to daily oral FTC/TDF for HIV PrEP in cisgender men who have sex with men (MSM) and transgender women who have sex with men (TGW) using data from the iPrEx OLE study. A marginal structural logistic regression model was used to estimate the effect of time-varying CES-D scores on having protective levels of drug concentration, adjusting for confounding by sexual practices over time, prior adherence, and baseline demographic characteristics. We found a non-monotonic relationship between CES-D score and odds of protective FTC/TDF levels in MSM. We found evidence that the effect of depression on adherence varied between MSM and TGW, and that depressive symptoms did not contribute greatly to decreased adherence on a population scale. We recommend that depressive symptoms not preclude the prescription of PrEP, and that MSM and TGW be studied separately.

Background

HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.

Methods

We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.

Results

12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.

Conclusions

HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

BACKGROUND: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening. METHODS: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP). RESULTS: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was <100% at all timepoints, and lower among those initiating ART earlier. Seroreversions occurred for 29% (16/55), and blood donation screening with NAT and Ag/Ab assays could have missed up to 36% (20/55) of RV254 participants. For SIPP participants, who started ART at later timepoints, Ag/Ab assays identified infections with no evidence of reactivity waning. CONCLUSION: PrEP and early ART initiation can delay or reduce HIV detectability. Considerations for the implementation of NAT and Ag/Ab tests in PrEP/PEP programs relying on Ab-only RDTs should be balanced according to feasibility and public health impact. While blood transfusion services using Ab-only RDTs for HIV screening should adopt higher sensitivity tests, surveillance and further research are needed to determine the need for novel HIV testing algorithms for those already using NAT and Ag/Ab screening assays.