Clade homogeneity and Pol gene polymorphisms in chronically HIV-1 infected antiretroviral treatment naive patients after the roll out of ART in Ethiopia

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Abstract

Background

Despite the increasing use of antiretroviral treatment (ART) recent data on frequency and pattern of drug resistance mutations in Ethiopia is not available. Furthermore with increasing mobility of people HIV-1 subtypes other than the predominant subtype C may likely be introduced from the neighbouring countries. This study was aimed to determine the molecular characterization and pre-antiretroviral treatment resistance mutations among HIV-1 chronically infected ART naïve patients after the roll out of ART in Ethiopia.

Methods

Viral RNA was determined in 160 baseline plasma samples. The entire PR and the first 335 codons (76%) of the RT regions of the pol gene of the HIV-1 genome (N = 160) were amplified and sequenced using an in-house assay. Genotypic drug resistance was defined as the presence of one or more resistance-related mutations as specified by the consensus mutation of Stanford University HIVDB and the International Antiviral Society (IAS) mutation lists.

Results

A predominance of HIV-1 subtype C (98.7%) was observed. The level of drug resistance is found to be 5.6% and 13.1% according to the Stanford University HIVDB drug resistance interpretation algorithms and the International Antiviral Society mutation lists, respectively. Mutations conferring simultaneous resistance to NRTIs and NNRTIs were not detected and no major PR mutation was found. However, a high rate of polymorphic changes both in PR and RT regions were observed. Moreover, twenty four (15%) monophyletic transmission clusters with bootstrap value of 99% were found.

Conclusions

Strong evidence for consistent HIV-1C clade homogeneity and low influx of other variant into the country was found. The level of drug resistance observed in chronically infected treatment naïve patients which exceeds the WHO estimates suggests the need for incorporation of HIV-1 drug resistance testing prior to ART initiation. The occurrence of monophyletic transmission clusters affecting (24/160) individuals indicates their potential risk related practice. Thus, an intensified public health intervention program and monitoring of HIV drug resistance testing appears indispensible.

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Most cited references 20

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HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance.

Diane Bennett, Daniel Kuritzkes, Soo-Yon Rhee … (2007)

Monitoring regional levels of transmitted HIV-1 resistance informs treatment guidelines and provides feedback on the success of HIV-1 prevention efforts. Surveillance programs for estimating the frequency of transmitted resistance are being developed in both industrialized and resource-poor countries. However, such programs will not produce comparable estimates unless a standardized list of drug-resistance mutations is used to define transmitted resistance. In this paper, we outline considerations for developing a list of drug-resistance mutations for epidemiologic estimates of transmitted resistance. First, the mutations should cause or contribute to drug resistance and should develop in persons receiving antiretroviral therapy. Second, the mutations should not occur as polymorphisms in the absence of therapy. Third, the mutation list should be applicable to all group M subtypes. Fourth, the mutation list should be simple, unambiguous, and parsimonious. Applying these considerations, we developed a list of 31 protease inhibitor-resistance mutations at 14 protease positions, 31 nucleoside reverse transcriptase inhibitor-resistance mutations at 15 reverse transcriptase positions, and 18 non-nucleoside reverse transcriptase inhibitor-resistance mutations at 10 reverse transcriptase positions. This list, which should be updated regularly using the same or similar criteria, can be used for genotypic surveillance of transmitted HIV-1 drug resistance.

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Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world.

Dineke Frentz, Charles A B Boucher, David A. M. C. Van de Vijver (2016)

