Multiple HIV-1 subtype infection and transmitted drug resistance; prevalence in HIV-1 infected Ugandans and association to disease stage and progression

Abstract

Infection of an individual with two or more viral strains (dual/mixed infection) occurs in HIV-1 infection. The identification of the immunological and virological determinants of dual infection would provide data that is relevant for vaccine design and development. The primary objective of this study was to determine the prevalence of dual infection in low risk and high-risk sexual behavior populations in Uganda. From these two populations, the following was done: 1) determined the prevalence of dual infection; 2) determined the clinical consequences of dual infection; 3) determined the course of HIV-1 recombination following dual infection; 4) determined the prevalence of HIV-1 transmitted drug resistance (TDR) among recently infected individuals. Dual infection was determined by sequencing of the env-C2V3, gag-p24, gp41 and pol-IN genes. The rate of disease progression was compared between singly and dually infected individuals using Cox regression. To screen for TDR, the polymerase (pol) gene was sequenced and the presence of TDR was scored using the 2009 World Health Organization (WHO) mutation list. In the low risk population, 35 individuals were fully analyzed; the subtype distribution was 48.6% (n=17) A/D recombinants, 28.6% (n=10) D, 17.1% (n=6) A and 5.7% (n=2) C. In the high-risk population, among 210 women showed subtype A 54.3% (n=114), subtype D (24.3%, n=51), recombinants (18.6%, n=39) and C (2.9%, n=6). In the low risk population the prevalence of dual infection was 14.3% (5/35) compared to 9.3% (5/54) in the high-risk population. The rate of disease progression was significantly higher amongst dually infected individuals compared to singly infected individuals (hazard ratio 3.35; 95% CI 1.09, 10.3; p = 0.049). The emergence of recombinant viruses was identified in two dually infected individuals. The prevalence of TDR was 2.6% (one out of 38 women fully analyzed). In conclusion, since dual infection has been shown to lead to faster disease progression and increase in HIV-1 diversity through recombination, it remains important for health care providers to put in place measures to prevent dual infection. The observed low prevalence of TDR could be an indicator that the national antiretroviral therapy programs are effective. This study therefore provided an important framework for future work on identifying the immunological and virological factors that allow or permit HIV-1 infected individuals from acquiring more strains; data that could be useful for vaccine design and development and patient care.