Studies in humans

A few observational studies in humans have shown that the risk of infection is reduced by antiretroviral treatment. For example, one study found that a 28-day course of PEP with AZT (zidovudine, Retrovir) started within 24 hours of needlestick injury and exposure to HIV-containing blood could significantly reduce HIV infection rates.¹ Very few cases of HIV transmission have occurred after PEP, with only six reported transmissions worldwide in healthcare workers since 1997, despite PEP with two- or three-drug combinations.^{2 3 4 5}

One study found no seroconversions in victims of sexual assault who took PEP within 72 hours of exposure.⁶ Similarly, only one of 500 sexual assault victims in South Africa who were treated within 72 hours of the assault subsequently developed HIV infection.⁷

A 2005 study in San Francisco⁸ evaluated 702 male subjects who had taken PEP after sexual exposure (including some of the subjects enrolled in the study discussed above).  The evaluation took place 12 weeks after exposure. Three people seroconverted despite reporting no further sexual exposures after starting PEP, and so are probably evidence of PEP failure.  In addition, four people became HIV-positive despite PEP but there were either additional exposures to HIV or HIV was found in blood specimens given at the start of PEP (meaning subjects either sought PEP too late or were already infected with HIV and did not know it).

Of course, given that the chance of contracting HIV from a single occasion of receptive anal intercourse is in the region of one chance in 30 to one in 250, many of the men taking PEP would not have seroconverted anyway. Because of this, among 702 men one would only expect about six infections if they only had one risky encounter each. But because only three became infected who had definitely only had one encounter, the study implies that PEP prevents at least one in two infections.

The average time delay between the sexual exposure and taking PEP was 32.5 hours, but among men who became HIV-positive it was 45.5 hours – nearly two days – indicating that initiating PEP within a day of exposure ensures it has the best chance of working.

Researcher Michelle Roland said that the four men who went on to have unsafe sex soon after taking PEP were a reminder that it could not be a stand-alone prevention method: “It provides an important HIV prevention opportunity when exposed individuals may be especially receptive to assistance with reducing their HIV risk...but is only one part of that prevention activity. Sexual exposures are usually not isolated, and helping people stay HIV negative requires response to both the presenting exposure and attempts to reduce subsequent exposures.”

One of the more convincing studies⁹ was conducted in Brazil and reported at the Ninth Conference on Retroviruses and Opportunistic Infections (CROI). Here, 202 HIV-negative gay men were enrolled and followed for an average of two years. At the time of enrolment, 57% of the group reported 'high-risk behaviour'. PEP, consisting of four weeks of AZT/3TC, was used 100 times by 73 (36%) of the participants, 91% of whom completed the course. Most men took it just once or twice during the two years of the trial, but one man took it nine times.

There were eleven seroconversions among the group; however, only one occurred in someone who had taken PEP. Analysis of the strain of HIV that infected him despite using PEP showed that it had the M184V mutation (associated with resistance to 3TC).

The researchers calculated that PEP reduced the seroconversion rate by 83%, from 4.1 cases per 100 patients a year (among men who chose not to take PEP during the trial) to 0.7 cases in men who did take PEP.

However, the study also found that there was almost no difference in the infection rate observed in the study population as a whole (2.9 cases per 100 patients a year) and what would have been expected if PEP had not been available (3.1 infections per 100 patients a year). This was because PEP was not taken nearly often enough to make a difference to HIV incidence in the group as a whole. Although quite a high proportion of the study population took PEP, they were bad at evaluating risk and did not always take it when needed.

The reasons PEP was not taken were either that gay men mistakenly assumed their partner was faithful and HIV-negative, or that they became infected with HIV through routes they considered low risk, such as oral sex.

In this study, people were issued with ‘starter packs’ – ready-wrapped doses of AZT/3TC with instructions that participants should take them immediately following exposure. Other PEP schemes have relied on people reporting to A&E departments after weekend incidents. Since one of the key components to successful PEP is prompt treatment – ideally within 24 hours – this may explain some of the difference between the reported effectiveness rate of 83% in the Brazil study and the 53% rate reported in a previous cost-effectiveness study.¹⁰

PEP has been available in Denmark¹¹ since 1998, and the country operates a registry documenting every prescription. So far PEP has been prescribed 257 times, and to eleven individuals more than once. Only one seroconversion during PEP has been documented, of a gay man who later admitted to having risky sex again during the period he was on PEP.

Denmark’s guidelines state that PEP can only be prescribed within 24 hours of the risk incident, and the average length of time is only 10 hours (in the UK, where guidelines say it can be prescribed within 72 hours, the average waiting time is 23 hours).