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Development of Drug Resistance in a Sub-Saharan Cohort of HIV 1-infected Adult Patients Receiving Fixed-dose Combination of Stavudine + Lamivudine + Nevirapine as Standard First-line Regimen
A G Marcelin1,2, A G Marcelin1,2, B Jarrousse3, M Ba4, M Dakouo5, A Doumbia6, I Haidara6, G Brucker1,2, G Brucker1,2, G Carcelain1,2, G Carcelain1,2, C Katlama1,2, C Katlama1,2, Vincent Calvez*1,2, Vincent Calvez*1,2, and SOLTHIS Triomune study group
1Ctr Hosp Univ Pitie-Salpetriere, Paris, France; 2SOLTHIS, Paris, France; 3SOLTHIS, Ségou, Mali; 4ONG Walé, Ségou, Mali; 5ONG APROFEM, Ségou, Mali; and 6Hosp Regional, Segou, Mali
Background: Generic fixed-dose combinations are largely used
in developing countries as first line regimen. As genotypic tests are not
widely available in these countries, it is important to characterize the
resistance patterns at failure with this kind of regimen in the perspective of
second line. We report our experience of stavudine (d4T;
30 mg) + lamivudine (3TC) + nevirapine
(NVP) in a program implemented by SOLTHIS in Ségou, Mali.
Methods: We included in the program 346 HIV-1-infected patients
who started d4T+3TC+NVP between January 2004 and August 2005. A virological substudy was
performed in 109 patients. HIV-1 plasma viral load was quantified after a
minimum of 6 months of HAART. In case of viral load >200 copies/mL, resistance genotype was performed.
Results: At baseline, 93% of patients had AIDS and
median CD4 count was 105 cells/mm3. Of the
109 patients, 83 (76%) had a viral load <200 copies/mL
at a median time of 6.7 months after initiation. Among the 26 patients with detectable
viral load (median viral load = 4150 copies/mL; range
209 to 404,000), viruses were not amplifiable in 4 cases. The 22 remaining patients harbored viruses with no mutation in 11 cases and resistance
mutations in 11 cases: 1 M184V alone, 10 M184V + non-nucleoside reverse
transcriptase inhibitor (NNRTI) mutations (6 Y181C, 2 K103N, 1 V106A, and 1
G190A). No thymidine analog
mutations (TAM) were observed. All sequenced viruses were CRF_02 subtype.
Conclusions: Early failures to d4T+3TC+NVP were associated
in 50% of cases with no resistance mutation. The fact that >50% of the viruses
harboring NNRTI mutations contained Y181C mutation in
this study could be related to the use of d4T. Actually, d4T would not prevent
the selection of Y181C mutation, inversely to that was observed in subtype B
when zidovudine (AZT) was associated to NVP. This
phenomenon can also be related to the CRF_02 subtype. It has been recently shown
that HIV-1 subtype can influences the type of NVP mutation (higher frequency of
Y181C for subtype A and K103N for subtype D). The absence of TAM suggests that AZT
or d4T could be used in second line regimen after early failure to d4T+3TC+NVP.
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