Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.
نویسندگان
چکیده
BACKGROUND The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. METHODS We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. RESULTS Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. CONCLUSIONS Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.
منابع مشابه
Increased Risk of Q151M and K65R Mutations in Patients Failing Stavudine-Containing First-Line Antiretroviral Therapy in Cambodia
BACKGROUND Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitor...
متن کاملMulti-nucleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient from Sierra Leone failing stavudine, lamivudine and nevirapine.
We report a 33-year-old HIV type-1 (HIV-1)-infected male from Sierra Leone who harboured extensive drug resistance mutations to all nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs, including the multi-NRTI-resistance Q151M complex, K65R, M184I and Y181I, after using standard first-line generic fixed-dose stavudine, lamivudine and nevirapine (Triomune™) for 36 months. In the co...
متن کاملPatterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies.
BACKGROUND Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. METHODS A total of 2588 antiret...
متن کاملDrug- Resistance- Associated Mutations and HIV Sub-Type Determination in Drug-Naïve and HIV-Positive Patients under Treatment with Antiretroviral Drugs
Abstract Background and Objective: Resistance to antiretroviral agents is a significant concern in clinical management of HIV-infected individuals. Resistance is the result of mutations that develops in the viral protein targeted by antiretroviral agents. Material and Methods: In this cross-sectional study, the blood samples of 40 HIV-positive patients were collected. Twenty of them were d...
متن کاملEffect of stavudine-based antiretroviral therapy on the severity of polyneuropathy in HIV/AIDS patients: a preliminary report from Zaria, Northern Nigeria.
BACKGROUND Stavudine, a nucleoside reverse transcriptase inhibitor, used as first-line antiretroviral drug in many developing countries is said to exacerbate distal symmetrical polyneuropathy in HIV/AIDS patients. OBJECTIVE To evaluate the severity of distal symmetrical polyneuropathy in HIV/AIDS patients on stavudine-based antiretroviral therapy. METHODS Two hundred and twenty consecutive ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of infectious diseases
دوره 207 Suppl 2 شماره
صفحات -
تاریخ انتشار 2013