HIV Treatment Failure Markers; Virologic Outcomes after 12 Months of Antiretroviral Therapy among Patients Receiving HAART in Busia County, Kenya

Abstract

Data on virologic outcomes and the development of Human Immunodeficiency Virus (HIV) drug resistance in patients receiving antiretroviral therapy (ART) in resource-limited programmatic settings in sub-Saharan Africa is scanty. Thus, the need to describe the emergence of virologic failure and ART resistance patterns among patients treated with the standard highly active antiretroviral therapy regimens in these settings. The Kenyan Ministry of Health while collaborating with other stakeholders in the HIV field has been treating HIV infected patients in Busia County Referral Hospital, Western Kenya, since July 2003. While viral load testing as a marker of treatment failure is now routinely performed on patients on ART, HIV drug resistance testing (DRT) is not performed as a standard of care in majority of the testing facilities owing to the high cost and technical skill required to perform the test. The main objective of this cross-sectional study was to assess the effectiveness of ART in terms of virologic outcomes among patients receiving HAART for 12 months or more in Busia County Referral Hospital, Western Kenya. Blood samples from patients receiving first line therapy for >12 months at the hospital’s comprehensive care centre were collected and viral load testing performed. Samples with virologic failure (>1000 copies/ml) were genotyped to determine HIV drug resistance associated mutations (DRAMs) in the protease and reverse transcriptase (RT) regions of the HIV genome and HIV subtypes. Phylogenetic analysis was carried out using Molecular Evolutionary Genetics Analysis (MEGA) phylogenetic software version 11.0. The results showed a virologic failure of 15.9% (146/915 participants). Subtype A1 was the most predominant subtype (52.3%). Eighty-seven (62%) of participants with virologic failure had at least one major HIV DRAM against either the protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or a combination of two or more of the above and exhibited resistance against one or more antiretroviral drugs. Of these 87 participants with at least one DRAM, 65 (74.7%) were females while 22 (25.3%) were males. A total of 393 DRAMs against PIs, NNRTIs and NRTIs were identified in the study population as follows: PI DRAMs = 12, NNRTI DRAMs = 197 and NRTI DRAMs = 184. K103N/S was the most prevalent NNRTI DRAM while M184V was the predominant NRTI DRAM. Phenotypically, 39.3% of participants with virologic failure exhibited susceptibility to all tested ART drug classes. After phylogenetic analysis, the different subtypes clustered with reference sequences from around the globe with inter and intra-subtype cluster differences. This study concludes that HIV viral RNA quantification (viral load testing) may be used as a predictor of treatment failure in HIV seropositive patients receiving ART with 62.1% of those with virologic failure having one or more DRAMs that conferred resistance to one or more classes of drugs tested. The most predominant subtype circulating in the population is A1, with increased subtype D circulating recombinant forms (CRF) prevalence. Combination of viral load and drug resistance testing will find utility in better predicting treatment failure and assisting in making a decision on regimen change. This study recommends continued monitoring of the circulating subtypes, especially with the reported increase in CRFs and the mutation/resistance patterns to help predict treatment failure patterns, transmission rates, rates of recombination and disease progression within populations. Since not every treatment failure is associated with viral mutations, drug resistance testing should be provided to rule out adherence related treatment failure before any regimen switch is effected.