Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial

Abstract

Background: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.

Methods: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.

Results: A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.

Conclusions: There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.

Clinical trials registration: NCT02344290.

Keywords: CD4 cell count; CD4/CD8 ratio; HIV; REPRIEVE; antiretroviral therapy; cardiovascular disease; pitavastatin calcium; statins.

Figure 1.

Class of entry regimen stratified by Global Burden of Disease region. Only regimens and agents with frequency >5 % of participants are shown. Abbreviations: ABC, abacavir; ATV, atazanavir; BIC, bictegravir; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; ETR, Etravirine; FPV, fos-amprenavir; INSTI, integrase strand transfer inhibitor; LPV, lopinavir; NNRTI, nonnucleoside reverse-transcriptase inhibitor; NRTI, nucleoside/nucleotide reverse-transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; RAL, raltegravir; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; ZDV, zidovudine.

Figure 2.

Changes in entry regimen class by time of enrollment. Top panels show the numbers of participants; lower panels, the percentages participants (calculated within each bar). Within each panel, enrollment quarter with a frequency <3 within a panel not shown. Abbreviations: INSTI, integrase strand transfer inhibitor; NNRTI, nonnucleoside reverse-transcriptase inhibitor; NRTI, nucleoside/nucleotide reverse-transcriptase inhibitor; PI, protease inhibitor; Q2, quarter 2; Q4, quarter 4.

Figure 3.

Adjusted regression analyses on CD4 T-cell count (A), CD8 T-cell count (B), and low (<1) CD4/CD8 ratio (C). Abbreviations: ART, antiretroviral therapy; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CI, confidence interval; Est = Estimate, and Ref = Reference; GBD, Global Burden of Disease; INSTI, integrase strand transfer inhibitor; NRTI, nucleoside/nucleotide reverse-transcriptase inhibitor; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor; Ref, reference.