HIV-1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples

Abstract

BackgroundInfection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 pol and env genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully used in developed countries, these novel drugs are still limited in resource-poor countries. The aim of this study was to determine HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among Kenyan patients prior to widespread use of antiretroviral drugs.MethodsRemnant blood samples from consenting sexually transmitted infection (STI) patients in Nairobi were collected between February and May 2001 and stored. Polymerase chain reaction and cloning of portions of HIV-1 gag, pol and env genes was carried out followed by automated DNA sequencing.ResultsTwenty HIV-1 positive samples (from 11 females and 9 males) were analyzed. The average age of males (32.5 years) and females (26.5 years) was significantly different (p value < 0.0001). Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes: 12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant showing different subtypes in the three regions. Of 19 samples checked for co-receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4 variants being minor population.ConclusionHIV-1 subtype A accounted for majority of the infections. Though perceived to be a high risk population, the prevalence of recombination in this sample was low with no dual infections detected. Genotypic co-receptor analysis showed that most patients harbored viruses that are predicted to use CCR5.

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro

“…In addition, they are rarely observed in either drug naïve (<1%) or treatment-experienced patients (<5%) with preserved immunefunction (Brumme et al, 2005;Melby et al, 2006;Moyle et al, 2005;Wilkin et al, 2007;Simon et al, 2010). Conversely, a quite high proportion of patients harbouring dual/mixed-tropic viruses has been observed both in drug-naïve (prevalence ranging 12-15%) and in treatment-experienced patients (prevalence ranging 20-50%) (Church et al, 2008;Huang et al, 2007;Lihana et al, 2009;Moreno et al, 2009;Shepherd et al, 2008).…”

Drug Resistance Testing in HIV Infected Individuals on Treatment and Naive: Implications on Treatment Outcome

“…The presence of 3 of the following mutations M41L, D67N, L210W, T215Y/F, and K219Q/E has been associated with resistance to didanosin [6]. The presence of these mutations may improve subsequent virologic response to NNRTI-containing regimens (nevirapine or efavirenz) in NNRTI-naive individuals, although no clinical data exist for improved response to etravirine in NNRTI experienced individuals.…”

“…As ART use increases there is mounting evidence suggesting that DR will increase over time [6]. A recent cross-sectional study to determine treatment failure and drug resistance mutations among adults receiving first-line (3TC_d4T/AZT_NVP/EFV) and second-line (3TC/AZT/LPV/r) in Nairobi, Kenya, concluded that the detected accumulated resistance strains due to emergence of HIV drug resistance will continue to be a big challenge [7].…”

Analysis of Hiv Subtypes and Clinical Staging of Hiv Disease/Aids in East Java

“…Group M is divided into several subtypes, which until now has been recognized several subtypes, namely A1, A2, A3, A4, B, C, D, F1, F2, G, H, J, and K. 1 Between a subtype with other subtypes can form the so-called recombinant CRF (circulating Recombinant Form) and, until now, 43 CRF has been found. 2 Differences in the characteristics of subtypes of the virus and its interactions with the human host may influence the severity of the disease. Some studies proposed that the HIV subtype variation associated with the clinical stage of disease.…”