HIV-1 subtype C reverse transcriptase and protease genotypes in Zimbabwean patients failing antiretroviral therapy

Abstract

HIV-1 drug resistance mutations have been identified and characterized mostly in subtype B HIV-1 infection. The extent to which antiretroviral drugs select for drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1 reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients failing antiretroviral drug therapy. We compared these sequences with 56 published RT and protease subtype C sequences from untreated patients, 990 RT and 1140 protease subtype B sequences from treated patients, and 340 RT and 907 protease subtype B sequences from untreated patients and identified four mutation categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug resistance mutations. Mutations at 15 RT and 11 protease positions were more common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected individuals receiving antiretroviral therapy develop many of the known subtype B drug resistance mutations. Comparison of subtype C RT and protease sequences with a large database of subtype B sequences identified subtype C-specific polymorphisms and candidate drug resistance mutations.

FIG. 1

Prevalence of HIV-1 RT mutations in 21 subtype C isolates from patients receiving antiretroviral therapy: Comparison with subtype C isolates from untreated patients and subtype B isolates from treated and untreated patients. Shown are only those positions at which two or more mutations were observed in study patients; boxes mark positions associated with drug resistance in subtype B; RT isolates from study patients were compared with 990 isolates from treated patients infected with subtype B, 340 isolates from untreated patients infected with subtype B, and 56 isolates from untreated patients infected with subtype C.

FIG. 2

Prevalence of HIV-1 protease mutations in 18 subtype C isolates from patients receiving antiretroviral therapy: Comparison with subtype C isolates from untreated patients and subtype B isolates from treated and untreated patients. Shown are only those positions at which two or more mutations were observed in study patients; boxes mark positions associated with drug resistance in subtype B; protease isolates from study patients were compared with 1140 isolates from treated patients infected with subtype B, 907 isolates from untreated patients infected with subtype B, and 56 isolates from untreated patients infected with subtype C.