HIV-1 circulating recombinant form (CRF) 02_AG is responsible for greater than 65% of HIV-1 infections in Cameroon and is widespread across West and West-Central Africa. The parental subtypes A1 and G cocirculate in this part of Africa, and high rates of infection predispose to the generation of AG unique recombinant forms (URFs). Little is known as to whether A1 and G can recombine and thrive in vivo with breakpoints other than those characteristic of CRF02_AG. In this study, six unique recombinant viruses of subtypes A1 and G were identified in two individuals in Cameroon. A 1.5 kb fragment of the reverse transcriptase (RT) region of pol (HXB2 location 2,612-4,159) and the entire env gene (HXB2 location 6,202-9,096) were evaluated by phylogenetic and breakpoint analyses. Each URF was found to have breakpoints different than CRF02_AG, indicating that A and G gene segments are functionally compatible with more than one pattern of recombination. Furthermore, contemporaneous, cultured viruses from these individuals were analyzed, revealing different proportions of URFs compared to those found in plasma, possibly indicating compart mentalization and/or phenotypic variation among the URFs. CRF02_AG emerged from West-Central Africa to become a highly successful viral strain. As such, monitoring the spread of newly emerging AG recombinants is critical not only for understanding the epidemiology of HIV-1, but also in the design of future therapeutics and vaccines appropriate to this part of Africa, and globally.