People with HIV who naturally control the virus without antiretroviral therapy were about twice as likely as HIV-negative people to develop non-AIDS-defining health problems, raising questions about whether they should receive treatment.

While most people with untreated HIV have a substantial viral load and a declining CD4 count and eventually experience disease progression, a small proportion—estimated to be less than 1%—maintain a very low viral load without antiretrovirals. Nonetheless, untreated HIV may result in persistent immune activation and inflammation that can lead to a wide range of health problems.

Carmelite Manto, of Université Paris Saclay, and colleagues compared outcomes among 227 spontaneous HIV controllers and 328 people on antiretroviral therapy from two French cohorts. People in the first group had been HIV positive for at least five years, had never taken antiretrovirals and had at least five consecutive viral load measurements below 400. Those in the latter group started anti-retrovirals within one month after a primary HIV diagnosis, achieved an undetectable viral load within 12 months and maintained viral suppression for at least five years.

During follow-up, 68 people in the HIV controller group and 62 people on antiretroviral treatment experienced non-AIDS-defining events. Rates of non-AIDS cancers and cardiovascular, pulmonary, liver and psychiatric events were similar in both groups. But HIV controllers had two times more non-AIDS infections, none of which were severe.

These results, the study authors suggest, “do not argue in favor of expanding the antiretroviral therapy indication for [HIV controllers] but rather a case-by-case approach considering clinical outcomes such as non-AIDS-defining events besides immune activation.”