Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study

The Lancet Infectious Diseases (Impact Factor: 22.43). 02/2012; 12(2):119-27. DOI: 10.1016/S1473-3099(11)70248-1
Source: PubMed


Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09.
In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF.
28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22).
A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs.

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Available from: Carlo Torti, Dec 17, 2015
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    • "In general, efficacy of first-line HAART exceeds 80%, measured by the proportion of patients with a viral load below the detection limit [3]. But even after repeated treatment modifications including a variety of substance combinations, the rate of successful therapies has improved continuously over recent years [4]. Therefore, a viral load below the detection limit is currently one of the cornerstones of patient management. "
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    • "This is probably because the incidence of multi-class resistance went down, which, in turn, can be attributed to improvements in monitoring, simpler and less toxic regimens, which led to better adherence, and better pharmacodynamics, which made regimes more robust to sub-optimal adherence (Lundgren, 2012). As the risk of multi-class drug resistance went down, the chances of successful treatment for patients with multi-class resistant virus improved over the last decade (Castagliola et al., 2012). This is mainly due to the fact that several new drugs entered the market, such as raltegravir (INSTI) and darunavir (PI). "
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    ABSTRACT: Access to combination antiretroviral treatment (ART) has improved greatly over recent years. At the end of 2011, more than eight million HIV-infected people were receiving ART in low-income and middle-income countries. ART generally works well in keeping the virus suppressed and the patient healthy. However, treatment only works as long as the virus is not resistant against the drugs used. In the last decades, HIV treatments have become better and better at slowing down the evolution of drug resistance, so that some patients are treated for many years without having any resistance problems. However, for some patients, especially in low-income countries, drug resistance is still a serious threat to their health. This essay will review what is known about transmitted and acquired drug resistance, multi-class drug resistance, resistance to newer drugs, resistance due to treatment for the prevention of mother-to-child transmission, the role of minority variants (low-frequency drug-resistance mutations), and resistance due to pre-exposure prophylaxis.
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