The Incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies.
BACKGROUND
Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined.


METHODS
Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death.


RESULTS
Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 personyears) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores.


CONCLUSIONS
For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.
Yale University School of Medicine and VA CT Healthcare System, New Haven, Connecticut 06510, USA. Michael.Kozal@yale.edu
Michael J
MJ
Kozal
Katherine Huppler
KH
Hullsiek
Rodger D
RD
Macarthur
Mary van den
Mv
Berg-Wolf
Grace
G
Peng
Ying
Y
Xiang
John D
JD
Baxter
Jonathan
J
Uy
Edward E
EE
Telzak
Richard M
RM
Novak
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000235:genetics*; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D006801:Humans; D015994:Incidence; D010349:Patient Compliance; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents