Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.
BACKGROUND
The HIV-1 epidemic in African countries is largely due to non-B HIV-1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates.


METHODS
HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first-line therapy (plasma HIV RNA >1000 copies/mL). Sequence analysis of the reverse transcriptase and protease gene revealed drug resistance mutations and HIV-1 viral subtype. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation.


RESULTS
Since 2005, 338 patients were evaluated. The most prevalent subtypes were CRF02_AG [152 of 338 (44.9%)] and G [128 of 338 (37.9%)]. Three hundred seven of 338 (90.8%) patients had previously received stavudine and/or zidovudine + lamivudine + efavirenz or nevirapine; 41 of 338 (12.1%) had received tenofovir (TDF). The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). The K65R mutation was present in 37 of 338 patients (10.9%). The Q151M (P < 0.05), K219R, and T69del (P < 0.01) mutations were more common in patients with K65R who had not received TDF.


CONCLUSIONS
The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes, whether or not they have been exposed to TDF.
Hawkins
Claudia A
CA
Northwestern University, Chicago, IL 60611, USA. c-hawkins@md.northwestern.edu
Chaplin
Beth
B
Idoko
John
J
Ekong
Ernest
E
Adewole
Isaac
I
Gashau
Wadzani
W
Murphy
Robert L
RL
Kanki
Phyllis
P
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009549:Nigeria; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D055815:Young Adult
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1