Update on HIV-1 diversity in Africa: A decade in review

Center for Virus Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
AIDS reviews (Impact Factor: 3.79). 04/2012; 14(2):83-100.
Source: PubMed

ABSTRACT 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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Available from: Raphael Lihana, May 23, 2014
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    • "These CRFs have caused global epidemics. For example, CRF02_AG is common in West Central Africa, CRF07_BC and CRF08_BC are predominant in China [7], [8]. BF is mainly found in South America [9], [10]. "
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    ABSTRACT: Background Recombination is one of the major mechanisms underlying the generation of HIV-1 variability. Currently 61 circulating recombinant forms of HIV-1 have been identified. With the development of recombination detection techniques and accumulation of HIV-1 reference stains, more accurate mosaic structures of circulating recombinant forms (CRFs), like CRF04 and CRF06, have undergone repeated analysis and upgrades. Such revisions may also be necessary for other CRFs. Unlike previous studies, whose results are based primarily on a single recombination detection program, the current study was based on multiple recombination analysis, which may have produced more impartial results. Methods Representative references of 3 categories of intersubtype recombinants were selected, including BC recombinants (CRF07 and CRF08), BG recombinants (CRF23 and CRF24), and BF recombinants (CRF38 and CRF44). They were reanalyzed in detail using both the jumping profile hidden Markov model and RDP3. Results The results indicate that revisions and upgrades are very necessary and the entire re-analysis suggested 2 types of revision: (i) length of inserted fragments; and (ii) number of inserted fragments. The reanalysis also indicated that determination of small regions of about 200 bases or fewer should be performed with more caution. Conclusion Results indicated that the involvement of multiple recombination detection programs is very necessary. Additionally, results suggested two major challenges, one involving the difficulty of accurately determining the locations of breakpoints and the second involving identification of small regions of about 200 bases or fewer with greater caution. Both indicate the complexity of HIV-1 recombination. The resolution would depend critically on development of a recombination analysis algorithm, accumulation of HIV-1 stains, and a higher sequencing quality. With the changes in recombination pattern, phylogenetic relationships of some CRFs may also change. All these results may be critical to understand the role of recombination in a complex and dynamic HIV evolution.
    PLoS ONE 09/2014; 9(9):e107349. DOI:10.1371/journal.pone.0107349 · 3.23 Impact Factor
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    • "Previous studies have shown that, HIV-1C is predominantly circulating in 99% of the infected individuals in Ethiopia unlike other sub-Saharan-Eastern African countries [9,10]. However, with increasing mobility and migration of people, HIV-1 variants may be introduced and intermixed from the neighbouring countries where subtypes A, D, G as well as recombinant forms in Kenya and subtype D in Sudan are co-circulating [9,10]. "
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    ABSTRACT: 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 naive patients after the roll out of ART in Ethiopia. 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. A predominance of HIV-1 subtype C (98.7%) was observed. The level of drug resistance is found to be 5.0% and 12.5% 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. 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 naive 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.
    BMC Infectious Diseases 03/2014; 14(1):158. DOI:10.1186/1471-2334-14-158 · 2.61 Impact Factor
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    • "Based on phylogenetic analysis, HIV-1 strains have been divided into four major phylogenetic groups: M, N, O and P. Group M, the predominant circulating group responsible for the global HIV-1 pandemic [3], is divided into nine subtypes (designated A-D, F-H, and J-K) [2]. Some of the viral strains, such as subtypes A and F, have been further sub-divided into sub-subtypes A1-A5, and F1–F2, respectively [4]. In addition, different subtypes may recombine to form circulating recombinant forms (CRFs), which continue to be transmitted from one individual to another, or unique recombinant forms (URFs) if there is no evidence of transmission from the patient in which they arose to another. "
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    ABSTRACT: Increased understanding of the genetic diversity of HIV-1 is challenging but important in the development of an effective vaccine. We aimed to describe the distribution of HIV-1 subtypes in northern Tanzania among women enrolled in studies preparing for HIV-1 prevention trials (hospitality facility-worker cohorts), and among men and women in an open cohort demographic surveillance system (Kisesa cohort). The polymerase encompassing partial reverse transcriptase was sequenced and phylogenetic analysis performed and subtype determined. Questionnaires documented demographic data. We examined factors associated with subtype using multinomial logistic regression, adjusted for study, age, and sex. Among 140 individuals (125 women and 15 men), subtype A1 predominated (54, 39%), followed by C (46, 33%), D (25, 18%) and unique recombinant forms (URFs) (15, 11%). There was weak evidence to suggest different subtype frequencies by study (for example, 18% URFs in the Kisesa cohort versus 5-9% in the hospitality facility-worker cohorts; adjusted relative-risk ratio (aRR) = 2.35 [95% CI 0.59,9.32]; global p = 0.09). Compared to men, women were less likely to have subtype D versus A (aRR = 0.12 [95% CI 0.02,0.76]; global p = 0.05). There was a trend to suggest lower relative risk of subtype D compared to A with older age (aRR = 0.44 [95% CI 0.23,0.85] per 10 years; global p = 0.05). We observed multiple subtypes, confirming the complex genetic diversity of HIV-1 strains circulating in northern Tanzania, and found some differences between cohorts and by age and sex. This has important implications for vaccine design and development, providing opportunity to determine vaccine efficacy in diverse HIV-1 strains.
    PLoS ONE 12/2013; 8(12):e81848. DOI:10.1371/journal.pone.0081848 · 3.23 Impact Factor
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