[O7] THE IMPACT OF BASELINE POLYMORPHISMS IN REVERSE TRANSCRIPTASE AND PROTEASE ON THE OUTCOME OF HAART IN HIV-1 INFECTED AFRICAN PATIENTS

7th Annual Conference Of The British HIV Association [BHIVA]

27 – 29 April 2001, The Hove Centre, Brighton

[TITLE:] THE IMPACT OF BASELINE POLYMORPHISMS IN REVERSE TRANSCRIPTASE AND PROTEASE ON THE OUTCOME OF HAART IN HIV-1 INFECTED AFRICAN PATIENTS

[AUTHOR(S):] AJ Frater¹, A Beardall¹, K Ariyoshi², D Churchill¹, S Galpin¹, JR Clarke¹, MO McClure¹, JN Weber¹
¹ Jefferiss Trust Laboratories, Wright-Fleming Institute, Imperial College School of Medicine, St Mary's Hospital, London, UK, and ² AIDS Research Centre, National Institute of Infectious Diseases, Tokyo, Japan

BHIVA Conf 2001 Apr 27-29;7:O7

BACKGROUND: The clinical response to highly active antiretroviral therapy (HAART) of patients infected with African HIV-1 subtypes is poorly documented. We studied a cohort of African patients to assess therapeutic response and investigate the significance of polymorphic codons.

METHODS: African patients on HAART were identified from the St Mary's Hospital HIV database. Clinical outcome was assessed using viral load and CD4 counts. Pre- and post-therapy sequences of reverse transcriptase (RT) and protease were obtained using the ABI Viroseq genotyping kit. The impact of subtype and polymorphisms on outcome was assessed statistically, phylogenetically and by d_s/d_n ratios.

RESULTS: 79 treatment-naïve African patients commenced HAART; 60/79 had an undetectable viral load for 1 year, with no differences according to regimen; 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 affected the clinical outcome. Sequences from patients experiencing viral rebound produced a non-significant change in the d_s/d_n ratios from baseline, suggesting only weak drug pressure.

CONCLUSIONS: The response of patients infected with African subtypes of HIV-1 to HAART appears to be independent of regimen, 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.

PRESENTING AUTHOR: AJ Frater

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