TY - JOUR
T1 - Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting
AU - Maiga, Almoustapha Issiaka
AU - Fofana, Djeneba Bocar
AU - Cisse, Mamadou
AU - Diallo, Fodié
AU - Maiga, Moussa Youssoufa
AU - Traore, Hamar Alassane
AU - Maiga, Issouf Alassane
AU - Sylla, Aliou
AU - Fofana, Dionke
AU - Taiwo, Babafemi
AU - Murphy, Robert
AU - Katlama, Christine
AU - Tounkara, Anatole
AU - Calvez, Vincent
AU - Marcelin, Anne Geneviève
N1 - Funding Information:
This study was funded by ESTHER (Ensemble pour une Solidarité Hospita-lière en Réseau) in Mali; the National AIDS Program in Mali (CSLS/MS), SOLTHIS (Solidarité Thérapeutique Hospitalière et Initiative contre le Sida) in Mali, ANRS (Agence Nationale de Recherche sur le SIDA) and The Northwestern University-United States National Institutes for Health/Fogarty International Center grant D43TW007995.
PY - 2012/12
Y1 - 2012/12
N2 - Objectives: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.
AB - Objectives: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.
KW - Africa
KW - Resistance
KW - Third-line
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U2 - 10.1093/jac/dks310
DO - 10.1093/jac/dks310
M3 - Article
C2 - 22888273
AN - SCOPUS:84869391319
SN - 0305-7453
VL - 67
SP - 2943
EP - 2948
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 12
M1 - dks310
ER -
