JAC Advance Access published online on November 19, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp412
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Original research |
Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line treatment in HIV-1-infected children in Mali
1 SOLTHIS, Bamako, Mali 2 Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC Univ Paris 06, INSERM U943, 83 Boulevard de l'Hôpital, 75013 Paris, France 3 Hôpital Gabriel Touré, Bamako, Mali 4 Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France 5 Institut National de Recherche en Santé Publique, Bamako, Mali
Received 1 September 2009; returned 11 October 2009; revised 15 October 2009; accepted 18 October 2009
* Corresponding author. Tel: +33-1-42-17-74-01; Fax: +33-1-42-17-74-11; E-mail: anne-genevieve.marcelin{at}psl.aphp.fr
Objectives: To evaluate the virological response and to describe the resistance profiles in the case of failure after 6 months of first-line highly active antiretroviral therapy (HAART) in HIV-1-infected children living in resource-limited settings.
Patients and methods: Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. Virological failure (VF) was defined as loss to follow-up, death or HIV-1 RNA viral load (VL) of >400 copies/mL at 6 months. When VL was >50 copies/mL, a genotypic resistance test was performed.
Results: Among the 97 children, median age at antiretroviral initiation was 31 months and the majority were in WHO clinical (77.3%) and immunological (70.1%) stage III or IV. At month 6, 44% of children had VL > 400 copies/mL (61% VF). Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). At failure, 6/8 children with wild-type viruses had a VL of <1000 copies/mL whereas 21/22 with resistant viruses had a VL of >1000 copies/mL.
Conclusions: Under NNRTI-based regimens, early detection of VF could allow the reinforcement of adherence when VL was <1000 copies/mL, because in most of these cases no resistance mutations were detected, or a change to a protease inhibitor-based regimen if VL was >1000 copies/mL. The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure.
Key Words: Africa , mutations , failure
These authors contributed equally to this work.