The development of Resistance to Antiretroviral Therapy for HIV Infected Individuals: a Systematic Review (original) (raw)
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The global status of resistance to antiretroviral drugs
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2005
Since 1989, the emergence of resistant human immunodeficiency virus mutants has been documented for any new antiretroviral agent introduced in the clinical setting; it is a major cause of failure of antiretroviral therapy that may ultimately compromise the antiretroviral's efficacy in the general population. In most cases, resistance is due to poor adherence by the patient and/or to low potency of the therapeutic regimen. Resistance is called "primary" if detected in treatment-naive persons and is called "acquired" when it develops in treatment-experienced persons. This latter population represents potential transmitters of resistant viruses to newly infected persons. Data about the actual prevalence of resistance are derived from studies that differ in design, sample size, geographic area, and definitions. For this reason, a limited number of surveillance programs have been established in the past, both in countries where highly active antiretroviral therapy...
Indian Journal of Sexually Transmitted Diseases and AIDS
Background: About 10% of the patients had surveillance drug-related mutations for nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in an Indian study. It was also reported that resistance was maximum for nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs. Methods: The present study was a cross-sectional assessment of 21 human immunodeficiency virus (HIV)-infected individuals attending a HIV care center in a tertiary care center in Mumbai, Maharashtra, India. All HIV-infected individuals included in the present analysis were tested for CD4 count, viral load, and resistance to antiretrovirals (ARVs). Results: A total of 13 male and 8 female were included in the present analysis. Of these, 18 were treatment naive and three were treatment experienced patients. In treatment-naive patients, the proportion of high-level resistance (HLR) was 2% for NRTIs, 5% for PIs, and 11% for NNRTIs. In treatment-naive patients, high susceptibility was observed for darunavir (89%) followed by lopinavir (72%) and fosamprenavir (67%) among PIs. Similarly, susceptibility was high for NRTIs lamivudine (94%), emtricitabine (94%), and tenofovir (89%). However, we found HLR for nevirapine (39%) even in treatment-naive patients. Conclusions: The proportion of HLR was relatively low for PIs and NRTIs, compared with NNRTIs in treatment-naive patients. We also reported a high correlation in resistance patterns among drugs belonging to the same group. Thus, it may be useful to conduct ARV resistance even in newly infected HIV patients and those receiving medications for the first time.
The Journal of Infectious Diseases, 2004
Background. The prevalence and characteristics of persons with newly diagnosed human immunodeficiency virus (HIV) infections with or without evidence of mutations associated with drug resistance have not been well described. Methods. Drug-naive persons in whom HIV had been diagnosed during the previous 12 months and who did not have acquired immune deficiency syndrome were sequentially enrolled from 39 clinics and testing sites in 10 US cities during 1997-2001. Genotyping was conducted from HIV-amplification products, by automated sequencing. For specimens identified as having mutations previously associated with reduced antiretroviral-drug susceptibility, phenotypic testing was performed. Results. Of 1311 eligible participants, 1082 (83%) were enrolled and successfully tested; 8.3% had reverse transcriptase or major protease mutations associated with reduced antiretroviral-drug susceptibility. The prevalence of these mutations was 11.6% among men who had sex with men but was only 6.1% and 4.7% among women and heterosexual men, respectively. The prevalence was 5.4% and 7.9% among African American and Hispanic participants, respectively, and was 13.0% among whites. Among persons whose sexual partners reportedly took antiretroviral medications, the prevalence was 15.2%. Conclusions. Depending on the characteristics of the patients tested, HIV-genotype testing prior to the initiation of therapy would identify a substantial number of infected persons with mutations associated with reduced antiretroviral-drug susceptibility. Antiretroviral-drug resistance is an important cause of treatment failure in persons infected with HIV-1 and has been associated with increased mortality [1-4]. Although the transmission of drug-resistant strains of HIV has been well documented [5], the prevalence and characteristics
Journal of acquired immune deficiency syndromes (1999), 2015
Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management. Analysis of individual electronic health records from 4 HIV programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line antiretroviral therapy (ART) for ≥6 months. Adjusted logistic and Cox-regression models were used to identify risk factors for drug resistance and subsequent mortality. A total of 2257 patients (62% women) were included. At ART initiation, median CD4 cell count was 100 cells per microliter (interquartile range, 40-165). A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV RNA copies per milliliter. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to nevirapine, la...
Antiviral Therapy
To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug...
Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy
AIDS, 2004
Background and objective-The optimal time for changing failing antiretroviral therapy (ART) is not known. It involves balancing the risk of exhausting future treatment options against the risk of developing increased drug resistance. The frequency with which new drug-resistance mutations (DRM) developed and their potential consequences in patients continuing unchanged treatment despite persistent viremia were assessed.
AIDS (London, England), 2017
We estimated and compared the risk of clinically identified acquired drug resistance under i) immediate initiation (the currently recommended ART initiation strategy), ii) initiation with CD4 < 500, and iii) initiation with CD4 < 350 cells/mm. Cohort study based on routinely collected data from the HIV-CAUSAL Collaboration. For each individual, baseline was the earliest time when all eligibility criteria (ART-naïve, AIDS-free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 count, HIV-RNA, AIDS, ART regimen and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. In 50,981 eligible individuals, 10% had CD4 count>500 at baseline, and 63% initiated ART du...