Since the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, many experts have come to favour prompt antiretroviral treatment early in the course of infection. This is done with the aim of delaying disease progression and preventing clinical illness. Some, including David Ho of the Aaron Diamond AIDS Research Centre, have argued that early treatment might lead to the eventual eradication of HIV from the body.1
The original US guidelines for the use of antiretroviral therapy, issued in 1998, called for starting treatment when the CD4 cell count fell below 500 cells/mm3. European experts, however, were more sceptical about the benefits of the 'hit early, hit hard' approach. Since HAART had only been recently introduced, there was no evidence from long-term studies to show whether starting therapy with a CD4 count of 500 cells/mm3, rather than later, provided any benefit in terms of delayed progression to AIDS or prolonged survival.
Not long after the widespread adoption of protease inhibitors, doctors and patients began to report unusual symptoms, including body fat changes (lipodystrophy). In the ensuing years, it became apparent that antiretroviral therapy was associated with a variety of metabolic complications, including elevated blood fat and blood sugar levels. Elevated blood fats were a particular concern, since they can increase the risk of cardiovascular disease.
There was also growing evidence that HIV could not be eradicated using existing drugs. Further, treatment failure due to the emergence of drug resistance, even in patients who started with potent combination regimens, underlined the importance of preserving future treatment options by not ‘using up’ available drugs before they were really needed. The issues of lifelong adherence to therapy and cost were also relevant ones.
However, in the mid-2000s, data from large clinical cohorts began to accumulate, suggesting that treatment earlier in the course of infection was associated with better outcomes and reducing both HIV-related and non-HIV-related clinical events.
The most common antiretroviral regimens used today by people starting treatment are less toxic than those used in the past. Hopefully, they will be less likely to cause long-term complications.
Many treatment guidelines now recommend starting antiretroviral therapy when the CD4 cell count is between 350 and 500 cells/mm3 as this timing is associated with better outcomes, including a greater likelihood of attaining near-normal CD4 cell counts. Additionally, other studies indicate that people are more likely to achieve undetectable HIV suppression if their pre-treatment viral load levels are relatively low.
Should the threshold for when to start treatment be raised higher? That is a question that additional clinical studies will need to address.
There are many factors to consider regarding the timing of antiretroviral therapy initiation and the most effective drugs to be included in a treatment regimen. Managing resistance and using drugs wisely is critical to staying healthy. The stakes are high. Clinicians need to be knowledgeable, experienced, and highly motivated to provide HIV care on a level that provides the best outcome to each patient, regardless of situation or setting.