Pattern of HIV-1 Drug Resistance among Adults on ART in Nigeria

Abstract

Background:The development of anitiretroviral drug resistance may limit the benefit of antiretroviral therapy. Therefore the need to closely monitor these mutations, especially the use of ART is increasing. This study was therefore designed to determine the ARV drug resistance pattern among ART naïve and expose individuals attending a PEPFAR supported by antiretroviral clinic in Nigeria. Methodology: The study participants included patients attending the PEPFAR supported by University College Hospital (UCH), Ibadan ART clinic who have been on HIV treatment for at least one year with consecutive viral load of over 2000 copies/ml as well some ART Naïve individuals with high (>50,000 copies/ml) baseline viral level attending the hospital for pre-ART assessment. Blood sample was collected from each individual for CD4 enumeration, viral load level determination and DNA sequencing for genotypic typing. Antiretroviral drug resistance mutations (DRM) were determined by using the Viroseq software and drug mutations generated by using a combination of Viroseq and Stanford algorithm. DRM were classified as major or minor mutations based on the June 2013 Stanford DR database. Results: The most common major NRTI, NNRTI and PI mutation were D67N (33.3%), Y181C (16.7%) and M46L/I (55.6%) respectively. Lamivudine (3TC) and emtricitabine (FTC); nevirapine (NVP) and nelfinavir (NFV) were the most common NRTI, NNRTI, and PI drugs to which the virus in the infected individuals developed resistance. Isolates from 4 patients were resistant to triple drug class, including at least one NRTI, NNRTI and a PI. Only one (4.8%) of the isolates from drug Naïve individuals had major DRM that conferred resistance to any drug. Conclusion: Demonstration of high rates of antiretroviral DRM among patients on 1 st and 2 nd line ART and the presence of DRM in drug Naïve individuals in this study show the importance of surveillance for resistance to ARV in line with the magnitude of scaling up of treatment program in the country.

Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria

“…This mutation which occurred at a frequency of 7.14% among all the isolates and frequency of 16.7% among the subtype G isolates accounted for over 66.0% of all the major PI resistance mutations identified in this study. Again, this is also similar to the report of Odaibo et al [17] which reported this mutation at a frequency of 55.6%. Although our study did not determine the phenotypic resistance pattern in the infected individuals (a limitation of the study), analysis according to the Stanford algorithm showed that M46L mutation confers potential low-level resistance to ATV/r, FPV/r, IDV/r, LPV/r, TPV/r and intermediate-level resistance to NFV to isolates in this study as shown in Table 3.…”

“…The frequency of occurrence (10.7%) of major PI resistance mutations, M46L and V82L, obtained in this study is somewhat lower than the 39.1% recorded in a similar study conducted by Odaibo et al [17] on pattern of HIV-1 drug resistance among adults on ART in Nigeria. However, some other studies conducted in different parts of the country on both drug naïve and experienced patients reported no major PI resistance mutations [18,19].…”

“…V82L is an uncommon non-polymorphic substratecleft mutation known to reduce susceptibility to TPV. This mutation was reported at a frequency of 22.2% in a similar study by Odaibo et al [17].…”

“…There is however comparatively little available data from less developed countries where non-B subtypes predominate. In Nigeria where the epidemic is largely driven by non-B subtypes, reports on HIV drug resistance and polymorphisms [12][13][14][15][16][17][18][19][20][21] have primarily focused on resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) while resistance to Protease inhibitors (PI) remain understudied. Since the commencement of ART program in Nigeria in 2001, government has collaborated with some donor agencies such as Global Fund to Fight AIDS, Tuberculosis, and Malaria and US President's Emergency Plan for AIDS Relief (PEPFAR) to scale up its ART clinics.…”

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

“…NRTI resistance was also common, led by the M184V mutation. The predominance of these two mutations is consistent with several previous reports in Nigeria [11,14,15], whereas other studies noted a stronger predominance of Y181C [13,16,18]. Although the prevalence of NNRTI DRMs in our sample supports the move to dolutegravir-based combinations as first-line ART in Nigeria, resistance to NRTIs may still threaten initial treatment regimens.…”