Extensive virological failure of the three main classes of HIV antiretroviral drugs occurs slowly in routine clinical practice. This finding is good news for the planning of treatment programmes in developing countries, where additional drugs outside these classes are unlikely to be available for some time. These are the conclusions of authors of an Article in this week's edition of The Lancet.
The three original main classes of HIV antiretroviral drugs are nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors. All these drugs work by suppressing HIV replication, so they are said to have failed when they lose their ability to suppress HIV viral load. Triple-class failure has generally been defined by virological failure of at least one drug in each of the three main classes, but more extensive failure is defined as extensive failure in all three classes. In developing countries, access to drugs will probably be restricted to the three original classes for years to come, so understanding the durability of the antiviral efficacy of these classes is crucial for long-term planning.
Professor Andrew Phillips, Royal Free and University College Medical School, London, UK, and colleagues used data from 7916 patients on from The UK Collaborative HIV Cohort Study (funded by the Medical Research Council) for their analysis. The average age of these patients was 36, and 25% of them were women. They had all started antiretroviral therapy with three or more drugs and were followed up for a maximum of 10 years (1405 patients were followed up for at least six years).
The researchers found that 167 patients developed extensive triple-class failure during follow up. The cumulative risk of triple-class failure was estimated at 9.2% by 10 years, with evidence that this rate has decreased by 14% per year in the time period covered. In these 167 patients, 101 (60%) subsequently had at least one viral load below 50 copies per ml, the lowest detectable level -- showing that the drugs retained some of the virological activity post-failure. At the time of extensive triple-class failure 90% of the 167 patients had virological failure of seven or more drugs. The risk of death by five years from the time of extensive triple-class failure was 10.6%.
The authors conclude: "Our study has shown that the rate at which patients starting antiretroviral therapy have extensive virological failure of the three main antiretroviral drug classes seems to be slow, especially in those with CD4-cell counts greater than 200 cells per µl at the start of therapy. Furthermore, there is evidence that the rate has decreased over time as drugs and experience with their use have improved...[this] is especially encouraging for developing countries where drug availability will probably be restricted to three original drug classes for some time."
In an accompanying Comment, Dr Edward Mills, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, and Dr Jean B. Nachega, Bloomberg School of Public Health, Department of International Health, Johns Hopkins University, Baltimore, MD, USA, say: "Phillips and colleagues' study underscores the need for access to alternative, less toxic, and more affordable first-line, second-line, and now third-line antiretroviral drugs in developing countries....because HIV/AIDS will be with us for the foreseeable future, we need a visionary response that treats poor patients as optimally as wealthier patients. In years to come, we will look back and wonder if we can really say we did the best we could.">/p>
Professor Andrew Phillips, Royal Free and University College Medical School, London, UK. T) +44 (0) 20 7830 2886 / +44 (0) 7738 181457 E) a.phillips@pcps.ucl.ac.uk
Dr Jean B. Nachega, Bloomberg School of Public Health, Department of International Health, Johns Hopkins University, Baltimore, MD, USA, T) +1 410-955-2378 E) jnachega@jhsph.edu
View the paper associated with this press release by clicking on the link below:
http://multimedia.thelancet.com/pdf/press/HIVdrugs.pdf
Journal
The Lancet