Viral rebound and emergence of drug resistance in the absence of viral load testing: a randomized comparison between zidovudine-lamivudine plus Nevirapine and zidovudine-lamivudine plus Abacavir.
BACKGROUND
We investigated virological response and the emergence of resistance in the Nevirapine or Abacavir (NORA) substudy of the Development of Antiretroviral Treatment in Africa (DART) trial.


METHODS
Six hundred symptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected adults (CD4 cell count, <200 cells/mm(3)) from 2 Ugandan centers were randomized to receive zidovudine-lamivudine plus abacavir or nevirapine. Virology was performed retrospectively on stored plasma samples at selected time points. In patients with HIV RNA levels >1000 copies/mL, the residual activity of therapy was calculated as the reduction in HIV RNA level, compared with baseline.


RESULTS
Overall, HIV RNA levels were lower in the nevirapine group than in the abacavir group at 24 and 48 weeks (P < .001), although no differences were observed at weeks 4 and 12. Virological responses were similar in the 2 treatment groups for baseline HIV RNA level <100,000 copies/mL. The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations (TAMs) and M184V (1.47 log(10) copies/mL) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations, whether accompanied by TAMs (0.96 log(10) copies/mL) or not (1.18 log(10) copies/mL).


CONCLUSIONS
There was more extensive genotypic resistance in both treatment groups than is generally seen in resource-rich settings. However, significant residual activity was observed among patients with virological failure, particularly those receiving zidovudine-lamivudine plus abacavir.
Ndembi
Nicaise
N
Uganda Research Unit on AIDS, Medical Research Council (MRC)-Uganda Virus Research Institute, Entebbe, Kampala, Uganda.
Ndembi
Nicasie
N
Goodall
Ruth L
RL
Dunn
David T
DT
McCormick
Adele
A
Burke
Andy
A
Lyagoba
Fred
F
Munderi
Paula
P
Katundu
Pauline
P
Kityo
Cissy
C
Robertson
Val
V
Yirrell
David L
DL
Walker
A Sarah
AS
Gibb
Diane M
DM
Gilks
Charles F
CF
Kaleebu
Pontiano
P
Pillay
Deenan
D
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D012367:RNA, Viral; D014454:Uganda; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D044966:Anti-Retroviral Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D019829:Nevirapine; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir