The Infectious Diseases Society of America reported on June 29, 2018, that a new HIV acquisition had been found in a person using pre-exposure prophylaxis (PrEP).
According to the journal article, a 28-year-old cisgender male in Thailand began using PrEP on March 16, 2016, after being verified HIV negative by a third generation antibody test. He tested HIV negative again on a third generation antibody test on April 22, 2016. An RNA HIV test then revealed a positive result on May 13, 2016, and his viral load showed 116,187 copies on May 17, 2016. Dried blood spot and hair samples drawn on or around May 19 revealed daily adherence to PrEP for the previous six weeks.
The patient's strain of HIV showed an M184V mutation, suggesting resistance to emtricitabine (FTC or Emtriva, one of the two medications in Truvada). His genotype also showed A98G and K103N mutations, which suggest resistance to efavirenz (Sustiva, Stocrin) or efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) and that class of NNRTIs. At the same time, his strain did not have resistance to tenofovir disoproxil fumarate (Viread), the other medicine in Truvada. Despite the multi-level resistance, the patient successfully started on treatment medications, and his viral load decreased to undetectable levels by Aug. 3, 2016.
So, does this unique case demonstrate that PrEP is not as effective as was once believed? Is the "99%" number that many educators share too high?
Related: Has Anyone Gotten HIV When They Were on PrEP? (on TheBody)
Testing Protocols Not Followed
Not quite. Even if this were a case of daily PrEP failing to protect an individual from a resistant strain of HIV, it still would still be extremely unusual. With this case, to date, we have nine reports of individuals who seroconverted after initiating PrEP, and only two were able to verify adherence to PrEP at the time of seroconversion. In the event that all nine of these cases were due to the drug failing, that would still be less than 1% of the 315,000 or more people currently using PrEP to prevent HIV globally, according to data provided by Gilead Sciences Inc.
But this case brings up unique real-world challenges that others have not. The third generation antibody test available in this case has a window period of three to 12 weeks, with 3% of the population still testing HIV negative after 12 weeks. This is why clinical testing sites use RNA testing whenever possible, as the RNA test from May 13 did show positive for HIV while the third generation antibody test on the same day showed HIV negative.
The researchers acknowledge this limitation stating, "Nucleic acid testing (NAT) can definitively rule out HIV infection if performed with HIV antibody testing before PrEP initiation, but it was not available in this case." The RNA test is a nucleic acid assay (NAT or NAAT) blood test that detects HIV ribonucleic acid (RNA), the virus's genetic material, in about 10-14 days. This case illustrates how vitally important it is that all PrEP agencies have access to RNA testing, especially if they have patients that may have newly acquired HIV. If a provider can only offer antibody testing, then they face the risk of starting someone newly HIV positive on an incomplete medication regimen. And although RNA testing is commonplace in the U.S., this case shows that it is not readily available in health care settings in low and middle-income countries, illustrating global disparities in access to health care. Such medical inequities are antithetical to the goal of ending HIV as a global epidemic and demonstrate the need for better funding for PrEP agencies providing care internationally.
Is it possible that the third generation tests given on March 16 and April 22 missed an initial HIV acquisition that took place prior to starting PrEP? According to Robert Grant, M.D., principal investigator of the Iprex study and co-author of this journal report, "He might have been infected before he started [PrEP]. An RNA test was not done at that time." Grant added, "With some variation, PrEP may prolong the window period," referring to a newer journal report in June 2018 describing a case in which a new HIV diagnosis was delayed due to PrEP suppressing a patient's viral load.
David Malebranche, M.P.H., M.D. also shared his thoughts about the multiple scenarios presented in this case:
I don't know if one can conclude that it is a PrEP failure, especially since they weren't doing the fourth generation testing, just the antibody test. It's likely that the person was acutely seroconverting, in which case PrEP was not going to be effective. But it could be a [PrEP] failure because the virus they were exposed to was already resistant to emtricitabine. They mention the K103 mutation as well, which would make him resistant to Sustiva or Atripla and that class of NNRTIs. And the investigators said it is possible he was exposed during the first week of PrEP. So, in my eyes, its either he was exposed early on or right at the beginning of taking PrEP and the third generation antibody test was not picking up anything yet. Or he got exposed later on in his PrEP taking, but the virus he was exposed to just had multidrug resistance and Truvada wasn't going to protect no matter what.
It's unlikely we will ever have a complete answer to the conflicting scenarios Malebranche outlines. But, even with the unknown variables in this unique report, it is clear that PrEP continues to provide more than 99% protection for over 315,000 global consumers.
Malebranche added, "I think one of the overarching messages from this is that these are really rare occurrences -- but folks should be aware of them if they are planning to dip into a sexual pool where there is a high prevalence of HIV and possibility of various strains of resistance. No one wants to hear about people not getting HIV, they want to peddle fear and highlight the few who do get exposed."
Grant also pointed out how the PrEP regimen in this case helped to detect an early infection and suppress the patient's viral load within eight weeks: "Infection in the context of PrEP services has been extremely rare, and has led to early detection of viral infection, early use of combination antiretroviral therapy, and effective and prompt suppression of viral load."
Members of the PrEP Facts Facebook group come together every day (and night) to discuss fears about these rare events. Unfortunately, these real world cases often have gaps in information and reporting (such as what an RNA HIV test would have shown on March 16th, 2016) that make it difficult to precisely ascertain accurate timelines of HIV acquisition.
My hope is that health care consumers will consider the available facts and data that we do have and then make the sexual health decisions that allow them to experience greater connection, empowerment, and pleasure with others.