The U.S. Department of Health and Human Services (HHS) released updated HIV treatment guidelines on March 27 which, among other things, maintain that all people living with HIV in the U.S. are now eligible to receive antiretroviral therapy (ART), regardless of CD4 cell count. Previous guidance recommended ART for those HIV-infected with a CD4 cell count at or below 350, as well as between 350 and 500, but did not have a recommendation for those with a CD4 count above 500.
“This revised recommendation is based on a growing body of evidence demonstrating the harmful effects of ongoing HIV replication and on the results of the [HIV Prevention Trials Network (HPTN)] 052 study,” said Charles B. Hicks, MD, from Duke University Medical Center in an article for Journal Watch AIDS Clinical Care. HPTN 052 demonstrated that ART reduces the likelihood of HIV transmission to an uninfected sexual partner by 96 percent. In the guidelines, the Prevention of Secondary HIV Transmission section is updated to reflect the HPTN 052 study and the role of ART in reducing transmission.
“Although not new, the more enthusiastic endorsement of ART for all reflects a recognition of the range of benefits of treatment coupled with longer-term safety and tolerability data on contemporary ART regimens,” Hicks said.
Whether or not this U.S. guideline change could spur new global policy recommendations on ART eligibility from the World Health Organization has clinicians, advocates and health ministries wondering. The World Health Organization (WHO) was reportedly poised to issue guidance recommending ART for HIV-infected persons, regardless of CD4 count, in stable heterosexual partnerships at the International AIDS Society conference in Rome in July, but the agency pulled the recommendations at the last minute to consider other issues and, potentially, populations.
The treatment recommendation has various “strengths” (A = Strong, B = Moderate, C = Optional; I = data from randomized controlled trials, II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes, III = expert opinion), determined by the patient’s CD4 count before treatment initiation:
- CD4 count <350 cells/mm3 (AI)
- CD4 count 350 to 500 cells/mm3 (AII)
- CD4 count >500 cells/mm3 (BIII)
The guidelines also strongly recommend ART treatment regardless of CD4 cell count for HIV-infected persons who are pregnant (AI), have a history of an AIDS-defining illness (AI), have HIV-associated nephropathy (AII), or are co-infected with hepatitis B virus (AII). Providers are encouraged to offer ART to patients at risk of transmitting the virus to their sexual partners (AI [heterosexuals] or AIII [other transmission risk groups]).
The guidelines also included a new section on managing HIV in older patients as well as a new drug cost table that breaks down the 2012 monthly average wholesale price (AWP) for both generic and brand-named HIV drugs approved by the U.S. Food and Drug Administration, including fixed-dose combinations.
The guidance contains updated recommendations on when to initiate ART in HIV-infected patients diagnosed with tuberculosis (TB) who are not on ART to take into account recent trial data demonstrating a survival benefit when ART is initiated during TB treatment rather than after, and when ART is initiated within two weeks of TB treatment for those with a CD4 count less than 50. Those with CD4 counts greater than 50 determined to have clinical TB disease of “major severity” are recommended to start ART within two to four weeks of starting TB treatment; and those with CD4 greater than 50 who are healthy can be delayed beyond two to four weeks but should begin ART by weeks eight to 12 of TB treatment.
Guidance on co-administration of new hepatitis C drugs (protease inhibitors) with ART is also included. “A central concern with these important additions to the hepatitis C treatment arsenal is their drug-drug interaction profiles,” said reporter Tim Horn in an article on AIDSmeds.com. “As these drugs are broken down, or metabolized, via the same pathways as many HIV medications, the likelihood of interactions—resulting in reduced treatment efficacy and a higher risk of side effects—is significant.” The guidelines recommend using the Hep C drug telaprevir (Incivek) instead of boceprevir (Victrelis) when antiretroviral regimens that include ritonavir-boosted atazanavir or efavirenz are being used to treat HIV.