LONDON – Worldwide progress in treating HIV infection is threatened by a rising trend of resistance to antiretroviral drugs, according to the 2017 World Health Organization (WHO) HIV Drug Resistance report, due to be launched at the International AIDS Society conference in Paris on Sunday.

In response, WHO is issuing new guidelines on monitoring resistance and when countries should change drug regimens to block the increase in resistant infections, as part of a new global action plan, which will be presented at the conference.

While resistance is emerging globally, it is a particular threat in low income countries that depend on treatment with the cheapest non-nucleoside reverse inhibitor drugs and cannot afford newer integrase inhibitors or combination therapies.

In six of 11 such countries in Africa, Asia and Latin America that have conducted national surveys, 10 percent or more of people newly diagnosed with HIV were infected with a strain of the virus that was resistant to the two most widely used drugs in first-line therapy, efavirenz and nevirapine.

With many more countries due to complete surveys of resistance using a standardized WHO methodology, there is not yet a complete picture. However, a systematic review of published data conducted by WHO indicates that resistance is increasing in all regions of the world.

"Look[ing] at the trend, the level of resistance is increasing, it is a warning signal we need to take very seriously," said Gottfried Hirnschall, director of WHO's HIV department and global hepatitis program.

"When levels of HIV drug resistance [go over] 10 percent, we recommend that countries shift to an alternative first-line therapy for those who are starting treatment," Hirnschall told attendees of a teleconference held to discuss the report.

In 2016, 1 million people died of AIDS-related causes. In all, 1.8 million were newly infected with HIV, bringing the total number of infections to 37 million.

A mathematical model commissioned by WHO to assess the impact of growing resistance shows there could be an additional 135,000 deaths and 105,000 more new infections over the next five years, unless action is taken.

WHO's recommendation to switch from non-nucleoside reverse inhibitors to the integrase inhibitor dolutegravir would cost an additional $650 million over that time.

Meg Doherty, coordinator for HIV treatment and care at WHO, said that more than 100 countries and 350 partners contributed to the global action plan.

There is broad agreement that 10 percent resistance is the threshold at which first-line treatment should switch to dolutegravir.

"Countries need to do surveys to see when and how to modify first-line therapy. The good news is that we have alternatives ready," Doherty said. Some countries already are using integrase inhibitors to treat people with newly diagnosed HIV infections.

The 90:90:90 objective

Rising resistance to antiretroviral therapy could undermine the United Nations' 90:90:90 target of diagnosing, treating and suppressing the viral load in 90 percent of people who are infected with HIV by 2030.

There has been steady progress toward that objective, and at the end of 2016, 70 percent of those infected were diagnosed, of whom 77 percent received antiretroviral therapy, which was effective in 82 percent of cases.

"The good news is there is major progress, more and more people are getting treatment and for most people treatment works," Hirnschall said. "But at the same time we see drug resistance has evolved and there is a rising level of resistance against first-line therapy."

WHO's mathematical model predicts the 90:90:90 target will not be met in sub-Saharan Africa if resistance levels in those countries goes over the 10 percent threshold and no action is taken in response.

"Preventing, monitoring and responding to HIV drug resistance is critical to maintaining current achievements," WHO's report noted.

Resistance to antiretroviral drugs was first reported in 2001 and has been steadily increasing ever since. WHO started following resistance levels in 2004 and in 2014 provided updated guidance on how to monitor the problem, including the standardized survey methodology.

"Many more countries will have to do similar studies. We advocate every country carries out a survey so we get a representative sample," said Hirnschall.

A total of 19.5 million people were taking anti-HIV therapy at the end of 2016.

To reach the 90:90:90 objective, a further 17.2 million people would need access.

But that would mean 36.7 million people must be maintained on therapy for life.

"As efforts are made to scale up treatment there will be further increases in the level of resistance," WHO said.

In addition to the sheer number, the problem of ensuring adherence to life-long treatment, drug shortages and a lack of viral load testing facilities are further spurs to the development of resistance.

Silvia Bartagnolio, medical officer, HIV treatment and care at WHO, said overall the position is better than is the case for drug-resistant tuberculosis.

"We have a strong pipeline of new drugs that work against the virus in new ways. Dolutegravir is particularly effective, with few side effects, and it seems to have a protective effect against the development of resistance," she said.