Changes in renal and metabolic indices after switching from tenofovir disoproxil fumarate- to tenofovir alafenamide-containing ART among individuals with HIV in Canada: A retrospective study.

We assessed renal and metabolic changes associated with switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens among patients with HIV at the Maple Leaf Medical Clinic, Toronto, Canada. Using an electronic medical records retrospective chart review from July 2005 to December 2019, 651 patients aged ≥16 years taking TDF-containing regimens for ≥6 months who switched to TAF-containing regimens for ≥6 months were included. Change in estimated glomerular filtration rate (eGFR) was examined at 12-month follow-up. Secondary outcomes included change in urine albumin-to-creatinine ratio, serum phosphate, alkaline phosphatase (ALP), cholesterol markers, HbA1C, and weight. After 12 months, eGFR increased in 63% of the baseline eGFR <60 mL/min/1.73 m2 group (mean change [SD] = +5.1 [10.8], p = 0.002), 52% for the baseline eGFR = 60-90 mL/min/1.73 m2 group (+0.5 [10.4], p = 0.490), and 26% for baseline eGFR >90 mL/min/1.73 m2 group (-7.2 [11.2], p <0.001). The multivariable generalized estimating equations model showed a significant reduction in eGFR after 12 months. Advanced age, HCV coinfection, and being switched to or on integrase inhibitors were significantly associated with reduced eGFR. Among secondary outcomes, ALP significantly decreased, while high-density lipoprotein, low-density lipoprotein, and weight significantly increased. Our findings suggest that TDF-to-TAF switching was beneficial for those with preexisting renal impairment (eGFR <60 mL/min/1.73 m2).

Assessment of antiretroviral third agent virologic durability after initiation of first antiretroviral regimen.

Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan-Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30-45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4-5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1-5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217-440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan-Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18-0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47-0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47-0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17-0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58-2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.

Cohort profile: the Ontario HIV Treatment Network Cohort Study (OCS).

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).

Immunologic effectiveness of maraviroc- and raltegravir-containing regimens (R+M+) versus raltegravir-based regimens that do not include maraviroc (R+M-).

OBJECTIVE: To compare the immunologic effectiveness of raltegravir-maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M-) in treatment-experienced patients in clinical practice. METHODS: We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M--based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model. RESULTS: One hundred and fifty-six patients were included in the analysis, of whom 32 were receiving R+M+ and 124 R+M-. Mean baseline CD4 counts in patients on R+M+ and R+M- were 463.8 and 442.3 cells/mm(3), respectively (P = .67). In multivariable mixed models, a baseline viral load ≥50 copies/mL was significantly associated with CD4 change during follow-up (P < .0001). No difference between R+M+ and R+M- was observed during follow-up (P = .81). CONCLUSION: CD4 cell recovery was similar among patients receiving either R+M+- or R+M--based therapy during a 24-month period of follow-up.