Suprising differences in PREP effectiveness in men and women

[Cosmicdancer]

A couple of studies of PREP in women found that adherence rates of 29% and 36% were not sufficient to protect them from HIV.  Women need to take PREP daily in order to prevent infection via vaginal sex.  For men, however, they found that taking PREP 2 days per week was sufficient to prevent infection via anal sex.  This seems really counter-intuitive so I'd love to see more data on this.  I do recall that the large PREP Partners Trial involved over 4,700 heterosexual couples, and the efficacy of Truvada was 62% in women despite high adherence rates.  The iPREP study of gay men found 100% protection if they took it at least 4 days per week, so the different modes of transmission (vaginal vs. anal) does help explain why the different studies had different results.

Model explains why HIV prevention dosing differs by sex

Date: October 30, 2014
Source: NIH/National Institute of Allergy and Infectious Diseases
Summary: A mathematical model predicts that women must take the antiretroviral medication Truvada daily to prevent HIV infection via vaginal sex, whereas just two doses per week can protect men from HIV infection via anal sex. This finding helps explain why two large clinical trials testing HIV pre-exposure prophylaxis, or PrEP, in women failed to show efficacy.

A mathematical model developed by NIH grantees predicts that women must take the antiretroviral medication Truvada daily to prevent HIV infection via vaginal sex, whereas just two doses per week can protect men from HIV infection via anal sex. This finding helps explain why two large clinical trials testing HIV pre-exposure prophylaxis, or PrEP, in women failed to show efficacy. Participants in the VOICE and FEM-PrEP trials of Truvada and tenofovir (another antiretroviral) for HIV prevention were counseled to take one of the medications daily. However, because they actually took the antiretroviral only about 29 percent of the time in VOICE and about 36 percent of the time in FEM-PrEP, the PrEP strategy did not work.

Angela D. M. Kashuba, Pharm.D., of the University of North Carolina, and colleagues determined what intracellular ratios of active tenofovir and emtricitabine, the drugs that compose Truvada, to the DNA molecules with which they compete are necessary to prevent HIV replication. Next, using data from an early clinical trial in women, the researchers created a mathematical model that predicts these ratios in vaginal, cervical and rectal tissues given standard doses of medication taken 2 to 7 days per week. Then, the scientists calculated the percentage of a study population that would achieve the effective drug-to-DNA-molecule ratio by taking tenofovir or Truvada at each dosing frequency.

The model forecasts that two standard doses per week of Truvada or a daily standard dose of tenofovir would achieve the target ratio in rectal tissue across a study population. A daily standard dose of Truvada would achieve the target ratio in vaginal tissue in more than 75 percent of a study population, according to the model, and in cervical tissue in half of the population. A daily standard dose of tenofovir would achieve the target ratio in cervical and vaginal tissues in less than half of a study population, the model predicts.

It is easier to achieve the target ratio in rectal tissue than in cervical and vaginal tissues, according to the scientists, because the concentration of DNA molecules is lower and of tenofovir is higher in rectal tissue than in the female genital tract.
Both men and women who are prescribed Truvada for PrEP should take the pill daily as directed, according to Centers for Disease Control and Prevention guidelines.

http://www.sciencedaily.com/releases/2014/10/141030101547.htm

[tryingtostay]

I would of guessed it's easier to achieve this because the colon has a high amount of blood vessels.  I never educated myself too much on the vagge.  Alright, no wise cracks about this, hah

[AusShep]

The data us really good to know, but I've never understood such poor adherence. 

I mean who at likely substantial risk for HIV, and in a study to prevent it, only remembers to take their meds once every 3 or 4 days...?

[Jeff G]

The data us really good to know, but I've never understood such poor adherence. 

I mean who at likely substantial risk for HIV, and in a study to prevent it, only remembers to take their meds once every 3 or 4 days...?

Well ... we see HIV positive people that are not adherent all the time so go figure .

[AusShep]

Well ... we see HIV positive people that are not adherent all the time so go figure .

Yeah, it is pretty bad when all is said and done that only 28% of poz in the US are in care, on meds, and UD...

Just seems if you're in a study you'd be part of the 40% on meds and committed to it, but maybe they get money for participation or something...

[tryingtostay]

Crazy how that was even a study.  Risking HIV contraction. 

[buginme2]

Two days per week effectiveness in men is great.

A little party pack for the weekend with two truvada pills.