High level of primary drug resistance in Mali.
BACKGROUND
As access to antiretroviral drugs increases in developing countries, it will become increasingly important to monitor the emergence of resistance and to define the molecular pathways involved to identify optimal therapeutic regimens.


METHODS
We performed genotypic resistance testing on plasma obtained from 101 HIV-infected treatment-naïve individuals from Mali. Genotyping was carried out using the Virco protocols and HXB2 was used as the reference strain.


RESULTS
CRF02_AG was the most common subtype, present in 71.3% of our patient population. Other subtypes included B, C, G, CRF06_CPX, CRF09_CPX, CRF01_AE, A2/CRF16_A2D, A1 and CRF13_CPX. A total of 9.9% [95% confidence interval (CI) 6.9-12.9%] of patients had at least one resistance mutation. The prevalences of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 5% (95% CI 0.7-9.2%), 6% (95% CI 1.3-10.6%) and 0%, respectively. The most frequent mutations were T215A/Y for NRTIs and K103N/T for NNRTIs. One patient harboured three NRTI resistance mutations and one NNRTI mutation. This is the first reported case of multi-drug-resistant viral transmission in Mali. Polymorphisms at protease codons 10I/V and 33F potentially associated with resistance were observed in 18.8% and 1% of patients, respectively. Several polymorphisms in the C-terminal domain of reverse transcriptase were observed: A371V (in 63.4% of patients), G335D (76.2%), E399D (10.9%) and G333E (1%).


CONCLUSIONS
Primary resistance was seen in 9.9% of subjects, which is higher than previously reported in Mali. Taking into consideration other polymorphisms in protease such as L10I/V and 33F, primary resistance could reach 28.7% (95% CI 19.9-37.5%). Our study reflects the need to monitor the evolution of resistance on a regular basis and trends of transmitted resistance.
Haidara
A
A
Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Canada.
Chamberland
A
A
Sylla
M
M
Aboubacrine
S A
SA
Cissé
M
M
Traore
H A
HA
Maiga
M Y
MY
Tounkara
A
A
Nguyen
V K
VK
Tremblay
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008302:Mali / Q000453:epidemiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D055815:Young Adult
D019380:Anti-HIV Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase