For maximum effect pre-exposure prophylaxis should be targeted to the subpopulations that account for the largest proportion of infections ( population-attributable fraction [ PAF ] ) and for whom the number needed to treat ( NNT ) to prevent infection is lowest.
It was estimated the PAF and NNT of participants in the iPrEx ( Pre-Exposure Prophylaxis Initiative ) trial.
The iPrEx study was a randomised controlled efficacy trial of pre-exposure prophylaxis with coformulated Tenofovir disoproxil fumarate and Emtricitabine ( Truvada ) in 2499 men who have sex with men and transgender women.
Participants aged 18 years or older who were male at birth were enrolled from 11 trial sites in Brazil, Ecuador, Peru, South Africa, Thailand, and the USA.
Participants were randomly assigned ( 1:1 ) to receive either a pill with active pre-exposure prophylaxis or placebo, taken daily.
Researchers have calculated the association between demographic and risk behaviour during screening and subsequent seroconversion among placebo recipients using a Poisson model, and they have calculated the PAF and NNT for risk behaviour subgroups.
Patients were enrolled during the period 2007-2009, and were followed up until Nov 21, 2010.
Of the 2499 men who have sex with men and transgender women in the iPrEx trial, 1251 were assigned to pre-exposure prophylaxis and 1248 to placebo.
83 of 1248 patients in the placebo group became infected with HIV during follow-up.
Participants reporting receptive anal intercourse without a condom seroconverted significantly more often than those reporting no anal sex without a condom ( adjusted hazard ratio, aHR=5.11 ).
The overall PAF for men who have sex with men and transgender women reporting receptive anal intercourse without a condom was 64% ( prevalence 60% ).
Most of this risk came from receptive anal intercourse without a condom with partners with unknown serostatus ( PAF 53%, prevalence 54%, aHR=4.76 ); by contrast, the PAF for receptive anal intercourse without a condom with an HIV-positive partner was 1% ( prevalence 1%, aHR=7.11 ).
The overall NNT per year for the cohort was 62. NNTs were lowest for men who have sex with men and transgender women self-reporting receptive anal intercourse without a condom ( NNT=36 ), Cocaine use ( 12 ), or a sexually transmitted infection ( 41 ). Having one partner and insertive anal sex without a condom had the highest NNTs ( 100 and 77, respectively ).
In conclusion, the pre-exposure prophylaxis may be most effective at a population level if targeted toward men who have sex with men and transgender women who report receptive anal intercourse without a condom, even if they perceive their partners to be HIV negative.
Substance use history and testing for sexually transmitted infections ( STIs ) should also inform individual decisions to start pre-exposure prophylaxis.
Consideration of the population-attributable fraction and number needed to treat can aid in discussion of the benefits and risks of pre-exposure prophylaxis with men who have sex with men and transgender women. ( Xagena )
Buchbinder SP et al, The Lancet Infectious Diseases 2014; 14: 468-475