The epidemiology and clinical correlates of HIV‐1 co‐receptor tropism in non‐subtype B infections from India, Uganda and South Africa

Quazi Ataher,Sybil Eng,Anna Greenacre,Simon Portsmouth,Laura A Napolitano,Sharlaa Badal‐Faesen,Andrew Kambugu,Robin Wood,Randy Tressler

doi:10.1186/1758-2652-15-2

Abstract

BackgroundThe introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. This study was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.MethodsHIV-1-infected patients were recruited into this prospective, cross-sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV-1 subtype and co-receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4+ and CD8+ T cell counts.ResultsCCR5-tropic (R5) HIV-1 was detected in 96% of treatment-naïve (TN) and treatment-experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed-tropic HIV-1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4+ count.ConclusionsR5 HIV-1 was predominant in TN individuals with HIV-1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4+ count correlated with R5 prevalence, while treatment experience was associated with increased non-R5 infection in all subtypes.

Highlights

The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different Human immunodeficiency virus type-1 (HIV-1) subtypes and geographical locations
The aim of this study was to estimate the prevalence of Results: CCR5-tropic (R5), D/M, and X4-tropic HIV-1 among isolates obtained from patients with HIV-1 subtype C infection from India and South Africa, and with subtype A/A1 and D infection from Uganda, and to explore the demographic and clinical characteristics associated with R5 infection
This study examined the correlates of HIV-1 co-receptor tropism in virus from individuals with non-B subtype HIV-1 infection from India, Uganda and South Africa

Summary

Introduction

The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. Studies of HIV-1 co-receptor tropism, which have been conducted primarily in populations where subtype B infections predominate, have demonstrated a relationship between HIV-1 co-receptor use and disease stage. Early stages of infection and disease are characterized by greater prevalence of only C-C chemokine type 5 (CCR5)-tropic (R5) HIV-1, which has been associated with slower progression to AIDS [8,9,10,11,12]. The emergence of C-X-C chemokine receptor type 4 (CXCR4)-using virus (X4) has been associated with greater treatment experience and higher risk of death, and coincides with more rapid CD4+ T-cell depletion and disease progression [6,8,9,12,13]. 50% of patients who die of HIV-1 disease have only R5 HIV-1 detectable at the time of their death, indicating that CCR5 remains a critical co-receptor throughout the course of HIV infection [12,15]

Objectives

Methods

Results

Discussion

Conclusion