This Week in HIV Research: From PrEP to Treatment, There's Always More to Learn

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Jeremy Webster for Hemera via Thinkstock

For all of us who work in an HIV-relevant field, the learning never ends. Science is an ocean, and we're constantly feeding it with rivers of new research.

Once you've read through this week's selection of recently published HIV-related studies, you'll know a little more than you did yesterday about:

  • The promise of lamivudine/raltegravir as a future pre-exposure prophylaxis (PrEP) option.
  • The potential impact of a feminizing hormone on PrEP efficacy.
  • The gentler renal profile of new tenofovir (TAF) compared to old tenofovir (TDF).
  • The role internet dating plays in HIV incidence.

Come aboard and sail the research-driven seas with us. 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.

Lamivudine/Raltegravir as PrEP: Rectum vs. Vagina

Raltegravir plus lamivudine warrants further study as an alternative for PrEP, phase 2 study results presented at the 25th Conference of the British HIV Association suggested.

Thirty-six volunteers, half of whom are women, were randomized to start with seven days of either a lamivudine/raltegravir (Dutrebis) combination or raltegravir (Isentress) only. After a month-long washout, the drug assignment was reversed for another seven days. Each volunteer had two tissue biopsies, but these were staggered to obtain data at different time points.

For the first time in pharmacodynamic research, rectal tissue was taken from women, presenter Julie Fox, M.D., noted. When levels of the two drugs were measured separately from each other, each showed higher concentrations in rectal tissue relative to vaginal tissue. In vaginal tissue, lamivudine levels exceeded raltegravir levels. When the drugs were combined, rectal samples showed 100% protection from HIV after two days, while vaginal biopsies took eight days to reach 100% protection.

That difference is similar to studies of tenofovir/emtricitabine (Truvada), the currently used PrEP drug, noted an aidsmap report. It concluded that lamivudine/raltegravir PrEP could work on an as-needed basis in men, but would need to be taken daily by women.


Estradiol May Lower TDF/FTC PrEP Efficacy, Small Study Finds

Speaking of noteworthy rectal drug concentrations: The rectal tissue of transgender women taking feminizing hormones contained a lower ratio of PrEP metabolites to competing deoxynucleotides than did the tissue of cisgender participants, a small study published in Clinical Infectious Diseases found.

The ratio of tenofovir-diphosphate (TFVdp) to deoxyadenosine-triphosphate (dATP) is important for PrEP potency. Researchers compared this ratio in 12 volunteers taking tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada) for HIV treatment or PrEP. Participants included transgender women taking estradiol, cisgender men, and postmenopausal cisgender women.

The more estradiol a trans woman used, the lower her TFVdp:dATP ratio -- i.e., the less TFVdp compared to dATP -- in her rectum. In blood plasma, there was no difference in ratio among the groups.

The iFACT study had shown lower blood levels of tenofovir in trans women taking hormones, but concluded that this could be due to low adherence rather than a drug interaction. Authors of the current study called for further research into the clinical implications of their findings, but meanwhile cautioned that "FHT [feminizing hormone therapy] may negatively impact PrEP efficacy."

TAF's Better Renal Safety Confirmed

An analysis of pooled data from 26 trials that was published in AIDS theorized that tenofovir alafenamide's (TAF) much lower blood levels of tenofovir compared to tenofovir disoproxil fumarate (TDF) may be related to the newer drug's better renal profile.

The analysis included data on 9,322 children and adults with a cumulative exposure of 12,519 person-years to TAF and 5,947 person-years to TDF. Both treatment-naive participants and those switching to TAF from a TDF-based regimen were included.

Ten cases of proximal renal tubulopathy -- when the kidneys do not properly filter urine -- were reported among the 2,962 participants taking TDF, but none in the TAF group. Similarly, 14 participants on TDF discontinued a study due to adverse events involving the kidneys, but only three of those taking TAF did so.

The study authors noted that boosting agents increase tenofovir concentrations, which may heighten the risk of kidney problems in those taking TDF. "These data support a comparative renal safety advantage of TAF over TDF in a broad range of [people living with HIV]," they concluded.

Internet Dating Not Linked to More HIV Transmissions

Internet dating among men who have sex with men (MSM) is not associated with a higher risk of seroconversion or a wider geographical spread of the virus, a study published in Clinical Infectious Diseases showed.

Researchers followed 147 MSM who were diagnosed with acute or early HIV infection for a year. A detailed questionnaire at baseline established sexual activity and internet partner seeking behavior. Genetic network analysis was performed for the 20 associated seroconversions during the study period.

Participants who looked for partners online were more likely to have a greater number of sexual partners, but they were no more likely to be associated with HIV transmissions than those who found their partners in real life. The HIV clusters were not spread out further geographically in the online versus the offline group.

These results may be due to disclosure of serostatus on dating apps and serosorting or increasing use of PrEP, study authors hypothesized. They also noted that their questionnaire did not differentiate among the various types of dating websites and apps and called for future studies to do so to help target risk-reduction programs.