ABSTRACT
We investigated the occurrence of HIV-1 antiretroviral resistance in individuals failing to respond to highly active antiretroviral therapy (HAART) attended by RENAGENO from 2001-2004. One hundred and seventeen patients were selected for this study; their plasma viral RNA was extracted and the PR and RT genes sequenced to examine subtype, genetic polymorphisms and mutations associated with resistance to antiretroviral drugs. HIV-1 sequence analysis showed that 86/100 (86 percent) were infected with subtype B, 7/100 (7 percent) with subtype F and 7/100 (7 percent) with RT/PR hybrid forms (2 D/B, 2 F/B, 2 B/F and 1 D/F). In 14 (12 percent) of the samples, the subtype was not determined. The prevalence of resistance mutations was high (93.1 percent), mainly in the RT gene. The most prevalent resistance mutations were: M184V (60.7 percent), T215Y (49.6 percent) and M41L (46.7 percent) in the RT gene and L90M (19.6 percent), M46I (16.2 percent) and D30N (12.8 percent) in the PR gene. The frequency of resistance mutations tended to increase from the first to the second therapeutic scheme failure (p=0.079); but it stabilized after subsequent failures (p=0.875). Our finding of a high frequency of drug resistant HIV-1 samples supports the need for continuous genotypic monitoring of patients failing HAART.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1 , Brazil , Genotype , HIV Infections/drug therapy , HIV-1 , Mutation/genetics , Polymorphism, Genetic , RNA, Viral/genetics , Treatment Failure , Viral LoadABSTRACT
We investigated the occurrence of HIV-1 antiretroviral resistance in individuals failing to respond to highly active antiretroviral therapy (HAART) attended by RENAGENO from 2001-2004. One hundred and seventeen patients were selected for this study; their plasma viral RNA was extracted and the PR and RT genes sequenced to examine subtype, genetic polymorphisms and mutations associated with resistance to antiretroviral drugs. HIV-1 sequence analysis showed that 86/100 (86%) were infected with subtype B, 7/100 (7%) with subtype F and 7/100 (7%) with RT/PR hybrid forms (2 D/B, 2 F/B, 2 B/F and 1 D/F). In 14 (12%) of the samples, the subtype was not determined. The prevalence of resistance mutations was high (93.1%), mainly in the RT gene. The most prevalent resistance mutations were: M184V (60.7%), T215Y (49.6%) and M41L (46.7%) in the RT gene and L90M (19.6%), M46I (16.2%) and D30N (12.8%) in the PR gene. The frequency of resistance mutations tended to increase from the first to the second therapeutic scheme failure (p=0.079); but it stabilized after subsequent failures (p=0.875). Our finding of a high frequency of drug resistant HIV-1 samples supports the need for continuous genotypic monitoring of patients failing HAART.
Subject(s)
Antiretroviral Therapy, Highly Active , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Adult , Brazil , Female , Genotype , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/enzymology , Humans , Male , Middle Aged , Mutation/genetics , Polymorphism, Genetic , RNA, Viral/genetics , Treatment Failure , Viral LoadABSTRACT
The presence of genetic mutations in HIV-1-positive untreated individuals and its contribution to treatment failure, either in an individual or on a population basis, remains an important concern. The goal was to analyze and compare HIV-1 reverse transcriptase (RT) and protease (PR) genes of untreated individuals with chronic and recent infections. Fifty-one chronic infected individuals for whom initiation of antiretroviral treatment had been recommended and 20 individuals with recent documented HIV-1 seroconversion had their plasma viral RNA extracted and the PR and RT genes sequenced in order to determine subtype, presence of genetic polymorphisms and mutations associated with resistance to antiretroviral drugs. All 20 recent seroconvertors were infected with subtype B viruses. Of the 51 chronically infected patients, 40 (78.4%), 7 (13.7%), and 2 (3.9%) were infected with subtypes B, F, and C, respectively. Two (3.9%) hybrid forms were also observed in two individuals with chronic infection: D/B and D/F. Despite seroconversion stage, type and quantity of mutations were similar to both groups (P = 0.961). This group also presented the only (1.4%) drug-resistance mutation (M184V) among all samples investigated. In summary, the present study shows a high occurrence of equivalent polymorphisms unrelated to drug resistance in samples collected from untreated HIV-1- infected individuals in different seroconversion status, and suggests low primary resistance mutations. Results also indicate that non-B subtypes circulating in Rio de Janeiro have specific Brazilian non-synonymous mutations.
