Virological outcome and patterns of HIV‐1 drug resistance in patients with 36 months’ antiretroviral therapy experience in Cameroon

Abstract

IntroductionThe current expansion of antiretroviral treatment (ART) in the developing world without routine virological monitoring still raises concerns on the outcome of the strategy in terms of virological success and drug resistance burden. We assessed the virological outcome and drug resistance mutations in patients with 36 months’ ART experience, and monitored according to the WHO public health approach in Cameroon.MethodsWe consecutively recruited between 2008 and 2009 patients attending a national reference clinic in Yaoundé – Cameroon, for their routine medical visits at month 36±2. Observance data and treatment histories were extracted from medical records. Blood samples were collected for viral load (VL) testing and genotyping of drug resistance when HIV-1 RNA≥1000 copies/ml.ResultsOverall, 376 HIV-1 infected adults were recruited during the study period. All, but four who received PMTCT, were ART-naïve at treatment initiation, and 371/376 (98.7%) started on a first-line regimen that included 3TC +d4T/AZT+NVP/EFV. Sixty-six (17.6%) patients experienced virological failure (VL≥1000 copies/ml) and 53 carried a resistant virus, thus representing 81.5% (53/65) of the patients who failed. Forty-two out of 53 were resistant to nucleoside and non-nucleoside reverse-transcriptase inhibitors (NRTIs+NNRTIs), one to protease inhibitors (PI) and NNRTIs, two to NRTIs only and eight to NNRTIs only. Among patients with NRTI resistance, 18/44 (40.9%) carried Thymidine Analog Mutations (TAMs), and 13/44 (29.5%) accumulated at least three NRTI resistance mutations. Observed NNRTI resistance mutations affected drugs of the regimen, essentially nevirapine and efavirenz, but several patients (10/51, 19.6%) accumulated mutations that may have compromised etravirine use.ConclusionsWe observed a moderate level of virological failure after 36 months of treatment, but a high proportion of patients who failed developed drug resistance. Although we found that for the majority of patients, second-line regimens recommended in Cameroon would be still effective, accumulated resistance mutations are of concern and may compromise future treatment strategies, stressing the need for virological monitoring in resource-limited settings.

Use of Amplification Refractory Mutation System PCR Assay as a Simple and Effective Tool To Detect HIV-1 Drug Resistance Mutations

“…These findings are consistent with previous studies that have reported similar rates of acquired drug resistance mutations in Cameroon (8,23) and other African countries with similar ART programs (10,31,32). The most prevalent mutations identified were M184V and K103N.…”

“…Using the aforementioned criteria, M184V and T215Y/F were selected as nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, while K103N and Y181C were selected as non-NRTI (NNRTI). M184V is the most common (37% to 90%) of the NRTI resistance mutations causing high-level resistance to lamivudine (3TC) and (8,22,23). The drugs affected (FTC, 3TC, AZT, ABC, EFV, and NVP) are among those most commonly used in the regimens recommended by WHO guidelines for first-line treatment in resource-constrained countries, especially in sub-Saharan Africa (6).…”

“…In addition to these challenges, the low genetic barrier of commonly used antiretrovirals (ARV) for first-line treatment further increases the risks of HIVDR mutations. The most prevalent mutations that cause intermediate-to high-level resistance to this first-line regimen in countries such as those in the central African region, including Cameroon, Central African Republic, Gabon, etc., that use the WHO approach are M184V (37% to 90%), T215Y/F (11% to 47.2%), K103N (14% to 44%), and Y181C (9.4% to 19.8%) (8)(9)(10)(11)(12)(13). These can restrict treatment options and increase cost by requiring new and more expensive ARV regimens (36).…”

The Prediction of Integrase Inhibitors Efficacy in Third Line Regimen after First and Second Line Antiretroviral Therapy Failure in Senegal

“…Similar results have been reported in Cameroon [22,23], in Republic of Central Africa [24] and in Republic of South Africa [25]. These observations show an importance to better manage patients undergoing ART by physicians for an earlier suppression of VL.…”

HIV Drug Resistance and Phylogeny Profile in Naïve and Antiretroviral-Experienced Patients in Tehran, Iran

“…The therapy has dramatically decreased morbidity and mortality rates in patients with HIV-1 infection in both developed and less affluent countries [3,4]. However, incomplete viral suppression results in the spread of HIV-1 resistance to the drugs, which not only jeopardizes therapeutic effects for individuals, but also puts the entire global population at risk [5,6].…”