BOSTON, MASS. – A day before the opening of the 2014 Conference on Retroviruses and Opportunistic Infections, the World Health Organization launched the March 2014 Supplement to the 2013 Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection here by reporting on some of the responses to the guidelines to date and offering featured presentations on sections of the new supplement.
With more than 10 million people now on HIV treatment in low-income countries, much of the supplement is an effort to offer guidance “as to the how,” said WHO HIV Director Gottfried Hirnschall. The supplement also highlights trends to help countries forecast their procurement needs. Expanding eligibility for antiretroviral therapy to adults with an immune cell, or CD4, count under 500 has been slow, Hirnschall said, while most countries have adopted immediate HIV treatment for HIV/TB co-infected patients. Many countries have moved to expand antiretroviral treatment eligibility to those also living with hepatitis B. At the same time, according to a presentation that followed, the treatment gap between adults and children is growing with only 34 percent of eligible children receiving antiretroviral treatment compared to 68 percent of adults.
The move away from stavudine, or D4T, a toxic antiretroviral with lasting side effects, also has been slow, the supplement shows, with the drug continuing to dominate as the first line of treatment in high HIV prevalence countries that include Zimbabwe and Malawi. Challenges to the transition include high numbers of patients and limited drug production capacity. Countries can prioritize patients experiencing side effects and patients with hepatitis B, who will benefit additionally from the alternative drug, but ultimately, the drug should be avoided, or reserved for “exceptional situations,” the supplement says. Despite progress on many fronts, in low-income countries, which are virtually the only places on the globe where D4T is still used, the number of people initiating treatment on D4T actually has increased since 2010, with about million people beginning to take the drug in 2012. Between 5 and 6 million patients are still on neviripine containing regimens—another drug that WHO flags as problematic, particularly for women with higher CD4 counts who are at risk for life-threatening side effects. WHO has seen a trend toward embracing fixed dose combinations for ART, but here there are fiscal challenges, since the single drug pills remain cheaper than the combinations. Research demonstrated a 12 percent improvement in adherence with fixed drug combinations compared to multiple pills. An audience member pointed out that the price differential will become an even greater issue with newer drugs, since those fixed dose combinations will remain on patent until at least 2020. Hirnschall told his audience to stay tuned for future guidance when dolutegravir in combination with lower doses of efavirenz and long-acting ripilvirine become available.
The supplement adds new information about strategies for diagnosing HIV infection among infants to expedite antiretroviral treatment initiation for this vulnerable group. Only 35 percent of infants received HIV virologic testing by 2 months of age, while deaths for untreated infected infants peak at the ages of 3 to 4 months. The supplement also includes discussion about optimizing antiretroviral drugs for children, with a list of priorities developed by an expert panel. WHO is revising its guidelines on HIV testing for infants and children and its guidelines for infant prophylaxis with a recommendation that the use of three drugs be considered.
Now that several million people in poor countries have been on antiretroviral treatment for more than 5 years, the best investment for monitoring treatment outcomes has become a more urgent matter, and the value of CD4 monitoring is raised. Viral load testing has been established as the gold standard for monitoring treatment but it remains expensive and unavailable to the general patient population in most countries. Since research shows that CD4 counts remain relatively stable in patients who are virally suppressed on antiretroviral treatment, the value of CD4 counts to monitor treatment effectiveness has diminished. A number of countries are considering stopping CD4 count monitoring among stable patients and others are moving to do these tests less frequently. A WHO consultation with people living with HIV indicated that patients might not be troubled with ceasing CD4 testing while on treatment provided that viral load monitoring is available.
The next supplement to the guidelines will be released in the fall, and will contain new recommendations for post-exposure prophylaxis antiretroviral drugs. Adherence to PEP regimens, at about 50 percent, has been found dismal, Nathan Ford from the WHO noted, and much worse among especially vulnerable groups that include sex workers and victims of sexual violence.