Prevalence and clinical implications of insertions in the HIV-1 p6Gag N-terminal region in drug-naive individuals initiating antiretroviral therapy.
We assessed the prevalence and clinical impact of insertions within the HIV-1 p6Gag 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 p6Gag 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 p6Gag 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 p6Gag insertions was observed on time to virological success (pVL < or = 500 copies/ml), virological failure (subsequent confirmed pVL > or = 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 p6Gag 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.
BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, British Columbia, Canada.
Zabrina L
ZL
Brumme
Keith J
KJ
Chan
Winnie W Y
WW
Dong
Brian
B
Wynhoven
Theresa
T
Mo
Robert S
RS
Hogg
Julio S G
JS
Montaner
Michael V
MV
O'Shaughnessy
P Richard
PR
Harrigan
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001955:British Columbia; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015683:Gene Products, gag / Q000235:genetics*; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D015995:Prevalence; D016016:Proportional Hazards Models; D016019:Survival Analysis; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1