VIENNA — The increased efficacy of antiretroviral therapy for HIV has changed the nature of HIV infection.
“With [antiretroviral therapy] AIDS is preventable. Now we see an increased number of deaths due to diseases not usually thought to be part of HIV: cardiovascular, renal, hepatic, and malignancy,” Dr. Melanie A. Thompson said.
This new face of HIV led to some of the biggest changes in the 2010 adult HIV infection treatment recommendations from the International AIDS Society–USA. “The balance has tipped farther in favor of earlier initiation” of treatment, said Dr. Thompson, principal investigator of the AIDS Research Consortium of Atlanta and chairwoman of the recommendations panel. She introduced her group's revision of its 2008 recommendations the day before the 18th International AIDS Conference began (JAMA 2010;304:321-3).
The new treatment scheme calls for starting antiretroviral therapy (ART) in all symptomatic patients, all patients with at least one specific condition from a list of eight (several on the list are new), or asymptomatic patients with a CD4 cell count of 500/mcL or less (up from 350/mcL from the prior guidelines). The new approach also calls for considering treatment in any other patient infected by HIV, including asymptomatic patients with a CD4 cell count above 500/mcL. It's on that front that the recommendations break new ground.
Virus replication in these early-stage patients leads to “activation of the immune system and chronic inflammation,” with rises in inflammatory markers including C-reactive protein,
“At any CD4 cell count, the body will take a hit from uncontrolled HIV infection; that's what's driving earlier treatment. There is increasing evidence of the detrimental effects of uncontrolled viremia at CD4 cell counts above 500/mcL,” Dr. Thompson said. ART may also help prevent organ damage by normalizing inflammatory marker levels.
Another development that makes early treatment attractive is that physicians can now prescribe off a list of 23 different drugs from seven different classes. (See chart.) What's now available are “less toxic, more tolerable potent drug regimens that have shown durable responses, even in patients infected with multidrug-resistant HIV, and with lower risk for emergence of multidrug resistance.”
She estimated that 80%-90% of patients who have an early infection and are treatment naive can start ART and have their viral load immediately driven down to an undetectable level. Current regimens can also hold infections to an undetectable rate for 5 years or longer, according to outcomes achieved in trials, Dr. Thompson said in an interview. The only exceptions to starting treatment are asymptomatic patients with a high CD4 cell count who are either “elite controllers,” with no detectable HIV viremia, or those with a stable CD4 cell count and low-level viremia without treatment.
The recommendations panel included 16 members from eight countries. Their work began last January, and included publications from August 2008, the cutoff for the prior revision, and May 2010. The recommendations lay out optimal care today, and are aimed primarily at care in highly resourced settings. They cover five topics: when to start treatment, what to start, monitoring, when to change, and what to change.
Although initial therapy needs to be individualized, the basic approach is to combine two nucleoside analogue reverse transcriptase inhibitors plus a potent third agent from another drug class. The combination of tenofovir plus emtricitabine is the current “backbone” pairing, with abacavir plus lamivudine as the major alternative; recommended third agents are efavirenz, atazanavir, darunavir, or raltegravir.
The list of specific conditions that should definitely trigger treatment of asymptomatic patients, regardless of their CD4 cell count, are pregnancy, an HIV viremia of more than 100,000 RNA copies/mL, a rapid decline in CD4 cell count of more than 100/mcL in a year, active coinfection with hepatitis B or C virus, active or high risk for cardiovascular disease, HIV-associated nephropathy, symptomatic primary HIV infection, and a high risk for transmitting the virus.
The shift to earlier treatment spelled out in the new recommendations boosts the need for earlier diagnosis. “Most of our patients are diagnosed too late to benefit from early treatment,” said Dr. Thompson. “We need cheaper HIV testing, better testing, and broad-based testing. … The simple answer is universal testing.” But she also noted that many social and structural barriers to testing now exist.
The challenges of broad HIV screening appeared in results from a second study reported at the press briefing that compared two approaches for HIV testing in a Denver emergency department: physician-directed diagnostic testing, and routine screening of most presenting adults with an ability to opt out by checking a box on the consent form, an approach promoted by the Centers for Disease Control and Prevention in 2006 (MMWR Recomm. Rep. 2006;55[RR-14]:1-17).