Impact of baseline polymorphisms in RT and protease on outcome of highly active antiretroviral therapy in HIV-1-infected African patients.
OBJECTIVE
To assess the therapeutic response and investigate the significance of polymorphic codons in African patients receiving highly-active antiretroviral therapy (HAART).


METHODS
African patients were identified from the St Mary's Hospital HIV-1 database. Clinical outcome was assessed by viral load and CD4 cell count. Pre- and post-therapy sequences of RT and protease were analysed. The impact of subtype and individual polymorphic codons on therapeutic outcome was assessed statistically (Fishers exact and chi2 tests) and phylogenetically (Jukes and Cantor).


RESULTS
Of 79 drug-naive African patients who were prescribed HAART, 60 remained undetectable for 1 year, with no differences detected in the clinical response to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-containing regimes. Country of origin, sex and viral subtype had no impact on outcome of HAART. A total of 133 polymorphisms were identified in pol (37 in protease and 96 in RT), with a mean of 9.0 in protease and 22.3 in RT per patient. There was no significant difference in the overall numbers of polymorphisms per patient, and no single polymorphism had any impact on clinical outcome. Sequences from 'failing' patients experiencing viral rebound produced few mutations known to be associated with drug resistance, suggesting minimal drug pressure.


CONCLUSIONS
The response of patients infected with African subtypes of HIV-1 to HAART appears to be independent of regime, HIV-1 clade and baseline polymorphisms. Non-B subtypes are fully sensitive to HAART and, accordingly, therapy should not be withheld from African patients for reasons of viral diversity.
Frater
A J
AJ
Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Imperial College School of Medicine, St Mary's Hospital, London, UK.
Beardall
A
A
Ariyoshi
K
K
Churchill
D
D
Galpin
S
S
Clarke
J R
JR
Weber
J N
JN
McClure
M O
MO
D000349:Africa; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D019562:Viral Load
D054303:HIV Reverse Transcriptase; D016333:HIV Protease