To gain information about the genetic variation of the protease and reverse transcriptase gene-coding regions in HIV-1 strains belonging to CRF04_cpx, genotyping and drug susceptibility testing were performed on serum samples derived from seven patients carrying sequences belonging to this circulating recombinant form. Substitutions classically associated with resistance to antiretroviral drugs were observed in six of seven samples, including G48V, V82A, L90M, M46I in the protease protein, and K70R, D69D/N, M184V, T215F, K103N in the reverse transcriptase protein. Genotypic resistance patterns of CRF04_cpx samples were found to be similar to those identified in subtype B viruses, suggesting that the drug-selective pressure has similar effects on both subtype B and CRF04_cpx.