Research Article: HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013

Date Published: October 10, 2018

Publisher: Public Library of Science

Author(s): Dawit Assefa Arimide, Almaz Abebe, Yenew Kebede, Fekadu Adugna, Tesfaye Tilahun, Desta Kassa, Yibeltal Assefa, Taye Tolera Balcha, Per Björkman, Patrik Medstrand, Jason Blackard.

http://doi.org/10.1371/journal.pone.0205446

Abstract

The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C’-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country.

A cross-sectional survey was conducted among young antiretroviral therapy (ART)-naïve individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011–2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST.

Four of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C’-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate.

TDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C’-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.

Partial Text

The global scale up of antiretroviral therapy (ART) has resulted in decline in HIV related morbidity, mortality and HIV transmission. In most low and middle income countries (LMIC) standardized first line antiretroviral regimens are used, consisting of two nucleoside reverse transcriptase inhibitor (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI)] [1–3]. The emergence of HIV drug resistance (HIVDR), particularly towards drugs with low genetic barriers, eg. NNRTIs, has been shown to increase with time after introduction of ART programs [4]. One explanation for this is likely to be the lack of routine monitoring of plasma viral load, which has not been scaled up at the same rate as ART service expansion (ART roll-out) [2–9]. This leads to delayed identification of patients with treatment failure, with risk of accumulation of drug resistance mutations (DRM) in such individuals. Furthermore, individuals with unrecognized virological treatment failure are potential reservoirs for onwards transmission of viruses with DRM (commonly referred to as transmitted drug resistance; TDR) [2, 9–11]. If this occurs in populations with high incidence and at high risk of onward transmissions, the prevalence of drug resistant HIV strains may increase and be further amplified in the population [12]. Thus, the emergence of drug resistant viral strains constitutes a threat to the outcome of ART programs [13, 14]. Virological monitoring and resistance surveillance is therefore a priority [2].

This study represents the first threshold survey for DRM performed among young ART-naïve HIV-1 positive individuals in Gondar, Northern Ethiopia, using the WHO threshold methodology. We also used the sequence data obtained from drug resistance analysis together with sequence data obtained from previous studies for a detailed molecular epidemiological investigation of the HIV epidemic in Gondar. Detailed analysis stratified on the three subtype C clades identified transmission clusters in Gondar 2003–2013, which comprised 35% of all available sequences during this time. This finding indicated that HIV-1 has been introduced on multiple occasions, followed by local transmissions. Dated phylogenies revealed that about half of the local clusters originated before 2000. However, several of the clusters were long lasting and in some cases ongoing active transmission chains were detected. Importantly, we show that the G190A mutation has spread in Gondar by rapid transmission within local clusters. Even though DRM transmission within clusters has been described in other parts of the world, this is, to our knowledge, the first example of cluster-associated DRM transmission in sub Saharan Africa.

 

Source:

http://doi.org/10.1371/journal.pone.0205446

 

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