A substantial number of studies have been performed across the world to determine transmitted drug resistance. Large variations between different parts of the world can be expected because of differences in availability over time of treatment. Time trend analyses are often not possible because of small numbers of included patients. In this review, we present the available data on the transmission of drug-resistant HIV, with a major emphasis on the time trends of drug resistance prevalences. We identified relevant literature by searching in PubMed through September 2009. Studies were grouped, according to the year of data collection, into the following time periods: 2003. We selected a total of 215 studies, which included 43,170 patients. The following prevalences of transmission of drug-resistant HIV were found, in rank order: North America (12.9%), Europe (10.9%), Latin America (6.3%), Africa (4.7%), and Asia (4.2%). Changes over time in particular drugs classes were found in all parts of the world. Nucleoside reverse transcriptase inhibitor resistance declined over time in North America (p = 0.03), Europe (p < 0.001), and Latin America (p < 0.001). The decline in nucleoside reverse transcriptase inhibitor resistance reflects the improvement of treatment regimens in resource-rich settings. In contrast the resistance prevalence increased in Asia (p = 0.047) and Africa (p < 0.001). This can be explained by the antiretrovirals becoming more available during recent years in these continents. Nonnucleoside reverse transcriptase inhibitor resistance rose over time in North America (p < 0.001), Europe (p < 0.001), Latin America (p < 0.001), and Asia (p = 0.01). This paper gives a complete overview of the epidemiology of resistance of antiretroviral drugs in drug-naive patients worldwide. The time trends that were observed seem to reflect changes in describing prescriptions over time. Changes include the more wide-spread use of antiretroviral drugs in developing countries and the development of therapies from low-active mono-therapies to highly active antiretroviral regimens in the industrialized countries.

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Update on HIV-1 diversity in Africa: a decade in review.

Raphael Lihana, Deogratius Ssemwanga, Alash'le Abimiku … (2015)

HIV-1 strains have diversified extensively through mutation and recombination since their initial transmission to human beings many decades ago in Central Africa in the first part of the 20th Century (between 1915 and 1941). The upward trend in global HIV-1 diversity has continued unabated, with newer groups, subtypes, and unique and circulating recombinants increasingly being reported, especially in Africa. In this review, we focus on the extensive diversity of HIV-1 over a decade (2000-2011), in 51 countries of the three African geographic regions (eastern and southern, western and central, and northern Africa) as per the WHO/UNAIDS 2010 classification. References for this review were identified through searches of PubMed, conference abstracts, Google Scholar, and Springer Online Archives Collection. We retrieved 273 citations, of which 200 reported HIV-1 diversity from Africa from January, 2000 to August, 2011. Articles resulting from these searches and relevant references cited in those articles were reviewed. Articles published in English and French were included. There has been a high diversity of HIV-1 in its epicenter, west-central Africa. A few subtypes, namely, A (A1, A2, A3, A4, A5), C, CRF02_AG, and D accounted for about 85% of new infections. Subtype A and D have been stable in East Africa; C in southern Africa; A, G, CRF02_AG, and CRF06_cpx in western Africa; and subtype B and CRF02_AG in northern Africa. Recently a new putative group, designated P, was reported to be found in two Cameroonians. The regional distributions of individual subtypes and recombinants are broadly stable, although unique/circulating recombinant forms may play an increasing role in the HIV pandemic. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity, and pathogenicity are crucial to the successful design of effective HIV vaccines. There is need for regular monitoring and review updates, such as the one presented here, to assist countries to plan and anticipate complex forms that may be introduced with time.

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Author and article information

Contributors

Andargachew Mulu

Thomas Lange

Uwe Gerd Liebert

Melanie Maier

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central

ISSN (Electronic): 1471-2334

Publication date Collection: 2014

Publication date (Electronic): 22 March 2014

Volume: 14

Page: 158

Affiliations

[1 ]Institute of Virology, Leipzig University Leipzig, Germany

[2 ]Department of Microbiology, College of Medicine and Health Sciences, University of Gondar Gondar, Ethiopia

Article

Publisher ID: 1471-2334-14-158

DOI: 10.1186/1471-2334-14-158

PMC ID: 3976149

PubMed ID: 24655349

SO-VID: b39392be-be8f-4df9-8e46-6147ba336968

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Clade homogeneity and Pol gene polymorphisms in chronically HIV-1 infected antiretroviral treatment naive patients after the roll out of ART in Ethiopia

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Abstract

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Most cited references 20

HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance.

Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world.

Update on HIV-1 diversity in Africa: a decade in review.

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