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Influence of Genotypic Drug-resistance Mutation on Clinical and Immunological Outcomes in HIV-infected Adults Receiving ART in Abidjan, Côte d’Ivoire
Catherine Seyler*1,2, Catherine Seyler*1,2, C Adjé-Touré3, N Dakoury-Dogbo2, D Gabillard1, E Messou2, S Touré2, F Rouet4, R Marlink5, M Nolan3, X Anglaret1,2, and X Anglaret1,2
1INSERM U593, Univ Victor Segalen, Bordeaux, France; 2PACCI and ACONDA, Abidjan, Côte d'Ivoire; 3Project RETRO-CI, Abidjan, Côte d'Ivoire; 4CeDReS, Ctr Hosp Univ de Treichville, Abidjan, Côte d'Ivoire; and 5Elizabeth Glaser Pediatric AIDS Fndn, Santa Monica, CA, US
Background: In sub-Saharan Africa, outcomes on HAART in
patients with HIV-1 antiretroviral drug resistance mutations has never been
reported.
Methods: In July 2004 in one HIV care center
of Abidjan, adults on HAART had plasma HIV-1 RNA measurement (real time polymerase
chain reaction [RT-PCR], detectability 300 copies/mL). Patients with detectable
viral load had resistance genotypic test. Patients were followed until March
2006, under standardized cohort procedures. Main outcomes were serious
morbidity (WHO stage 3-4 classifying, or leading to hospitalisation or death)
and immunological failure (CD4 <200/mm3). Cox multivariate model
was used to analyse factors associated with outcomes.
Results: We recruited 106 adults (women 59%, median age
38 years, median CD4 nadir 122/mm3). At study entry, 54% and 44% of
them were receiving 2 nucleoside reverse transcriptase inhibitors (NRTI) + 1
protease inhibitor (PI) and 2 NRTI +1 non-NRTI (NNRTI), respectively; the
median previous time on HAART was 37 months (IQR 27 to 48) and the median CD4
count 266/mm3 (159 to 407); 62 (58%) patients had undetectable viral
load, 21 (20%) detectable viral load with no major resistance mutation, and 23
(22%) detectable viral load with ≥1 major resistance mutation. (M184V
n = 15, D67N n =
6, M41L n = 6, K103N n = 10, and L90M n = 2 ). Patients
were then followed-up a median of 20 months, 1 patient was lost to follow-up
and 1 died. The 18-month probability of remaining alive and free of serious
morbidity was 0.79 in
patients with undetectable viral load at study entry, versus 0.86
in those with detectable viral load without mutation (p = 0.90) and 0.69 in those with
resistance mutation (p = 0.19). At
study termination, 22 (20%) patients had <200 CD4/mm3. Factors
associated with immunological failure were: low baseline CD4 count (p = 0.007) and ≥1 resistance mutations at study entry (p = 0.04). Compared with patients with
undetectable viral load, those with detectable viral load without mutation and
those with ≥1 mutations had adjusted hazard ratios of immunological
failure of 2.56 (0.76-8.54) and 4.32 (95%CI 1.38 to 13.57), respectively. In
patients with undetectable viral load, detectable viral load without mutation
and with mutation, the median change in CD4 count between study entry and study
termination was +129/mm3 (+19; +210), +51/mm3 (–14; +123),
and +3 /mm3 IQR (–15; +61), respectively.
Conclusions: Among these sub-Saharan African adults on
HAART, patients with major resistance mutation had higher rate of immunological
failure and tented to have higher rate of serious morbidity, but their CD4
count remain stable within the following 18 months and only 1 of them died.
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