Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome.
OBJECTIVE
To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age.


METHODS
A multicentre, phase I/II, non-randomized, open-label study (PENTA 7).


METHODS
Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated.


RESULTS
Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations.


CONCLUSIONS
Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.
Aboulker
J-P
JP
Babiker
A
A
Chaix
M L
ML
Compagnucci
A
A
Darbyshire
J
J
Debré
M
M
Faye
A
A
Giaquinto
C
C
Gibb
D M
DM
Harper
L
L
Saïdi
Y
Y
Walker
A S
AS
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
D012367:RNA, Viral; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine