This Week in HIV Research: Prevention and Treatment in the Real World

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Trying to gauge real-world relevance is one of the many challenging aspects of determining the value of published research, particularly when it comes to randomized drug trials. How much of a drug's efficacy rate in these trials is real, and how much is idealized? We poke at this question with some of the new research we've chosen to highlight this week, which includes:

  • Insight into the heavy impact of intimate partner violence (IPV) on a woman's desire to take pre-exposure prophylaxis (PrEP).
  • An updated look at HIV treatment failure rates among participants in prospective first-line therapy trials during this decade.
  • An exploration of the role that low-level viremia may play over time in a person's cumulative risk of virologic failure.
  • Additional nuance into our understanding of HIV drug levels in a mother's plasma relative to breast milk.

Of course, when you're done here, be sure to hop over to our ever-expanding coverage of last week's Conference on Retroviruses and Opportunistic Infections, a.k.a. CROI 2019; news of a potential second person cured of HIV may have grabbed headlines, but there was also plenty of research presented at the meeting with much more immediate clinical relevance. To beat HIV, you have to follow the science!

Barbara Jungwirth is a freelance writer and translator based in New York. Follow Barbara on Twitter: @reliabletran.

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

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Abuse History Factors Into Women's Attitudes Toward PrEP

Positive attitudes toward PrEP among social network members are often successful at encouraging women to try biomedical HIV prevention -- but not if those women have experienced IPV, a Connecticut prospective cohort study published in AIDS showed. The findings highlight a potential factor behind gender differences in PrEP uptake in the U.S.

Researchers surveyed 218 women eligible for PrEP, 94 of whom had experienced IPV. Participants were more likely to see themselves as candidates for PrEP if several members in their network also favored this HIV prevention method. However, this relationship did not also hold for women who experienced IPV, possibly because their networks were smaller and included fewer members who favor PrEP.

Women with abusive partners may be more concerned about their partner's reaction to their initiation of biomedical HIV prevention, study authors theorized. "Social network interventions might be one way to increase PrEP uptake among many US women but may not be as effective for women experiencing IPV," they concluded.

Prospective Data Offer Tempered View of HIV Treatment Success Rates

An updated, massive analysis of prospective first-line HIV treatment studies found that more than 20% of participants who initiated antiretroviral therapy in this decade failed treatment within 144 weeks, a rate much higher than generally seen in randomized trials, according to findings published in AIDS.

The new analysis updates prior research by including studies conducted between 2013 and 2017; in total, the database now comprises 181 studies and 77,999 participants spanning roughly 23 years.

The current examination focused specifically on individuals who started HIV treatment through a prospective study (believed to be a more accurate indication of "real-world" efficacy than individual, randomized trials) since 2010, exploring the frequency and correlates of failure after 48 weeks, 96 weeks, and 144 weeks.

Despite the sobering finding of overall failure rates still exceeding 20% in this decade, the researchers noted that efficacy is on the rise historically, and appears to be highest among the newest medications. Integrase inhibitor-based therapy, for instance, yielded a 48-week efficacy rate of about 88%, surpassing boosted protease inhibitor-based therapy (73%) and NNRTI-based therapy (71%).

In addition, most of the reported treatment failures in analyzed studies were due to people withdrawing or being lost to follow up, not an observed lack of efficacy. There was little data on why participants dropped out. Collecting standardized socioeconomic variables in clinical trials may help elucidate these reasons, study authors noted.

Based on cumulative efficacy data, the authors recommended that zidovudine (AZT, Retrovir) and efavirenz (Sustiva, Stocrin) no longer be listed as part of preferred first-line regimens for resource-limited settings; that there be greater promotion of genotyping before starting antiretroviral therapy; and that a clinical trial be conducted comparing emtricitabine (FTC, Emtriva) to lamivudine (3TC, Epivir) when either is taken in combination with tenofovir disoproxil fumarate and efavirenz. Furthermore, phase 4 studies should include longer follow-up periods and a four-drug initial regimen should be evaluated for people starting treatment at high viral loads, they advocated.

Residual Virus Increases Cumulative Viremia in Those on Successful Treatment

Residual virus may increase viremia over time even in successfully treated people living with HIV, a study published in AIDS found. That cumulative viremia risk is associated with a greater likelihood of eventual virologic failure, the study indicated.

Researchers calculated viremia copy-years – i.e., cumulative virus burden – over the course of 54 months for 850 people on HIV treatment who maintained a viral load below 200 copies/mL. The highest levels of viremia copy years were found in those with low-level viremia (viral load between 37 and 200 copies/mL) at baseline. A small but existent relationship was found between viremia copy-years and risk of virologic failure (hazard ratio 1.01; 95% confidence interval: 1.01-1.02).

Study authors noted that other studies had shown an association between cumulative HIV burden and mortality, but warned that the clinical relevance of their findings still needs to be determined. However, based on their findings, they suggested that virologic success for HIV treatment regimens be narrowly defined as "undetectable viremia."

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Adequate Plasma Drug Concentrations in Mother Important for Breastfeeding

Sufficient antiretroviral drug levels in the mother's blood are associated with a lower risk of HIV transmission during breastfeeding, a study in Malawi published in AIDS showed.

In the study, plasma concentrations of various HIV medications correlated substantially with breast milk concentrations, but not always in the same direction: Levels of zidovudine and lamivudine were higher in breast milk than in the mother's blood, while the reverse was true for nevirapine (Viramune), nelfinavir (Viracept), and lopinavir/ritonavir (Kaletra).

Women whose drug concentrations in blood were above the EC50 – the drug concentration that provides half the maximum response -- were less likely to have detectable HIV (odds ratio: 0.64) or transmit HIV via breast milk (hazard ratio: 0.40) than those with lower concentrations. Drug concentrations above EC50 in breast milk were also associated with lower likelihood of detectable HIV in the mother.

Because the cohort included only 27 women whose infants seroconverted during breastfeeding compared to 227 whose babies did not, no statistically significant conclusions could be drawn about the relationship between breast milk drug concentrations and HIV transmissions. Nonetheless, study authors called for the development of tools to help women adhere to their treatment regimen during pregnancy and breastfeeding.