Global HIV Treatment Guidelines May Be Revised Based on Study

A lead physician with the World Health Organization (WHO) says the Geneva-based group may change its guidelines for when HIV-infected individuals should start antiretroviral treatment (ART), a move that could potentially affect millions.

Current treatment guidelines in the US call for all asymptomatic HIV-infected individuals to begin treatment immediately, regardless of CD4+ T-cell count. Since 2013, WHO guidelines, which are adopted as the treatment standards in many developing countries, have recommended ART be started at any CD4 count for pregnant and breast-feeding women, all children less than five years old, all HIV-infected partners in so-called discordant relationships (where one partner is HIV-infected and the other isn’t), and people with HIV who are co-infected with TB or have severe Hepatitis B. For all others, the current WHO guidelines recommend ART initiation once CD4 counts falls below 500 cells/mm3.

The decision to revisit the guidelines for universal use is the result of the preliminary data from the START (Strategic Timing of Antiretroviral Treatment) trial that showed that HIV-infected volunteers receiving ART immediately were at a considerably lower risk of developing AIDS. The results were so clear that the trial was halted a year early so all participants could receivetreatment immediately rather than waiting. Together with data from previous studies showing that ART reduces the risk of HIV transmission to uninfected sexual partners, these findings point to the need to revisit treatment guidelines. 
  
“The WHO will convene its ART Guidelines Development Groups to systematically review the evidence on when to start treatment in low- and middle-income countries,” Doherty said. “This process will include a careful assessment of the START trial findings with a view to potentially revising global guidance on ART eligibility towards offering ART for all people living with HIV.” The group is meeting this month and will release its findings to the public when they have been cleared by the WHO’s Guidelines Review Committee, which conducts a final assessment, according to a WHO spokesperson.

The START study enrolled 4,685 HIV-infected men and women ages 18 and older, with a median age of 36. Participants had never taken ART and were enrolled with CD4+ T-cell counts in blood of about 500 cells/mm3. Half of the participants were randomly selected to receive ART immediately, while the other half were not treated until their CD4+ T-cell count declined to 350 cells/mm3. Most patients were followed for three years. Rates of serious AIDS-related events were lower in the immediate treatment group. Findings were consistent across geographic regions and levels of income.

Researchers and clinicians have been convinced for years that the earlier HIV therapy is started, the better people do. The START trial results, while underscoring the point more definitively, are not much of a surprise. In some places, immediate treatment is already showing peripheral benefits. The San Francisco Department of Public Health began recommending immediate treatment in 2010 and since then the number of new infections greatly decreased. Some researchers have therefore been critical of the WHO’s maintenance of guidelines less aggressive than standards for treatment in many developed countries, such as the US.

“For years now, treatment guidelines in the United States and other developed countries have advocated earlier treatment start thresholds than the World Health Organization has put forward for other countries,” said Timothy Lahey, an infectious diseases specialist and associate professor of medicine at Dartmouth College’s Geisel School of Medicine. “This is a mistake. Since the natural history of HIV and the efficacy of therapy are the same in the United States and in other countries, the treatment guidelines should be the same: Everyone should be started as soon as they are diagnosed and ready to start.”

The earlier treatment starts, the higher the costs of delivering these drugs, which in almost all cases must be taken for life. This isn’t trivial for already stretched budgets in many developing countries and without any increase in international funding. But according to Lahey this is no excuse. “What we should not do is systematically fool ourselves by setting inappropriately unambitious treatment goals and then feeling proud of the proportion of people who were treated according to them,” Lahey said. “We should set aside the idea that it’s a good idea to wait on HIV therapy, and do our best, amid a difficult reality, to get every single patient with HIV on therapy as soon as they feel ready.”

The WHO will publish updated ART guidelines by the end of the year, Doherty said, that include new clinical recommendations as well as guidance on how to implement new policies.

Implementation will obviously be key. “This will need to be a joint effort between country governments; United Nations agencies, including WHO, UNAIDS, UNICEF, among others; large international donors, such as The Bill & Melinda Gates Foundation, the US President’s Emergency Plan for AIDS Relief, and other donor countries; market-shaping efforts to continue to reduce ART pricing; and normative guidance from WHO to outline the most effective treatment approaches,” she said.

- Kitta MacPherson is a writer for VAX and IAVI Report in New York and an award-winning science journalist.