Genetic Analysis of the Near Full-Length Genome of an HIV Type 1 A1/C Unique Recombinant Form from Northern South Africa Benson C. Iweriebor, 1 Pascal O. Bessong, 1 Lufuno G. Mavhandu, 1 Tracy M. Masebe, 1 Julius Nwobegahay, 1 Sylvester R. Moyo, 2 and Jeffrey M. Mphahlele 3 Abstract Human immunodeficiency virus type 1 (HIV-1) has a high propensity for recombination. The epidemic in South Africa is predominantly driven by HIV-1 subtype C with occasional description of non-subtype C and inter- subtype recombinant viruses. This report presents the genetic analysis of a unique recombinant variant from northern South Africa comprised exclusively of subsubtype A1 and subtype C parental viruses. Boot scanning analysis of the near full-length genome with the jumping profile Hidden Markov Model revealed a genomic arrangement with seven breakpoints of recombination alternating between subsubtype A1 and subtype C. Apparently, this is the first report of a unique HIV-1 A1/C recombinant form from northern South Africa and probably the fifth from South Africa. The epidemiologic implication of this variant is unknown. H uman immunodeficiency viruses (HIV-1 and HIV-2) are the etiologic agents of AIDS. HIV-1 is driving the epidemic worldwide, while HIV-2 is largely restricted to West Africa. Genetic variation and recombination are hallmarks of HIV-1. Phylogenetic analysis of HIV-1 isolates from various parts of the world has revealed three distinct groups: M, N, O, and a recently proposed group P. 1 Group M, which is re- sponsible for the global epidemic, is further subdivided into subtypes A–D, F–H, J, and K, subsubtypes A1, A2, A3, F1, and F2, in addition to circulating recombinant forms (CRF) and unique recombinant forms (URF) (www.hiv.lanl.gov). The distribution of HIV-1 subtypes in the world is heterogeneous with subtype B largely responsible for the epidemic in the Americas and Europe. Most subtypes are found in the Central African region, while subtype C is driving the epidemic in Southern Africa and India, with increasing detection in South America. 2–4 Globally, HIV-1 subtype C accounts for more than 50% of infections. 5 Although subtype C viruses overwhelmingly dominate the epidemic in South Africa, evidence is available on the circu- lation of non HIV-1 subtype C and recombinant viruses, albeit in low numbers. 6–9 The vast genetic diversity of HIV isolates and the evolution and spread of novel recombinants pose challenges on the efficacy of diagnostic tools, treatment and treatment monitoring tools, and the evaluation of candidate vaccines. 10–12 The present study genetically characterizes the near full-length genome of a primary isolate from an indi- vidual in northern South Africa, and shows that the isolate has unique recombinant patterns consisting of genomic regions from HIV-1 subsubtype A1 and subtype C parental viruses. Virus 08BBCR06ZA was obtained from a 33-year-old married female who at the time of blood collection was re- siding in Bela Bela in the Waterberg District of South Africa. In November 2008 5 ml of venous blood was collected within the context of a genetic drug resistance study. The patient was not on antiretroviral treatment. Her CD4 count and plasma RNA viral load measurements were 38 cells/ml and 60,237 copies/ ml, respectively. Ethical approval for the study was obtained from the Health, Safety and Research Ethics Committee of the University of Venda, and permission from the Limpopo Provincial Department of Health. Viral RNA was isolated from plasma using the QIAmp viral RNA mini kit (Qiagen) according to the manufacturer’s instructions. Initial genetic analysis of the complete protease and the partial reverse transcriptase (1296 nucleotides) indi- cated a subtype assignment of A1 and C, respectively. This observation prompted further investigation of the genomic make up of the isolate since from our previous studies on HIV genetic diversity from about 300 patients based on sub- genomic analysis about 99% were pure HIV-1 subtype C with 1 AIDS Virus Research Laboratory, Department of Microbiology, University of Venda, Thohoyandou, South Africa. 2 School of Health Sciences, National Polytechnic, Windhoek, Namibia. 3 HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Medunsa, South Africa. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 27, Number 8, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2010.0286 911