It’s one of the commonest and most effective anti-HIV drugs on the market, but resistance to tenofovir is alarmingly widespread, according to a new study. With the prevalence of resistance significantly higher than anticipated, the findings are particularly worrying given that scientists believed this to be a drug that HIV would be less prone to evolving defense mechanisms against.
Approved back in 2001, tenofovir is recommended by the World Health Organization (WHO) for first-line HIV therapy, alongside two other drugs – either lamivudine or emtricitabine and efavirenz. By administering multiple drugs at the same time, targeting HIV in different ways, the idea is that it’s more difficult for the virus to evolve ways to escape their action.
There’s no doubt that the regimens work well. They prevent the immune system from deteriorating and suppress replication to such an extent that the virus is undetectable, virtually abolishing the risk of transmission. But they’re not perfect and unfortunately fail in some patients, allowing the virus to bounce back and causing immune cells to become depleted.
Interestingly, resistance to tenofovir in these patients is uncommon in those from high-income settings, but much more prevalent in populations from low- or middle-income countries. Given the importance of this drug in managing the HIV pandemic, scientists led by a team at University College London decided to conduct a global investigation of tenofovir resistance in those experiencing treatment failure.
Using data from almost 2,000 patients living in 36 countries, the researchers found sub-Saharan Africa to be the worst affected, with greater than 50 percent of those studied showing resistance. This is in contrast to Europe, in which rates were a more modest 20 percent. In addition, the team identified risk factors for resistance, with the odds increasing by 50 percent if patients started off their regimen when their white blood cell counts were already low, or if efavirenz was traded for a different drug.
Tenofovir is also used as a preventive measure, called pre-exposure prophylaxis (shown). Marc Bruxelle/Shutterstock
Another important finding was that the amount of virus in patients experiencing treatment failure was similar regardless of whether they were resistant to tenofovir, while lab studies had suggested resistant viruses were compromised in their ability to replicate. Since higher amounts of virus in the body are linked with a greater risk of passing the virus on, this finding has significant implications for transmission.
“We certainly cannot dismiss the possibility that resistant strains can spread between people and should not be complacent,” lead author Dr. Ravi Gupta from UCL said in a statement. “We are now conducting further studies to get a more detailed picture of how tenofovir resistant viruses develop and spread.”
Writing in the Lancet Infectious Diseases, the team thinks the regional discrepancies observed might be down to patient monitoring. Those in high-income countries are checked far more frequently than those in poorer regions, which means that signs of failure will be picked up earlier in the former, giving doctors a chance to act before resistance has developed and change the drug regimen if necessary.
The problem doctors and health organizations now face is that second-line treatments are often expensive and come with serious side-effects, like zidovudine (AZT), which can actually reduce white blood cell counts. The take-home message is therefore that surveillance efforts need to be bumped up in order to prevent the situation from worsening and threatening to undo progress made so far.