Efavirenz versus nevirapine-based initial treatment of HIV infection: clinical and virological outcomes in Southern African adults.
OBJECTIVE
To determine the effectiveness of efavirenz versus nevirapine in initial antiretroviral therapy regimens for adults in sub-Saharan Africa.


METHODS
Observational cohort study.


METHODS
Study participants were 2817 HIV-infected, highly active antiretroviral therapy-naive adults who began nevirapine-based or efavirenz-based highly active antiretroviral therapy between January 1998 and September 2004 via a private-sector HIV/AIDS program in nine countries of southern Africa. The primary outcome was time to virologic failure (two measurements of viral loads >or=400 copies/ml). Secondary outcomes included all-cause mortality, time to viral load less than 400 copies/ml, pharmacy-claim adherence, and discontinuation of nevirapine or efavirenz without virologic failure.


RESULTS
The median follow-up period was 2.0 years (interquartile range 1.2-2.6). Patients started on nevirapine were significantly less likely than those started on efavirenz to achieve high adherence, whether defined as 100% (30.2 versus 38.1%, P < 0.002) or more than 90% (44.8 versus 49.4%, P < 0.02) pharmacy-claim adherence. In a multivariate analysis, patients on nevirapine had greater risk of virologic failure [hazard ratio (HR 1.52; 95% confidence interval (CI) 1.24-1.86)], death (2.17; 1.31-3.60), and regimen discontinuation (1.67; 1.32-2.11). Switching from nevirapine to efavirenz had no significant virologic effect, whereas switching from efavirenz to nevirapine resulted in significantly slower time to suppression (hazard ratio 0.58, 95% confidence interval 0.35-0.93) and faster time to failure (hazard ratio 3.92; 95% confidence interval 1.61-9.55) than remaining on efavirenz.


CONCLUSIONS
In initial highly active antiretroviral therapy regimens, efavirenz was associated with superior virologic and clinical outcomes than nevirapine, suggesting that efavirenz might be the preferred nonnucleoside reverse transcriptase inhibitor in resource-limited settings. However, its higher cost and potential teratogenicity are important barriers to implementation.
Nachega
Jean B
JB
Department of Internal Medicine and Center for Infectious Disease, Stellenbosch University, Cape Town, South Africa. jnachega@sun.ac.za
Hislop
Michael
M
Dowdy
David W
DW
Gallant
Joel E
JE
Chaisson
Richard E
RE
Regensberg
Leon
L
Maartens
Gary
G
D000328:Adult; D000353:Africa, Southern / Q000453:epidemiology; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003521:Cyclopropanes; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use*; D010349:Patient Compliance; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz