It Is Possible to Develop Drug-Resistant HIV While on PrEP

A recently published study shows it is possible to develop a medication-resistant strain of HIV while on PrEP.

But it is unlikely, and the benefits of PrEP, or pre-exposure prophylaxis, drastically outweigh the risks of drug resistance, a doctor and a scientist who was not involved in the research wrote in an accompanying editorial.

Both pieces were published last month in the Journal of Infectious Diseases. Researchers led by Dara Lehman of the University of Washington analyzed plasma samples from subjects enrolled in the landmark PARTNERS study in Africa.

lab test

PARTNERS established the efficacy of PrEP using combinations of emtricitabine (FTC) plus tenofovir disoproxil fumarate (TDF), marketed as Truvada. The PARTNERS study also examined the use of TDF alone as PrEP.

The PARTNERS study looked at 4,747 heterosexual couples of mixed HIV status. Of those about 2,350 HIV-negative partners, 122 became infected with HIV over the course of one year. Of those, 58 had received a placebo instead of PrEP. Of the remaining 64, 25 received the medication now marketed as Truvada, a once-daily pill to prevent HIV. The other 39 were given TDF alone.

In total, five infected volunteers developed drug-resistant mutations. Upon further analysis, the researchers found that two of the five developed the mutation while taking PrEP, while three of them were already infected with HIV at the time they started PrEP.

Doctors know that anyone given PrEP who is already infected with HIV could develop medication-resistant mutations, but this study clarifies that the likelihood is low.

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Early HIV infections are known as acute infections. Although people may show flu-like symptoms a month or so after an HIV infection, the symptoms tend to be mild and pass within a week or so. Standard rapid HIV tests like those used in the PARTNERS study cannot always detect acute infections.

Lehman’s team used Abbot RealTime HIV-1 tests to detect HIV RNA in the archived plasma specimens obtained before “seroconversion,“ another term for becoming HIV positive. This allowed researchers to better determine when infections occurred.

Plasma samples were collected only every three months, however, though HIV antibody testing occurred monthly. So slight changes in the levels of medication found in samples could have occurred between these periods.

First Known Mutations in People Taking PrEP Regularly

The discovery of two people who developed a medication-resistant strain of HIV even though they were HIV-negative when they started PrEP and while apparently taking the medication as directed, is eye opening.

The research underscores several things about PrEP the medical community already knows. Dr. Robert Grant, who wrote the editorial alongside Lehman’s research, told Healthline that PrEP should still be taken as directed.

Grant is director of the Gladstone Laboratory of Clinical Virology at the University of California, San Francisco. He was named one of Time magazine’s most influential people in 2012 for being the father of “treatment as prevention.” He led the groundbreaking IPrEx study, which showed that treating people with HIV drastically reduces transmission of the virus as well.

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“I agree with the CDC guidance that the highest level of protection against rectal exposure to HIV is achieved after seven daily doses of Truvada PrEP. High-level protection for vaginal exposure comes after 20 days of daily use,” he said. “We have less information about when PrEP can be stopped.”

Some doctors have reported allowing clients to use PrEP intermittently before attending gay cruises or circuit parties. More information about the safety of this practice is expected Feb. 24 when the results of the IPERGAY study are released in Seattle.

“Continuing PrEP for 28 days after the end of the cruise, or party, is definitely enough — such is the equivalent of PEP (post-exposure prophylaxis) and provides coverage if the party mood continues onshore. Two to seven days of dosing after the last exposure might be enough if adherence prior to exposure was excellent,” Grant said. “The IPERGAY press release reported that ‘on demand’ PrEP with two tablets before sex and two tablets after sex provided some protection, but we do not yet know whether the level of protection was as high as we have seen with daily dosing.”

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For his part, Grant recommends sticking to the dosing recommended by the Food and Drug Administration (FDA) that “provides the highest level of protection, the most forgiveness for occasional missed doses, and fosters daily habit formation. Also, when there are side effects (which occur in about 10 percent of PrEP users), they typically occur in the first few weeks. Ideally, people would be beyond the start-up syndrome before the cruise.”

Honesty with PrEP Provider a Must

What are the important takeaways from this study?

First, PrEP needs to be taken as directed by the FDA. Patients need to tell their doctor if they have had a lapse in PrEP adherence and have put themselves at risk.

“Open communication is key,” Grant said. “If someone has been off PrEP for more than seven days and has a recent sexual exposure, they should start post-exposure prophylaxis (also known as PEP) urgently (within hours and before test results are back) using Truvada plus an integrase inhibitor. Then they can transition back to PrEP after a month.”

Open communication is key.
Dr. Robert Grant, UC San Francisco

Second, patients need to be honest with their doctor if they don’t feel well, especially before starting PrEP, to make sure they haven’t had a recent HIV exposure that traditional testing can’t detect.

Not only do PrEP consumers need to be honest, but doctors also need to be sure to ask, Lehman told Healthline.

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But why aren’t rapid HIV RNA tests available to find out right away, with better certainty, if someone is HIV positive? Standard tests may not show infections of up to 90 days prior.

“Rapid HIV tests have been developed and are working well in clinical settings outside of the United States,” Grant said. “The cost can be low, and the price will depend on market forces.”

He said the FDA process for approving HIV diagnostic tests is lengthy. Finding a way to expedite that process, as the FDA has already done for medications, is needed, Grant said.

For now, widely available HIV tests are good enough, he added.

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