Timing of ART Initiation Impacts Cardiovascular Disease Risk in HIV Patients

A recent study addressed the relationship between initiation of antiretroviral therapy (ART) for HIV and its impact on cardiovascular disease (CVD) risk from already published data.

Two prior studies called Early Antiretrovirals and Isoniazid Preventive Therapy in Africa (TEMPRANO) and the Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) helped strongly support the benefit of ART for asymptomatic HIV-infected patients with high CD4 counts.

Both TEMPRANO and START saw over a 40% reduction in the risk of mortality or acquired AIDS when ART was initiated immediately, instead of waiting until CD4 thresholds were met. There was also a decreased risk of opportunistic infections and appreciable, but nonsignificant, reductions in all-cause mortality.

However, the rate of CVD events did not differ between immediate ART initiation and those who deferred therapy (adjusted hazard ratio, 0.84; 95% confidence interval [CI], .39—1.81; P = .65), which was an unexpected result of the START study.

In the Strategies for Management of Antiretroviral Therapy (SMART) study, published in Open Forum Infectious Diseases, researchers compared CD4 count guided treatment interruptions with continuous ART.

Around 5000 randomized HIV patients on stable ART with a CD4 count above 350 to continuing ART, compared with mandated treatment interruptions until CD4 counts dropped below 250 and ART was reinitiated.

The results of the SMART study found a 70% increase in CVD events in patients with treatment interruptions, while the START study found no increased risk of cardiovascular complications when initiation of ART was deferred.

When determining the timing of ART initiation and CVD risks, researchers came to 3 conclusions. Since data from the SMART study and other nonrandomized studies found an association between lower CD4 and increased risk of CVD, researchers believe that earlier initiation of ART can have a protective effect against CVD events.

Additionally, in combination with the SMART study results, the data supported continuous ART for patients who initiated therapy in order to prevent chronic inflammation associated with HIV, and lead to risk of CVD

Lastly, data from the START study suggests that patients with a CD4 threshold of 500 cells/uL when starting ART have marginal benefits as far as mitigating CVD risk when initiating ART early.

Further consideration should be taken on non-ART interventions to decrease risk of CVD in HIV patients initiating therapy with preserved immune function, the study concluded.