Selection of human immunodeficiency virus type 1 variants with an insertion mutation in the p6(gag) and p6(pol) genes under highly active antiretroviral therapy.

We detected several types of human immunodeficiency virus type 1 (HIV-1) variants with an insertion mutation in the p6(gag)and p6(pol) genes in eight of twenty-two (36.4%) patients who possessed drug-resistant viruses under highly active antiretroviral therapy (HAART). It was characteristic that a conserved proline-rich motif "PTAPP" in the N-terminus of p6(gag) protein was completely or partially duplicated in all cases. Five among the eight cases were retrospectively investigated in terms of the occurrence of dynamic change in the gag gene between the inserted and wild-type HIV-1 in the course of HAART. The longitudinal analysis revealed the following: 1) The inserted-type viruses were selected over the wild-type during HAART in three cases in which the both types coexisted in the beginning of the therapy. 2) In two cases in which the inserted-type HIV-1 alone was detected before the beginning of HAART, the inserted-type HIV-1 alone was continuously detected during the therapy. The inserted-type HIV-1 was also detected in four of thirty-nine (10.3%) therapy-naive patients. However, the frequency of inserted-type HIV-1 detection in the HAART-receiving patients is significantly higher than that in the therapy-naive patients (P = 0.02). These results suggest that this type of insertion mutation is a polymorphism of the p6(gag) and p6(pol) genes, however, it consequently gave an advantage on proliferation and/or survival of the HIV-1 variant under the presence of antiretroviral drugs.