Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

Abstract

Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy.

Next generation sequencing reveals a high frequency of CXCR4 utilizing viruses in HIV-1 chronically infected drug experienced individuals in South Africa

“…However, in the current study, approximately 35% (23/66) of the patients infected with subtype C viruses harbored CXCR4 utilizing viruses and 57% (13/23) of these were X4 exclusively. The mechanism underling the emergence of X4 viruses in treatmentexperienced patients is not yet clear; and the question remains whether the identification of co-receptor switching and the emergence of drug resistance mutations are not coincidental events [35,36]. On the other hand, there is data showing that the up regulation of CCR5 is associated with HIV infection, and that this is reversed in the course of treatment [37,38].…”

HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4+ T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial

“…While in the ISS T-002 trial conducted in Italy patients were highly compliant to therapy, compliance was lower in the ISS T-003 study, a finding particularly frequent in Southern Africa where scarce adherence to cART therapy represents a relevant clinical problem since it is associated with disease progression, virus drug resistance and transmission [ 108 – 111 ]. Of interest, none of the vaccinees non-compliant to cART therapy experienced a decay of CD4 + T cells, and in most of them plasma viremia remained undetectable at week 48 while, in those with detectable viremia, viral load levels were low.…”

Structure-Guided Analysis of the Human APOBEC3-HIV Restrictome

“…Although the availability of antiretroviral therapies has significantly increased the life expectancy of those living with HIV/ AIDS, drug resistance compromises the effectiveness of current therapeutics (Ketseoglou et al, 2013;Kumar et al, 2014;Li et al, 2012;Masimba et al, 2013;Thiam et al, 2013). Additionally, many drug regimens currently employed to treat HIV/AIDS result in substantial side effects, such as lypodystrophy, hyperglycemia, liver failure, and cardiovascular diseases (Carr and Cooper, 2000;Kalayjian et al, 2012;Max and Sherer, 2000;Towner et al, 2012).…”