Risk of extended viral resistance in human immunodeficiency virus-1-infected Mozambican children after first-line treatment failure.
BACKGROUND
Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale.


OBJECTIVE
Assessment of the frequency and profile of resistant virus in HIV-1-infected children, treated for at least 6 months with stavudine/zidovudine + lamivudine + nevirapine and presenting virological failure in a large access program in Maputo, Mozambique.


RESULTS
Cross-sectional evaluation of plasma HIV-1 viral load (VL) in 495 evaluable children among 512 treated for at least 6 months showed that 360 (72.7%) had a VL of <50 copies/mL of HIV-1 RNA. Genotypic resistance tests were performed in the 84 available samples from the 135 treated children with VL > or = 50 copies/mL: 92% of the viruses were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harbored virus with a extended spectrum of cross-resistance defined as resistance to the 3 drugs of the combination received by the child and/or at least 1 resistance to a drug to which the child had never been exposed (abacavir: 5%, tenofovir: 6%, didanosine: 3.5% and the new generation non nucleoside inhibitor, etravirine: 6%). The only factor identified by multivariate analysis as being associated with this extended resistance profile was the duration of treatment (aOR: 6.67 [95% CI: 1.24-35.93], P = 0.015 for treatment >24 months) with a per month increase of 1.09 (1.02-1.16) P = 0.007.


CONCLUSIONS
Residual viral replication in children receiving stavudine/zidovudine + lamivudine + nevirapine treatment is associated with a time-dependent risk of acquiring cross-resistance, including resistance to drugs currently used for second-line treatment and also to the new generation of non nucleoside reverse transcriptase inhibitors.
Vaz
Paula
P
Pediatric Day Hospital at Maputo Central Hospital, Maputo, Mozambique.
Chaix
Marie-Laure
ML
Jani
Ilesh
I
Macassa
Eugenia
E
Bila
Dulce
D
Vubil
Adolfo
A
Anderson
Soren
S
Rouzioux
Christine
C
Briand
Nelly
N
Blanche
Stephane
S
D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D010802:Phylogeny; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018570:Risk Assessment; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase