Abstract
BackgroundIt remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART).MethodsWe recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models.Results54 patients with previously assigned HIV-1 subtypes (24 CRF01_AE, 17 B, 8 B', 1 CRF33_01B, 3 CRF34_01B and 1 G) were observed for 89 patient-years. Subtype CRF01_AE and non-CRF01_AE infected patients did not differ in age, gender, risk factor, rate of symptomatic seroconversion, baseline CD4+ T-cell count, log10 viral load or haemoglobin concentration. The estimated annual rate of CD4+ T-cell loss was 58 cells/mm3/year (95% CI: 7 to 109; P = 0.027) greater in subtype CRF01_AE infected patients compared to non-CRF01_AE patients, after adjusting for age, baseline CD4+ T-cell count and baseline log10 viral load. The median time from EDS to ART was 1.8 years faster comparing CRF01_AE to non-CRF01_AE infected patient with a 2.5 times (95% CI: 1.2-5.0; P = 0.013) higher hazard for ART initiation, after controlling for age, baseline CD4+ T-cell count and baseline log10 viral load.ConclusionsInfecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis.
Highlights
The global HIV-1 pandemic is characterized by extensive genetic diversity [1]
The primary objective of our study was to determine the difference between subtype CRF01_AE and other circulating subtypes in the pre-antiretroviral therapy (ART) annual rate of CD4 decline in subjects with known dates of seroconversion
We examined the time from infection to ART initiation by infecting subtype
Summary
Uncertainty exists as to whether different subtypes manifest different pathogenicity, and by implication different host-pathogen interactions [2]. Genotypic differences in viral pathogenicity have implications in determining viral genotypic motifs important to disease progression, vaccine development and disease transmission [3]. Clinical guidelines may have to be subtype-specific if significant differences exist [4,5]. The overwhelming majority of data on HIV-1 is based on subtype B, the predominant subtype in developed countries. Subtype B accounts for only 10% of infections worldwide [2]. It remains controversial as to whether HIV-1 subtypes influence disease progression. We compared subtype CRF01_AE and nonCRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART)
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