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Background Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose. Methods We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls. Results Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post–third-dose humoral responses substantially exceeded post–second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post–third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post–third-dose responses. Conclusion PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

To characterize survival and to compare rates of disease progression to death of human immunodeficiency virus (HIV)-infected patients, between those initiating multiple-drug rescue therapy (MDRT) and those antiretroviral-inexperienced initiating triple-drug antiretroviral therapy (ART), we conducted a population-based analysis of HIV-infected men and women aged > or =18 years in British Columbia, Canada. Cumulative mortality rates were estimated by use of Kaplan-Meier methods, and Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival. Cumulative mortality at 36 months was 14.2%+/-2.0% and 10.9%+/-1.0% for the MDRT and triple-drug ART groups, respectively (P=.105, log-rank test). After adjustment for other baseline prognostic variables, MDRT was found not to be a predictor of increased all-cause mortality (relative risk, 1.17; 95% confidence interval, 0.82-1.66) in multivariate analysis. Over the short-term, patients receiving MDRT had relatively low mortality. After adjustment for baseline prognostic factors, rates of survival were comparable with those in patients initiating triple-drug ART.

The steady-state pharmacokinetics of efavirenz and nevirapine, when used in combination to treat human immunodeficiency virus type 1 (HIV-1)-infected subjects, were investigated. HIV-1-infected persons who had used efavirenz (600 mg once daily) for > or =2 weeks were eligible for study inclusion. The plasma pharmacokinetics of efavirenz were determined over 24 h. Subsequently, nevirapine (400 mg once daily) was added to the regimen. After 4 weeks, the pharmacokinetics of efavirenz and nevirapine were assessed over 24 h. The differences between the pharmacokinetic parameters of efavirenz with and without nevirapine were analyzed, and the pharmacokinetics of nevirapine were compared with those in historical control patients. The exposure to efavirenz when combined with nevirapine was significantly decreased by 22% (area under the plasma concentration vs. time curve), 36% (minimum plasma concentration), and 17% (maximum plasma concentration). Nevirapine pharmacokinetics appear to be unaffected by coadministration of efavirenz, compared with data from historical control patients.

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

The goal of the present study was to characterize outcome and predictors of outcome of treatment interruption (TI) in highly active antiretroviral therapy (HAART)-treated patients.A systematic chart/database review was conducted to identify patients with nadir CD4 cell counts200 cells/mm(3) and without acquired immunodeficiency syndrome-defining illnesses who underwent a TI. Collected data included duration and reason for TI, demographic characteristics, CD4 cell count, and plasma viral load. Human immunodeficiency virus (HIV) envelope (V3) loop genotyping was performed on plasma HIV RNA. The presence of basic residues at aa 11 and/or 25 (the "11/25" genotype) was a further possible prognostic variable of interest. Cox proportional hazards models were used to assess characteristics associated with time to HAART reinitiation after TI.A total of 208 of 4461 (4.7%) patients underwent TI. The study group consisted of 197 (94.7%) of 208 participants for whom V3 genotyping was successful. The median CD4 cell count at time of the initiation of TI was 620 cells/mm(3). A total of 59 (29.9%) patients reinitiated HAART after a median of 15 months. At the time of the reinitiation of HAART, the median plasma viral load was100,000 copies/mL, and the median CD4 cell count was 260 cells/mm(3). Among the 197 study patients, there were 6 deaths, none of which was attributable to the TI. A total of 81% had plasma viral loads50 copies/mL by 15 months of follow-up after reinitiation of HAART. In multivariate analysis, a nadir CD4 cell countor =250 cells/mm(3) (risk ratio [RR], 2.79 [95% confidence interval [CI], 1.60-4.86]; P.001) and the presence of the 11/25 genotype (RR, 2.07 [95% CI, 1.07-4.02]; P = .031) were positively and independently associated with faster time to HAART reinitiation, after adjusting for age and plasma virus load at the start of TI.Our study suggests that TI is a viable option for HIV-positive adults with nadir CD4 cell counts250 cells/mm(3). A nadir CD4 cell count of 200-250 cells/mm(3) and the 11/25 viral genotype were found to be associated with a faster HAART reinitiation.