Revised European HIV Treatment Guidelines Emphasize Management of Age-related Non-AIDS Conditions and Coinfections

SUMMARY: The European AIDS Clinical Society (EACS) released updated HIV treatment guidelines last week at the group's annual conference in Cologne. According to the new recommendations, HIV positive adults should begin antiretroviral therapy (ART) when their CD4 cell count falls to 350 cells/mm3, but may benefit from starting sooner. The new guidelines place more emphasis on screening and management of chronic age-related conditions such as cardiovascular disease and neurocognitive impairment, as well as treatment of co-existing diseases including hepatitis B and C and tuberculosis.

By Liz Highleyman

The latest European guidelines, like the current U.S. Department of Health and Human Services (DHHS) guidelines, reflect the shift toward earlier therapy, as studies increasingly point to detrimental effects of even low-level HIV replication, well before the CD4 count falls into the "danger zone" for opportunistic infections (below 200 cells/mm3).

The EACS guidelines -- last updated in 2007 -- now recommend that people with HIV should initiate treatment before their CD4 count falls below 350 cells/mm3, and indicate that it may be beneficial to start as early as 500 cells/mm3. This is similar to the DHHS guidelines, which recommend treatment as soon as the CD4 count falls below 350 cells/mm3 and state that "[t]he optimal time to initiate therapy in asymptomatic patients with CD4 count > 350 cells/mm3 is not well defined."

Furthermore, the new European guidelines recommend that certain groups of HIV positive people should start ART within the 350-500 cells/mm3 range, including those with hepatitis C virus (HCV) coinfection, hepatitis B virus (HBV) coinfection requiring treatment, and HIV-associated nephropathy (kidney disease).

Research has shown that HCV-related liver disease progresses less rapidly in people with well-preserved immune function. Treating hepatitis B with dually active agents (e.g., tenofovir [Viread]) as part of a complete ART regimen can help prevent drug resistance. The DHHS guidelines recommend ART regardless of CD4 count for people with HIV/HBV coinfection and kidney disease, but not HIV/HCV coinfection.

The European guidelines also suggest that treatment should be considered below 500 cells/mm3 for people at greater risk for disease progression or poor response to therapy -- including individuals over 50 years old, those with high viral load (>100,000 copies/mL), and those with rapid CD4 cell decline (>50-100 cells/mm3 per year) -- as well as people with cancer or elevated cardiovascular disease risk.

The EACS guidelines advise that pregnant women should consider ART within the 350-500 cells/mm3 range. The U.S. guidelines, in contrast, recommend that all pregnant women should be treated regardless of CD4 count, based on the finding that combination therapy -- rather than use of specific single drugs such as zidovudine (AZT, Retrovir) to prevent mother-to-child HIV transmission -- provides more benefit for the pregnant woman's health and lessens the risk of drug resistance.

While people with a CD4 count above 500 cells/mm3 generally do not need to start treatment, the guidelines state that ART "can be offered on an individual basis, especially if patient is seeking and ready for ARV therapy." In presenting the guidelines, panel members noted that this could be applicable to HIV positive individuals with HIV negative partners, reflecting a growing emphasis on "treatment as prevention." The chances of HIV transmission are dramatically reduced if the positive partner takes ART and maintains an undetectable viral load.

With regard to which drugs to use for first-line ART, the new guidelines add ritonavir-boosted darunavir (Prezista) and boosted atazanavir (Reyataz) as recommended agents, with boosted fosamprenavir (Lexiva) and the integrase inhibitor raltegravir (Isentress) as alternatives. The guidelines also include recommendations for when to switch regimens -- for example, to reduce side effects or increase convenience -- in people with undetectable viral load.

The updated guidelines provide in-depth recommendations for screening, prevention, and treatment of several non-AIDS conditions that commonly affect people living with HIV, especially as they reach older ages. These include: