PrEP injections every three months may protect against exposure from anal sex

Simon Collins, HIV i-Base

CROI 2014A new study presented at CROI 2014 by Chastity Andrews from the Aaron Diamond AIDS Research Centre and colleagues looked at defining protective drugs levels of GSK-744 needed to protect from multiple rectal exposures. [1]

Data in macaques has already reported that the investigational integrase inhibitor GSK744 is at least as effective as tenofovir when used as PrEP, and that this includes protection similar to sexual transmission from anal sex.

The promising potential for next generation PrEP has also been shown by pharmacokinetic data showing that the long-acting injection formulation of GSK744 has a sufficiently long half-life for the potential for injections to provide protection for as long as three months.

A group of 12 macaques were given a single GSK744 IM injection and exposed to SHIV weekly until infection occurred. Treated animals were protected for up to 7-16 exposures compared to 1-7 exposures for the control group.

Estimates for protective drug levels were calculated relative to the plasma GSK744 protein-adjusted IC90 (PAIC90) value. No infections occurred from the 59 challenges when plasma levels were more than three-fold higher than the PAIC90 (100% protection). This compared with 1 of 22 challenges when plasma levels were between 1-3 fold PAIC90 (97% protection) and 11 of 43 challenges when plasma levels were lower that the PAIC90. In placebo animals, 12 of 26 challenges resulted in infection.

No integrase-associated mutations were seen in infected animals at the time of infection, though longer follow-up will be important to confirm durability of this finding, given the long plasma half-life od GSK-744.

Importantly, similar drug levels in humans are achieved from a single 800 mg IM injection of GSK-744, suggesting that three-monthly injection may be achievable for future use as PrEP.

Similar levels of protection against vaginal exposure were presented in a pigtail macaques study presented by J. Gerardo Garcia-Lerma from the US CDC, Atlanta. This study reported protection results in six animals given GSK-744 with six controls, using monthly injections also detailed in a second late-breaker poster. [2, 3]


  1. Andrews CD et al. Correlating GSK1265744 plasma levels to prevention of rectal SHIV transmission in macaques. 21st CROI, 3-6 March 2014, Boston. Oral abstract 39.
  2. Garcia-Lerma JG et al. Monthly GSK744 long-acting injections protect macaques against repeated vaginal SHIV exposures. 21st CROI, 3-6 March 2014, Boston. Oral late breaker abstract 40LB and poster 941LB.
  3. Andrews CD et al. GSK1265744 long-acting protects macaques against repeated high-dose intravaginal challenges. Late breaker poster 941LB.

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