Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe
Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years.
Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).
Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0-7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%.
The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term.
Available from: Pleuni Pennings
- "The Plato II study (Nakagawa et al. 2012) showed that, in Europe, the prevalence of patients who had failed on all three major drug classes (NRTI, NNRTI and PI) increased steadily after 1996, but remained stable from 2005. 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). "
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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.
Available from: Santiago Pérez-Hoyos
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ABSTRACT: Background. Low CD4 counts are the main factor leading to clinical progression in HIV-1 infection. We aimed to investigate factors affecting CD4 counts after triple-class virological failure (VF).Methods. We included individuals with triple-class VF who started ART since 1998 from the COHERE database. CD4 counts from triple-class VF onwards were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23,922 CD4 values. In adjusted models (excluding current viral load and year), CD4 counts were higher with regimens which included boosted protease inhibitors (+22 cells/µL, 95% CI 3.9-41, p=0.017) or drugs from the new classes (+39; 15-62, p=0.001) when compared to NNRTI based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared to viral load levels <2.5 log(10) copies/mL, levels from 2.5-3.5, 3.5-4.5, 4.5-5.5 and >5.5 log(10) copies/mL were associated with lower CD4 counts of 51, 84, 137 and 186 cells/µL, respectively(p<0.001).Conclusions. The approximately linear relationship between log viral load and CD4 indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4 counts and few drug options.
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