Prevalence and clinical implications of insertions in the HIV-1 p6 Gag N-terminal region in drug-naive individuals initiating antiretroviral therapy

Abstract

We assessed the prevalence and clinical impact of insertions within the HIV-1 p6^Gag proline-rich (PTAP) region on initial antiretroviral therapy response in 461 HIV-infected, drug-naive individuals initiating therapy in British Columbia, Canada between June 1996 and August 1998. HIV p6^Gag insertions were detected by nested RT-PCR of extracted patient plasma followed by direct DNA sequencing. Insertions were observed in 70 of 423 successfully genotyped samples (16.5%). HIV p6^Gag insertions were significantly associated with a lower baseline CD4 cell count (P<<0.05) and the presence of basic amino acids at key positions in the HIV envelope V3 loop linked to a syncytium-inducing phenotype (P<<0.05). After adjusting for baseline factors, no effect of HIV p6^Gag insertions was observed on time to virological success (pVL ≤500 copies/ml), virological failure (subsequent confirmed pVL ≥500 copies/ml) or immunological failure (confirmed CD4 count below baseline), as evaluated by Kaplan-Meier methods and Cox proportional hazard regression (P>0.1). The data suggest that HIV p6^Gag insertions are not exclusively related to drug resistance and may not influence response to antiretroviral therapy, but may be linked to sequence variations in the HIV envelope.