Incident AIDS or Death After Initiation of Human Immunodeficiency Virus Treatment Regimens Including Raltegravir or Efavirenz Among Adults in the United States

Abstract

Background.: The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown.

Methods.: We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates.

Results.: At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]).

Conclusions.: Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

Keywords: HIV; cohort study; comparative effectiveness; mortality.; raltegravir.

Figure 1.

Risk of incident AIDS or death from any cause over 4 years from treatment initiation among 3061 human immunodeficiency virus–infected adults in care between 12 October 2007 and 1 October 2015. Solid line represents the efavirenz regimen, and dashed line represents the raltegravir regimen. Upper panels represent intent-to-treat analyses with the left panel depicting the crude results, and right panel the inverse probability (IP)–weighted results (accounting for nonrandom sampling, treatment allocation, and dropout). Lower panels represent per-protocol analyses with the left panel again representing crude results, and the right panel the IP-weighted results (accounting for nonrandom sampling, treatment allocation, dropout, and treatment changes).