Tenofovir is an antiretroviral drug that plays a critical role in most modern HIV treatment and prevention strategies. However, according to a large study funded by the Wellcome Trust, HIV resistance to tenofovir is becoming surprisingly and worryingly common.
The study was conducted by researchers from Stanford University in the United States and the London School of Hygiene and Tropical Medicine in the United Kingdom. The researchers studied 1,926 HIV patients around the world who had uncontrolled HIV in their bodies despite being on antiretroviral drugs. The researchers found tenofovir-resistant strains of HIV in 60 percent of patients in sub-Saharan Africa, compared with 20 percent of patients treated in Europe. About two-thirds of patients with tenofovir-resistant HIV strains were also resistant to the other two drugs in their treatment regimen. The findings were published online Jan. 28, 2016, in the journal Lancet Infectious Diseases.
The study suggests that up to 15 percent of HIV patients treated with tenofovir-containing drug combinations in sub-Saharan Africa will develop tenofovir resistance within the first year of treatment, and this number will rise over time. Tenofovir-resistant HIV strains can also be passed on to others and become more common, potentially undermining global HIV control strategies.
Tenofovir is a critical weapon in our arsenal against HIV, so it is very concerning to see such high levels of resistance to this drug,” explained paper author Dr. Ravi Gupta. It is a very potent drug with few side effects, and there is no good alternative available in public health measures. Tenofovir is used not only to treat HIV, but also to prevent HIV in high-risk populations, so we urgently need to put more effort into addressing this emerging resistance problem.”
Drug resistance usually develops when patients are unable to take the drug very regularly, so to make first-line therapy work, patients generally need to take the drug at least 85 to 90 percent of the time they are on it. When treatment is interrupted, the HIV virus is able to develop resistance to the drug. Previous studies have demonstrated that tenofovir-resistant HIV strains are less likely to proliferate and spread under laboratory conditions. However, it is not clear whether the virus is more unlikely to spread under real-world conditions.
In this study, patients whose immune systems were compromised when they started treatment with tenofovir had more than a 50 percent probability of developing resistance, as did those treated with a combination of tenofovir and certain other antiretroviral drugs. In many parts of sub-Saharan Africa, especially in rural areas, drug availability is limited, so patients receive treatment only when they develop advanced HIV disease. The problem is that at this stage, the patient’s immune system is much weaker, so the drugs do not fight the virus alone, but rather increase the likelihood of drug treatment failure and the development of drug resistance.
Once the HIV virus in the patient’s body becomes resistant to the first-line drugs, the next step is to receive expensive second-line drugs with more side effects. Many rural patients do not have access to these drugs, so it is important to try to maintain the effectiveness of first-line drug therapy.
Public health agencies and global funders have been very effective in getting antiretroviral drug regimens to the growing number of patients who need them,” said paper co-author Professor Robert Shafer of Stanford University School of Medicine. This study highlights the need to also take action to ensure that the medical regimens used to treat HIV remain effective for as long as possible.”