Characterization of drug resistance mutations in naïve and ART‐treated patients infected with HIV‐1 in Yaounde, Cameroon

Abstract

Currently the prevalence of HIV‐1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV‐1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV‐1 genetic diversity and to characterize HIV‐1 mutations conferring drug resistance among antiretroviral therapy (ART)‐naïve and ART‐treated patients. A cohort of 239 patients infected with HIV were followed‐up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV‐1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first‐line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second‐line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721–727, 2012. © 2012 Wiley Periodicals, Inc.

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.…”

“…Among the ART-naive patients, 18% and 15% harbored viruses with NRTI-associated mutations (M184V and T215Y/F) and viruses with NNRTI-associated mutations (K103N and Y181C), respectively. These prevalence rates are higher than the rates seen in earlier studies in Cameroon, which reported transmitted drug resistance rates in Cameroon ranging from 1.9% to 12.3% (1,11,23) in ART-naive patients. This increasing rate of transmitted HIVDR mutation is consistent with the increase in the availability of ARV in Cameroon over time.…”

“…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).…”

CLINICAL outcomes and loss to follow-up among people living with HIV participating in the NAMWEZA intervention in Dar es Salaam, Tanzania: a prospective cohort study

“…This level of drug adherence is very difficult to attain for PLH who are unable to sustain scheduled clinic follow-up visits, as studies indicate that the majority of patients with LTFU stop their ART. Stopping ART has been reported to quickly increase the risk of developing high serum viral load and other adverse health consequences [2, 5, 8, 9] including ART drug resistance, progression of HIV to AIDS, premature mortality, and re-infection, or infection of others with resistant strains [2–4, 10, 11]. …”

Phylogenetics of HIV-1 subtype G env: Greater complexity and older origins than previously reported

“…Cameroon is located in west central Africa, the epicentre of the HIV epidemic, where many HIV-1 types and subtypes co-circulate Tebit and Arts, 2011). Despite having a relatively low HIV prevalence, Cameroon has one of the most genetically diverse HIV epidemics in the world, with a very large variety of HIV-1 circulating recombinant forms (CRFs) Carr et al, 2010;Ceccarelli et al, 2012;Soares et al, 2010;Tongo et al, 2013;Torimiro et al, 2009). Subtypes CRF02_AG and G are among the most prevalent HIV-1 group M (HIV-1M) lineages in Cameroon Tongo et al, 2013) and in west Africa in general (Hemelaar et al, 2011).…”