No abstract

The advent of combination antiretroviral therapy has led to significant improvement in the care of HIV-infected patients. Originally designed as a protease inhibitor (PI), ritonavir is currently exclusively used as a pharmacokinetic enhancer of other protease inhibitors, predominantly due to ritonavir's potent inhibition of the cytochrome P450 3A4 isoenzyme. Ritonavir-boosting of PIs decrease pill burden and frequency of dosing. Boosted PIs are recommended for first-line therapy in treatment and play a key role in the management of treatment-experienced patients. Potential problems associated with PIs include metabolic abnormalities (e.g. dyslipidemia), increased cardiovascular risk, and drug interactions.

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm3, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

Background & Aims: Despite the high burden of hepatitis C virus (HCV) infection among people who inject drugs (PWID), uptake of interferon-based therapies has been extremely low. Increasing availability of direct-acting antiviral (DAA)-based therapies offers the possibility of rapid treatment expansion with the goal of controlling the HCV epidemic. We evaluated DAA-based treatment uptake among HCVpositive PWID in Vancouver after introduction of DAAs in the government drug formulary. Methods: Using data from three cohorts of PWID in Vancouver, Canada, we investigated factors associated with DAA-therapies uptake among participants with HCV Results: Of the 915 HCV-positive PWID, 611 (66.8%) were recent PWID and 369 (40.3%) had HIV coinfection. During the study period, 146 (16.0%) initiated DAA-therapies, a rate of 6.0 per 100 person-year, with higher initiation rates among non-recent PWID and an increasing trend over time. In multivariable analysis, HIV coinfection (Adjusted Odds Ratio [AOR] = 2.29, 95% Confidence Interval [CI]: 1.55-3.40), white race (AOR = 1.56, 95% CI: 1.05-2.35), and engagement in HCV care (AOR = 1.94, 95%CI: 1.31-2.90) were positively associated with DAA-therapies uptake, while high-risk drinking (AOR = 0.47, 95% CI: 0.23-0.88) and daily crack use were negatively associated (AOR = 0.41, 95% CI: 0.17-0.85). Among recent PWID, engagement in opioid agonist therapy emerged as an independent correlate of DAA uptake. Conclusions:Despite increases in HCV treatment uptake among PWID after the introduction of DAAs in our setting, disparities in access remain. Social-structural and behavioural barriers to HCV care should be addressed for the success of any HCV elimination strategy.