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.
Centre for Infectious Diseases, Division of Medical Virology, Tygerberg and Stellenbosch University, Cape Town, South Africa. guvz@sun.ac.za
Gert U
GU
van Zyl
Lize
L
van der Merwe
Mathilda
M
Claassen
Mark F
MF
Cotton
Helena
H
Rabie
Hans W
HW
Prozesky
Wolfgang
W
Preiser
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