Out of an estimated 104,000 people offered HIV preexposure prophylaxis (PrEP) to protect themselves from HIV, just 14 people acquired a strain of HIV resistant only to the two drugs used in the HIV prevention pills.
"That to me was the most striking thing — how many people were on PrEP and how many got HIV," study author Urvi Parikh, PhD, GEMS co-director and associate professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, told Medscape Medical News. "People should feel reassured that PrEP is really effective and that people have been prevented from having HIV."
The early data, presented at the International AIDS Society (IAS) Conference 2021, are not the final word on HIV prevention drugs and the risk for breakthrough infection — or the risk of people acquiring drug-resistant HIV while using PrEP, she said. But it is among the first population-based studies to explore how common breakthrough infections are among people on PrEP, and it highlights how tricky it is for clinicians to know whether a case of HIV transmission while on PrEP is the result of poor drug adherence or drug-resistant strains of HIV circulating in the community.
Prior to this, fewer than a dozen cases of breakthrough HIV acquisition while on PrEP had been reported in the scientific literature worldwide. PrEP drugs have been approved for HIV prevention in the United States since 2012.
In the IAS-reported data, the Global Evaluation of Microbicide Sensitivity (GEMS) project worked with PrEP demonstration sites and government-run PrEP implementation programs in Kenya, South Africa, Zimbabwe, and Eswatini (formerly Swaziland) to gather information on people prescribed PrEP who acquired HIV. In total, about 104,000 people at all the sites were targeted for PrEP, and 229 acquired HIV.
That's an HIV acquisition rate of about 0.22%, assuming everyone who acquired HIV while on PrEP was captured by the study. For context, another study presented at IAS 2021 suggested that the background HIV acquisition rate for women in Africa was 2.2%. Taken together, the two studies suggest that PrEP may have effectively prevented 90% of HIV transmissions.
Of those 229 people who did acquire HIV, the investigators were able to include in their analysis drug-resistance test results for 118 people. More than half of those 118 people — 55% — had no drug-resistant mutations. That lack of mutations was most common among people who had low or no evidence of PrEP drugs in their systems, suggesting they had not used the pills before acquiring HIV.
Another 22% of participants had virus variants resistant to one of the four other HIV drug classes besides the ones that PrEP drugs fall into. That suggests, said Parikh, that the cases were completely unrelated to PrEP use or nonuse and were probably the result of transmitted drug resistance.
And then there were the 23% of participants who did have HIV variants with resistance to PrEP drugs tenofovir and emtricitabine. Of those, 28 participants had been highly adherent to taking their PrEP prescriptions on time, according to blood drug levels. Just 14 people had HIV variants that were resistant only to PrEP drugs and no other classes of HIV drugs, suggesting those cases could be directly the result of imperfect adherence.
But even that doesn’t confirm that those 14 cases of PrEP-only drug-resistant HIV acquisition were definitely the result of poor adherence to the pills. Last year, Matthew Spinelli, MD, an infectious disease doctor and researcher at the University of California, San Francisco, wrote a case report that was published in Clinical Infectious Diseases about a man who acquired HIV despite clinically validated high adherence to HIV PrEP. He too had PrEP-drug-resistant HIV.
Spinelli used blood tests and analyses of hair samples, which are used to measure PrEP adherence over time, to investigate what caused the HIV acquisition in the first place. He reported in Clinical Infectious Diseases that an odd combination of multiple HIV treatment-resistant mutations and evidence of high PrEP adherence suggested that the man hadn't acquired HIV because of poor PrEP adherence. Instead, it was most likely the result of the bad luck of taking PrEP drugs at the same time he was exposed to an HIV variant that was already resistant to the medications. So it wasn’t PrEP-related drug resistance at all.
This just goes to show, he said, that it's a mistake to use drug resistance as a reason not to prescribe PrEP. Instead, what people should be focusing on is the fact that out of an estimated 104,000 people, just 14 acquired a strain of HIV that was resistant only to PrEP drugs.
In light of recent news that insurers have 60 days to provide PrEP completely free with zero cost-sharing under the Affordable Care Act, Spinelli said people should be prescribing PrEP now more than ever.
"We need more PrEP," he said. "Otherwise. we're not going to beat HIV."
Latesha Elopre, MD, a PrEP provider and HIV clinician at the University of Alabama at Birmingham, has had three patients who started PrEP during the acute infection stage, before tests could detect it. None of the patients at her institution have acquired HIV while adherent to PrEP.
For Elopre, the new results don't change her desire to help her patients protect themselves from HIV with PrEP. What it does call for, she said, is consistent testing for HIV to catch new cases early and for clinics and systems to have referrals ready so everyone can practice status-neutral testing. Under that approach, testers explain that regardless of a patient's test result, there are treatment or prevention options: If the test is negative, they can take PrEP; if it's positive, Elopre can initiate rapid HIV treatment to keep their viral load undetectable and avoid ill health from untreated HIV.
"By no means do I think we should hold back PrEP from individuals," she said. But she said it does call for a conversation "informing them [that] if they were to seroconvert during this time, what that could mean for therapeutic options we have available to treat HIV. We have to allow patients to also have the autonomy to make a decision for themselves."
The study was funded by the United States Agency for International Development and the President’s Emergency Plan for AIDS Relief. Parikh and Spinelli report no relevant financial relationships. Elopre has received funding from Merck.
International AIDS Society (IAS) Conference 2021: Abstract 2585. Presented July 20, 2021.
Heather Boerner is a science and medical reporter based in Pittsburgh, PA and can be found on Twitter at @HeatherBoerner. Her book, Positively Negative: Love, Sex, and Science's Surprising Victory Over HIV, came out in 2014.
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Cite this: HIV Acquisition on PrEP Rare, Some Drug Resistance in First Large Study - Medscape - Jul 27, 2021.