Ability to control HIV without drugs rare and transient, but linked to better outcomes, study shows

Around 7% of people infected with HIV achieve undetectable levels of the virus in their blood without antiretroviral therapy, according to an analysis of data from the CASCADE study presented in the 18^th November edition of AIDS.

Spontaneous control of HIV was linked to a reduced risk of developing AIDS or dying. However, it was followed by loss of control of viral load and falls in CD4 cell count after around a year of undetectability, on average.

The study also found that women were more likely than men to control viral loads spontaneously, as were patients who did not have a seroconversion illness after becoming infected.

CASCADE is an international collaboration of researchers from Europe, Canada and Australia, which gathers information on patients whose date of HIV seroconversion can be estimated accurately. The collaborators wished to work out which factors are linked to the ability to control HIV spontaneously and the effects of spontaneous control of HIV on patients’ outcomes.

This analysis involved almost 2180 adult patients, of which 145 (7%) had at least two consecutive viral load measurements below 500 copies/ml without antiretroviral therapy.

In a ‘multivariate’ analysis, the researchers found that women were 2.15 times more likely to control their viral load than men (95% confidence interval [CI]: 1.49 – 3.12), whereas patients who did not have seroconversion illness were 1.72 times more likely to control viral load (95% CI: 1.06 – 2.78).

There was also a trend for patients with higher CD4 cell counts to achieve undetectable viral loads without treatment. At the start of the study, patients achieving undetectability had higher median CD4 cell counts (743 vs. 585 cells/mm³; p

In contrast, there was no link between age or ethnicity and the likelihood of a patient achieving undetectable viral load.

“Women were more likely to achieve undetectable viraemia than men, which agrees with previous findings showing that women exhibit lower viral load levels soon after seroconversion,” conclude the investigators. Patients without a symptomatic primary infection, with high baseline CD4 cell count or low baseline viral load were also more likely to control their viraemia without antiretroviral therapy during their infection.

“These results from a large multicohort collaboration strengthen the evidence for the existence of a small number of patients with prolonged spontaneous control of viral replication, the HIV controllers,” they write.

The ability to control viral load was linked to a reduced risk of developing AIDS in the era before the introduction of highly active antiretroviral therapy (HAART) in 1996 (0.66 vs. 3.43 per 100 person-years; p = 0.002). Since 1996, the number of new AIDS cases has fallen in patients who did not achieve undetectable viral loads but it has remained stable in those who spontaneously controlled their HIV levels. However, there was still a trend for the spontaneous controllers to have fewer AIDS cases.

Death rates in the two groups of patients followed a similar pattern.

The investigators found that the 145 patients achieved undetectable viral loads a median of 23.3 months after seroconversion. In at least 14 (10%) of these, undetectability occurred after at least one viral load test that showed detectable levels of HIV in the blood.

The median duration of undetectable viral load was 11.2 months, although one patient maintained an undetectable viral load for 88.0 months before viral load became detectable and 45 (31%) of the patients still had undetectable viral loads at the end of the follow-up period. “The period of undetectable viraemia lasted for a median of about one year but ranged from 0.3 months up to 13.5 years,” the investigators explain.

During this period, CD4 cell counts remained stable, but they began to fall by an average of 5 cells/mm³ per month after becoming detectable. “[This] is similar to that described in natural history during the first years following seroconversion,” the investigators comment.

Higher CD4 cell counts and the absence of seroconversion illness were linked to longer periods of undetectability.

The investigators explain that the ability of these patients to control HIV, at least temporarily, may help the development of new prevention and treatment strategies. “Insight into natural control might contribute to the development of new vaccines and therapeutics. More in-depth laboratory investigations are currently being undertaken in some of these patients,” they write.