Handling your HIV treatment can be tricky. There are so many questions: which meds to take, how to predict resistance, what to do if and when it appears. And scientific opinions on the optimal time to start HIV meds keep shifting. The picture just got murkier. Some leading researchers announced their latest theory: that people should start taking HIV meds earlier than what’s currently recommended. This approach, known as “hit hard, hit early,” lost its luster in the late 1990s, as the HIV combos that prolonged our lives also seemed to threaten our hearts, damage our other organs and wreck our health with a slew of side effects.
The “hit early” comeback is fueled by data suggesting that HIV itself may cause much of the damage we’ve been blaming on drug toxicities. So the fear that early treatment produces extra side effects seems suddenly old-fashioned. Instead, the new information implies that even when our CD4 counts are flying relatively high without meds, the virus puts us at increased risk for non-HIV-related problems. These include heart disease, stroke, kidney failure, liver damage and non-AIDS-defining cancers.
This is a radical departure from what we’ve heard over the past decade, when research suggested that long-term use of HIV meds worsens these conditions. For example, in one large international study involving more than 23,000 HIV-positive people, each additional year on HIV meds was associated with a 26 percent increase in heart-attack risk.
Now various studies show such health problems flourishing among positive people with CD4s as high as 700 who are not taking meds, says Fred Gordin, MD, of George Washington University. “When you match them against HIV-negative people or people on therapy,” Gordin says, “those off therapy have higher rates of [conditions].” Earlier this year another large study, Strategies for the management of Anti-Retroviral Therapy (SMART), found a greater risk of cardiovascular and kidney disease among those with high CD4 counts who stopped HIV meds than among those who continued to take them.
Some things haven’t changed. There’s no doubt that HIV drugs can increase artery-clogging fats in the bloodstream. But new results show that HIV meds may have heart-saving effects as well. Data from SMART link HIV meds with lower levels of d-dimer, possibly indicating less artery blockage. Other recent studies also show that being on HIV meds can improve blood vessel function.
How does HIV raise the risk of non-AIDS-related health problems in people with apparently robust immune systems? One theory blames the relentless cycle of CD4 cell infection and death caused by HIV. This cycle, Gordin suggests, creates an inflammatory response that may derail normal immune function, even if it doesn’t fully deplete the stock of CD4 cells. For HIV longtimers, the shifting theories may provide information on how to stay hardy through years of life with HIV.
Despite the conflicting studies, some docs are thinking practically rather than theoretically, helping positive people stay healthy while we await answers. Whether the non-AIDS problems result from HIV or the meds, “close monitoring and aggressive management of risk factors for things like cardiovascular disease and renal disease” may be the real key to maintaining overall health, says Paul Bellman, MD, a New York City-based HIV doctor. Mauro Schechter, MD, of the Federal University in Rio de Janeiro, adds a crucial point: Newer HIV meds provide simpler dosing, more power and fewer side effects, so starting earlier may not cause as much damage (or dosing burnout) as earlier regimens did.
To settle things, Gordin and an international team hope to initiate a 3,000-person trial—Strategic Timing of Antiretroviral Therapy (START)—comparing the results of starting meds at 500 versus 350 CD4s.
Not everyone cheers the effort. “It will cost a fortune,” says Martin Markowitz, MD, of the Aaron Diamond AIDS Research Center, adding “the long-run difference between immediate and delayed therapy is short.” In his experience, he says, the average time from HIV infection to a sub-350 CD4 count is about 2.7 years. Starting at 500 might mean a gap of a few months.
Bellman doesn’t knock START but puts other trials first. “I call for more work on immune pathogenesis and therapeutic and preventive vaccines,” he says, “to bear the greatest fruit in the global effort to prevent HIV and [improve treatment].” Markowitz agrees with that starting point for HIV research. “I would rather,” he says, “see the money spent trying to cure this infection.”