PrEP delays HIV detection in seroconverters but does not boost resistance risk

By Marilynn Larkin

NEW YORK (Reuters Health) - Continuing pre-exposure prophylaxis (PrEP) in HIV seroconverters may delay HIV infection detection but does not increase the risk of drug resistance, researchers report.

PrEP has been shown to substantially reduce the risk of HIV acquisition with good adherence, although the strategy requires frequent HIV testing to detect acute/early infection and minimize risk of resistance, according to Dr. Deborah Donnell of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues.

For those who acquire HIV in spite of PrEP, whether continued PrEP use changes the progression of seroconversion or the natural evolution of HIV was not known.

To investigate, Dr. Donnell and colleagues retrospectively analyzed the pattern and timing of HIV seroconversion among participants in the Partners PrEP Study, a randomized, placebo-controlled trial conducted in Kenya and Uganda.

Participants were seen monthly for HIV testing and given a month’s supply of study medication. Those with reactive or discordant rapid tests were considered possible seroconverters, and confirmed by third generation EIA at the local laboratory. Plasma and serum samples were stored at months one, three and each subsequent quarterly visit, at any visit with a reactive HIV-1 test, and for seroconverters, at visits within a month and then quarterly thereafter. HIV-1 infections were confirmed centrally from stored samples.

Study drug was temporarily stopped for HIV-reactive tests and permanently stopped when seroconversion was confirmed.

The time to detection of HIV infection was measured from the time of a sample with evidence of infection to the time of detection of seroconversion. The analysis of time to Fiebig stage (http://go.nature.com/2uFN36i) was based on all samples available during the seroconversion period, defined as from the last visit without HIV infection to when Fiebig stage six (early chronic infection) was first reached.

A delay in detection of seroconversion was defined as more than 100 days between the first HIV infected sample and detection of infection at the local study center.

As reported online July 7 in AIDS, among 138 seroconverters (about half men, median age 30), 71 had been assigned to the placebo group and 67 had been assigned to PrEP, including 40 who received TDF (tenofovir disoproxil fumerate) and 27 who received FTC/TDF (emtricitabine/ tenofovir disoproxil fumerate).

Fifteen of the seroconverters were HIV infected (HIV-1 RNA detected) but seronegative at initial randomization; 111 became infected during the study; nine were infected during an off-study drug period; and three were infected at placebo re-randomization (which took place after the independent data monitoring committee recommended that use of placebo be discontinued).

PrEP was associated with a significant increase in delayed detection of infection (OR=3.49, p=0.044). A delay in detection, however, was not associated with increased risk of resistance among those who took PrEP (OR=0.93, p=0.95).

The estimated time to each Fiebig stage was longer in seroconverters who continued on PrEP, with a significant elongation to stage 5 (28 days versus 17 days, p=0.05). After adjustment for Fiebig stage, viral RNA was approximately 2/3 log lower in those assigned to PrEP compared with placebo. No differences were found in Architect S/CO (signal-to-cutoff ratio; a measure of HIV antibody response) at any stage.

Dr. Donnell told Reuters Health, “Like an early treatment intervention, PrEP suppressed HIV viral load during seroconversion. This may ultimately be good for the patient.”

“We do need to use highly sensitive rapid HIV-1 tests in patients using PrEP so that delays in developing a full antibody response will not delay detection of HIV-1 infection,” she said by email.

“It is so encouraging to see the beginning of PrEP scale up in people at risk for HIV in the US and globally because we know there is a huge potential benefit for PrEP in preventing HIV infection,” she concluded.

Dr. Antonio Urbina of Icahn School of Medicine at Mount Sinai in New York City, said, “This study is reassuring in showing that rates of drug resistance do not increase in patients who continue on PrEP during seroconversion.”

“And importantly,” he told Reuters Health, “viral load levels for seroconverters on PrEP versus placebo were up to 1,000 x lower, implying that patients who remain on PrEP would be significantly less infectious and hence less likely to transmit.”

“Current guidelines recommend immediately discontinuing TDF/FTC once HIV is detected,” he said by email. “But this study suggests that perhaps continuing - with intensification of therapy - may be a better strategy for seroconverters with good adherence to PrEP.”

SOURCE: http://bit.ly/2tcUBJb

AIDS 2017.

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