Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya

Abstract

Access to antiretroviral therapy (ART) is increasing in resource-limited settings (RLS) and can successfully reduce HIV-related morbidity and mortality. However, virologic failure and development of viral drug resistance can result in reduced treatment options and disease progression. Additionally, transmission of resistant virus, and particularly multi-drug resistance, could become a public health concern. This study evaluated treatment success and development of ART drug resistance after short-term treatment among patients attending the Comprehensive HIV Care Centre (CCC) of Coast Province General Hospital, Mombasa, Kenya. One hundred and fifty HIV-infected individuals receiving ART were consecutively recruited to participate in the study. After determination of plasma viral load, patients with detectable viral load levels were subjected to genotypic drug resistance testing. At the time of sampling, 132 of the 150 participants were on ART for more than 6 months (median 21 months, IQR = 12-26). An efficient viral load reduction to below 50 copies/ml was observed in 113 (85.6%) of them. Of the 19 patients with a detectable viral load, sequencing of the protease (PR) and reverse transcriptase (RT) gene was successful in 16. Eleven (11) of these 16 patients were infected with a subtype A1 virus. Major PR mutations were absent, but mutations associated with drug resistance in RT were detected in 14 of the 16 patients (87.5%). High-level resistance against at least 2 drugs of the ART regimen was observed in 9/14 (64.3%). The 3TC mutation M184V and the NNRTI mutation K103N were most frequent but also the multi-drug resistance Q151M and the broad NRTI cross-resistance K65R were observed. The results of this study revealed a high rate of treatment success after short term ART in patients treated at a public provincial hospital in a RLS. Nevertheless, the observed high risk of accumulation of resistance mutations among patients failing treatment and the selection of multi-drug resistance mutations in some, remains of great concern for future treatment options and potential transmission to partners.

Field Evaluation of a Broadly Sensitive HIV-1 In-House Genotyping Assay for Use with both Plasma and Dried Blood Spot Specimens in a Resource-Limited Country

“…Agreement was interpreted as weak (0.400 Ͼ Ն 0.200), moderate (0.600 Ͼ Ն 0.400), strong (0.800 Ͼ Ն 0.600), nearly perfect (1.00 Ͼ Ն 0.800), and perfect ( ϭ 1.000). Sample size was estimated using Buderer's formula (38) with the following assumptions: HIVDR prevalence of 9.3% based on a previous study in Kenya (39), anticipated sensitivity equivalent to that obtained with the ViroSeq system of 99.65 (35), and a two-sided test with an alpha value of 0.05 and a precision value of 0.05. A minimum sample size of 60 was then required in order to obtain a sensitivity equivalent to that of the ViroSeq system.…”

Seroprevalence and Risk Factors Associated with Measles outbreaks among Children in Kwale, Lamu and Narok Counties in Kenya, 2014

“…Nevertheless, the county benefited from a measles mop-up immunisation programme supplemented with vitamin A given to children aged between 9 and 59 months. This Campaign was conducted between 3 rd and 7 th November 2012 and covered approximately 92.0% of the target population [12]. Narok County: A part of the study participants were drawn from Narok County.…”

“…Despite the reported high measles immunisation coverage of 85% -90% that followed, in 2012, repeat outbreaks occurred that comprised 3,056 cases of which 767 were confirmed, an increase of 102 confirmed cases from 2011 outbreaks [9,10]. This prompted a massive immunisation programme that covered more than 99% of the target population (9 -59 months old children) [11][12][13]. Genetic characterisation of measles virus has revealed 24 genotypes distributed within 8 genotypic groups as; A, B1-3, C1-2, D1-11, E, F, G1-3, and H1-2 [14].…”

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

“…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]. Another study carried out to evaluate treatment success and development of ART drug resistance at the Coast Province General Hospital, Mombasa, Kenya, revealed a high rate of treatment success after short term ART in patients treated at a public provincial hospital detected minority complex drug resistance profiles that were predictive of resistance to currently used second-line NRTIs and NNRTIs regimens [1]. In this article we present detailed data on DRMS from patients who had not started ARV and those who were failing with their implications on therapy.…”

“…Development of HIV drug resistance is inevitable in patients on ART. Increase in antiretroviral therapy (ART) in resource-limited settings (RLS) will successfully reduce HIV-related morbidity and mortality [1]. The increase in ART coverage is expected to lead to an increase in drug-resistant strains among experienced patients.…”