Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting.
OBJECTIVE
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/mm(3). 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).


CONCLUSIONS
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.
Unité d'Epidémiologie Moléculaire de la Résistance du VIH aux ARV, SEREFO, FMPOS, University of Sciences Techniques and Technologies of Bamako - USTTB, BP: 1805, Bamako, Mali. amaiga@icermali.org
Almoustapha Issiaka
AI
Maiga
Djeneba Bocar
DB
Fofana
Mamadou
M
Cisse
Fodié
F
Diallo
Moussa Youssoufa
MY
Maiga
Hamar Alassane
HA
Traore
Issouf Alassane
IA
Maiga
Aliou
A
Sylla
Dionke
D
Fofana
Babafemi
B
Taiwo
Robert
R
Murphy
Christine
C
Katlama
Anatole
A
Tounkara
Vincent
V
Calvez
Anne-Geneviève
AG
Marcelin
D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D016903:Drug Monitoring; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008302:Mali; D008875:Middle Aged; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents