This Week in HIV Research: Exorcizing Our PrEP Demons

Executive Editor
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We've got a new group of studies to highlight this week that may well spur some soul-searching. If none of them do so, that's probably because you're already among the converted -- and if they do, consider sharing the findings with your colleagues, patients, and clients, to keep the conversation flowing.

There's a new reckoning underway in our thinking about some aspects of the continuing HIV epidemic, as evidenced by some of these featured papers:

  • A multidisciplinary group of experts pushes for normalization of pre-exposure prophylaxis (PrEP) in a major medical journal.
  • A new Centers for Disease Control (CDC) report finds that the vast preponderance of U.S. HIV transmissions occur among people with HIV who are not in care.
  • A Swiss study dives into potential factors associated with HIV drug resistance -- and finds that sociodemographic disadvantages may be at the core.
  • A real-world analysis of integrase inhibitor use among treatment-experienced people finds high success rates -- but only among those who had no baseline viremia.

Come along and free your spirit with a closer look at each of these peer-reviewed manuscripts. To beat HIV, you have to follow the science!

Myles Helfand is the executive editor and general manager of TheBody and TheBodyPRO. Follow Myles on Twitter: @MylesatTheBody.

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PrEP Should Be Normalized, Not Demonized, Experts Urge

The debate over whether PrEP usage leads to risk compensation -- increased risk-taking behavior as a result of feeling more protected from negative outcomes -- should not prevent clinicians from offering PrEP to all people at risk for HIV infection, according to a multidisciplinary team of authors writing in the New England Journal of Medicine.

The authors draw a parallel to the clinical discussion about oral contraceptives for women in the mid-1900s, stating that despite the concerns of some that hormonal contraceptive use would lead to sexual risk compensation, modern guidelines don't require people to commit to using condoms before being prescribed an oral contraceptive. They also advocate for the psychological benefits of improved sexual health as a result of PrEP uptake. "Disease prevention doesn't always trump other priorities for patients, for whom consistent condom use may not be realistic or desired," they write. "The same reasoning applies to PrEP."

The article is intended in part as a response to sentiments like those expressed in a June 2018 New York Times op-ed entitled "The End of Safe Gay Sex," said Julia Marcus, Ph.D., the lead author of the NEJM article, in an interview. Marcus was frustrated to read a perspective in mainstream media that was "moralizing PrEP and demonizing PrEP" -- and equally frustrated at "how persistent that is, even in scientific literature." The NEJM article's authors, a group that includes an HIV-focused epidemiologist, infectious disease physician, dermatologist, and clinical psychologist, counter that perceived bias with a call for normalizing PrEP across medical fields.

"[Contraception] was this really hard thing at the beginning -- lots of stigma, lots of questions about risk compensation -- and then it just became totally routine and totally normal," Marcus said. "If we can bring awareness of PrEP -- and routinize sexual history taking -- into primary care, this will go the way of contraception."

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Four of Every Five U.S. HIV Transmissions Happen When PWHIV Is out of Care

Most HIV transmissions in the U.S. can be traced back to a person with HIV (PWHIV) who is not currently receiving HIV care, according to a new data analysis led by CDC researchers and published in Morbidity and Mortality Weekly Report.

The new analysis is the result of the CDC effort to map U.S. HIV transmission rates along the HIV care continuum. Utilizing 2016 data, the researchers calculated an overall annual transmission rate of 3.5 per 100 person-years among people living with HIV -- but with wide variation in rates and total number of transmissions depending on where a person fell along the care continuum. Transmission risk broke down as follows (all rates are per 100 person-years):

  • Acutely infected, unaware of status: 4% of all transmissions; rate = 16.1.
  • Not acutely infected, unaware of status: 33.6% of all transmissions; rate = 8.4.
  • Aware of status, not in HIV care: 42.6% of all transmissions; rate = 6.6.
  • Aware of status, in care but viremic: 19.8% of all transmissions; rate = 6.1.
  • Aware of status, in care and undetectable: 0% of all transmissions; rate = 0.

The high contrast of transmission rate to number of transmissions for acutely infected people was due to the relatively small number of people in the U.S. who are newly infected but unaware of their status.

The researchers drove home the point that the study findings testify to the importance of early diagnosis and fast, sustained access to care for people living with HIV.

TheBodyPro has covered these findings in greater depth within a separate news article posted on March 21.

Demographic, Socioeconomic Factors Are Often Behind Acquired HIV Drug Resistance

Switzerland boasts very high virologic success rates -- and excellent overall access to quality health care -- among people living with HIV. But on the rare occasions when Swiss patients become resistant to their antiretroviral regimen, factors related to social disadvantage may often be to blame, according to a study recently published in Clinical Infectious Diseases.

The case-control study identified 115 participants in the massive, ongoing Swiss HIV Cohort Study who acquired a confirmed drug resistance mutation after initiating potent combination antiretroviral therapy. In an effort to tease out potential social factors underlying emergent resistance, the researchers went beyond the standard study-related patient documentation to explore medical charts, admission letters, hospitalization documents, indications of mental illness, potential language barriers, and evidence of coinfection treatment.

The researchers found that, among other factors, people who developed drug resistance were more likely than controls to:

  • Have been diagnosed with depression.
  • Have experienced mood swings, nightmares, or tiredness as a result of their antiretrovirals.
  • Be of African origin -- particularly if they were a migrant seeking asylum, had a language barrier, or were female.
  • Be unemployed -- especially if they also had a limited education, used injection drugs, or consumed alcohol in excess
  • Have been prescribed anti-infectives alongside their antiretrovirals, despite no apparent drug-drug interactions.

Acquired HIV drug resistance "is still of concern in the era of [combination antiretroviral therapy] in vulnerable patient groups that face a multitude of challenges," the authors conclude. "Multidisciplinary efforts are likely needed to help patients to overcome these significant barriers to adherence, and might include social services, counseling, or a referral to a psychiatrist."

Baseline Viremia Is Wildcard in Integrase Success Among Treatment-Experienced People

The efficacy of integrase inhibitor-based regimens demonstrated in clinical trials involving HIV treatment-experienced people has also been borne out among treatment-experienced patients in clinical settings, according to results from a prospective study published ahead of print in AIDS.

Researchers from the University of North Carolina-Chapel Hill recruited HIV treatment-experienced people who were naive to integrase inhibitors before commencing an integrase inhibitor-containing regimen between 2007 and 2016. The 773 patients included in the final analysis were relatively sexually diverse (43% were men who have sex with men; 32% were women) and racially diverse (59% were black); 42% had a detectable viral load at baseline.

Two years after switching to integrase inhibitor-based therapy, 95% of people who had an undetectable viral load at baseline were still virologically suppressed. Relatively speaking, virologic failure risk was lowest among people taking dolutegravir (Tivicay) and highest among people taking boosted raltegravir (Isentress).

By contrast, overall two-year virologic failure rates were high among patients who switched to an integrase inhibitor with a detectable baseline viral load, the authors wrote. They implied that poor adherence may be the cause. Unexpectedly, unboosted raltegravir (taken with two or more NRTIs) was associated with the lowest risk of failure among this subset of patients -- in fact, it was significantly lower than the risk seen among people taking elvitegravir (Vitekta) boosted with cobicistat (Tybost). The authors hypothesized that tolerance concerns related to cobicistat may be behind the difference, or that the twice-daily dosing of unboosted raltegravir may have resulted in a more forgiving regimen among patients who only partly adhered to treatment.

The study authors called for continued study of integrase inhibitor outcomes in clinical settings, and for more research exploring the relative efficacy of different integrase inhibitors -- especially in the setting of poor adherence or baseline drug resistance.