Effect of antiretroviral triple combinations including the protease inhibitor nelfinavir in heavily pretreated children with HIV-1 infection.
BACKGROUND
In this retrospective study the effect of antiretroviral triple therapy including the protease-inhibitor nelfinavir (NFV) on CD4-cells and viral load (VL) in heavily pretreated HIV-infected children was evaluated.


METHODS
20 children (<18 years) were included. Median duration of antiretroviral pretreatment was 27 months (range, 7 65), median initial VL was 4.7 log subset 10 (3.2 6.1) and median relative CD4-cells was 17.5% (3 33). Patients were put on combinations with NFV because of treatment failure (increasing VL), intolerance to prior therapy with PIs or adherence problems with prior indinavir. Viral load (RT-PCR, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks.


RESULTS
Median viral load decreased 1.2 log(10) (-1.3 2.5), 0.9 log(10) (-0.8 - 2.5) and 0.4 log(10) (-0.5 - 3.0) after 12, 24 and 36 weeks. The VL of 2 patients was below the detection limit (50 copies/ml) after 24 weeks. The relative CD4-cell count increased from a median of 17.5% to 22%, 23% and 25% after 12, 24 and 36 weeks, respectively. Side effects of NFV were usually mild. WHO grade 1 or 2 diarrhea occurred in 70% and moderate elevations of triglycerides in 40% of the patients. At 48 weeks 18/20 patients had to be switched to other combinations due to virological failure.


CONCLUSIONS
In children with intensive prior antiretroviral therapy combination therapy including NFV lead to a modest short-term reduction of the VL and increase in CD4-cells. However, the long-term antiretroviral effect was poor.
Hoffmann
F
F
Children's Hospital of the Ludwig Maximilians-University, Munich, Germany.
Funk
M
M
Linde
R
R
Notheis
G
G
Petropoulou
T
T
Eberle
J
J
Gürtler
L
L
Belohradsky
B H
BH
Wintergerst
U
U
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D013997:Time Factors; D016312:Treatment Refusal; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019888:Nelfinavir