Abstract
BackgroundOur intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London.MethodsA random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression.ResultsComplete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01)ConclusionsThis is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.
Highlights
The world-wide HIV epidemic has been characterized by increasing genetic diversity, with multiple distinct viral subtypes, as well as sub-subtypes, and circulating recombinant forms (CRFs) [1,2,3]
The main objectives of our study were to compare the rate of disease progression, based on rate of CD4 decline prior to antiretroviral therapy (ART), and the initial and subsequent virological response to ART in an ethnically diverse population in south London infected with subtype B and the most common non-B HIV-1 subtypes (A, C, D and CRF02AG)
Characteristics of 679 patients infected with B and non-B subtypes, A, C, D, and CRF02-AG Of 861 patients, 182 patients were excluded from the analysis because their subtype could not be determined due to mixed reactivity or non reactivity (n = 109); unspecified non-B subtype (n = 16); less common non-B subtypes (n = 34); and incomplete epidemiological data (n = 23, 13 B, 4 A, and 6 C)
Summary
The world-wide HIV epidemic has been characterized by increasing genetic diversity, with multiple distinct viral subtypes, as well as sub-subtypes, and circulating recombinant forms (CRFs) [1,2,3]. Subtype B dominates in North America, western Europe and Australia, the recent epidemiology of HIV-1 infection in the UK and many western European countries has been characterized by a marked increase in the prevalence of non-B subtypes and several CRFs [4,5,6,7,8,9]. Our intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London
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