Hiv-1 Drug Resistance Profiles of Ghanaian Women on Antiretroviral Therapy After Prevention of Mother-To-Child Transmission (Pmtct)

Abstract

From 2007 to 2011 HIV-positive pregnant women in Ghana, were given a combination of Zidovudine and Lamivudine as prophylaxis during pregnancy and a single dose of Nevirapine upon the onset of labour towards the prevention of mother to child transmission (PMTCT) of HIV. Since these women were subsequently given the same antiretrovirals (ARVs) to manage their HIV infection, there was therefore the need to determine the HIV-1 drug resistance profiles in such patients in Ghana. This study sought to investigate HIV-1 drug resistance associated mutations present in mothers on ART who had previously received ART prophylaxis for PMTCT in selected centres in Ghana. Genotypic Drug Resistance Testing for HIV-1 was carried out on study participants to identify any HIV-1 drug resistance associated mutations present and HIV viral load and CD4 counts were also measured. There were three categories of HIV-1 patients encountered in this study- Concordant Responders (had increased CD4 with viral suppression to undetectable levels), Immunological Responders (had increased CD4 but with detectable viremia) and Immunological Non-Responders (had decreased CD4 with viral suppression to undetectable levels). Participants who had prophylaxis before HAART, those who had HAART without prophylaxis and the drug-naïve participants had 32% (8), 5% (3) and 15% (4) HIV-1 drug resistance associated mutations (DRAMs) respectively.

Thirty-five percent (35%) had nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations(RAMs) in the RT gene and 1 (3%) had RAMs in the PR gene for PIs. The most common NRTI mutation found was M184V; K103N and A98G were the most common NNRTI mutation found in this study. Thymidine Analogue Mutations (TAMs) such as M41L, D67N, K70R, L210W, T215Y/F and K219E were found in all the groups; the most common of the TAMs found in the study is M41L and T215Y. The major resistance mutation to Protease Inhibitors (PIs) seen in the study was I84V. Two HIV-1 drug-naïve patients in the Eastern region had mutations that conferred resistance to both nucleoside reverse transcriptase inhibitors (M184V and L210W) and non-nucleoside reverse transcriptase inhibitors (K103N and V106A). For the Reverse Transcriptase gene, 33(83%) of samples were of subtypes CRF02_AG, 2(5%) were subtype CRF01_AE, 1(3%) was subtype A, 2 (5%) were subtype B and 2 (5%) were subtype G. With the Protease gene, 32 samples (97%) were subtype CRF02_AG and 1(3%) was subtype A. HIV-1 positive Ghanaian mothers who had prophylaxis prior to initiating ART had immunological, virological and HIV-1 drug resistance associated mutations profiles that have adverse effect on their clinical profiles, resulting in sub-optimal responses to ART. Emergence of transmitted HIV-1 drug resistance could be on the increase and needs to be monitored. Drug resistance testing and early initiation of treatment upon diagnosis would help to produce a better treatment outcome for Ghanaian HIV-1 positive mothers and pregnant women. The study has provided useful baseline information on the profiles of Ghanaian women on ART after prophylaxis.