Protease inhibitor resistance in South African children with virologic failure.
BACKGROUND
In South Africa, first-line antiretroviral therapy for children younger than 3 years of age combines a protease inhibitor (PI) with 2 nucleoside reverse transcription inhibitors. In our study, some pediatric patients received ritonavir (RTV) as single PI (RTV-sPI) and others ritonavir-boosted lopinavir (LPV/r), which has a higher resistance barrier. We explored antiretroviral resistance mutations in pediatric patients failing PI-based antiretroviral therapy and the predictors of major PI resistance mutations (MPIRM) in these patients.


METHODS
We studied pediatric HIV patients at Tygerberg Academic Hospital experiencing virologic failure on a PI regimen. Mixed-effects linear- and mixed-effect logistic regression modeling, were used to explore predictors of MPIRM.


RESULTS
MPIRM were found in 12 of 17 patients exposed to RTV-sPI compared with 1 of 13 patients treated with LPV/r. Exposure to RTV-sPI was significantly associated with MPIRM, with both exposure time and estimated failing time on RTV-sPI being significant positive predictors of MPIRM. Neither CD4 count, viral load, age at first visit nor receiving rifampin predicted MPIRM.


CONCLUSIONS
RTV-sPI in infants and children poses a significant risk of MPIRM which is dependent on the exposure time and time failing while receiving the regimen.
van Zyl
Gert U
GU
Centre for Infectious Diseases, Division of Medical Virology, Tygerberg and Stellenbosch University, Cape Town, South Africa. guvz@sun.ac.za
van der Merwe
Lize
L
Claassen
Mathilda
M
Cotton
Mark F
MF
Rabie
Helena
H
Prozesky
Hans W
HW
Preiser
Wolfgang
W
D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012044:Regression Analysis; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
D044966:Anti-Retroviral Agents; D011480:Protease Inhibitors; D019438:Ritonavir