Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line treatment in HIV-1-infected children in Mali.
OBJECTIVE
To evaluate the virological response and to describe the resistance profiles in the case of failure after 6 months of first-line highly active antiretroviral therapy (HAART) in HIV-1-infected children living in resource-limited settings.


METHODS
Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. Virological failure (VF) was defined as loss to follow-up, death or HIV-1 RNA viral load (VL) of >400 copies/mL at 6 months. When VL was >50 copies/mL, a genotypic resistance test was performed.


RESULTS
Among the 97 children, median age at antiretroviral initiation was 31 months and the majority were in WHO clinical (77.3%) and immunological (70.1%) stage III or IV. At month 6, 44% of children had VL > 400 copies/mL (61% VF). Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). At failure, 6/8 children with wild-type viruses had a VL of <1000 copies/mL whereas 21/22 with resistant viruses had a VL of >1000 copies/mL.


CONCLUSIONS
Under NNRTI-based regimens, early detection of VF could allow the reinforcement of adherence when VL was <1000 copies/mL, because in most of these cases no resistance mutations were detected, or a change to a protease inhibitor-based regimen if VL was >1000 copies/mL. The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure.
Germanaud
David
D
SOLTHIS, Bamako, Mali.
Derache
Anne
A
Traore
Mamadou
M
Madec
Yoann
Y
Toure
Safiatou
S
Dicko
Fatoumata
F
Coulibaly
Hadizatou
H
Traore
Malick
M
Sylla
Mariam
M
Calvez
Vincent
V
Marcelin
Anne-Genevieve
AG
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008302:Mali; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase