HIV-test of sources with unknown status was performed in only 17 of 153 cases (11%). None were found HIV-positive. A total of 133 (87%) were not tested while data were missing in 3 cases (2%). The reasons for not testing were that the source was anonymous 66% (88/133), could not be contacted 5% (7/133), refused testing 6% (8/133), not attempted to test 3% (4/133), other reasons 2% (3/133), or missing data 17% (23/133). In 32 cases (9%), the patient had been raped. The HIV-status the assailant was unknown in 31 of 32 cases, while 1 assailant was known to be HIV-positive.
There was no significant difference in the proportion of PEP given to patients exposed to a source of unknown HIV-status or the proportion of patients who had had unprotected sex between each year of observation (χ2 test).
A total of 322 of 340 (95%) for whom the time from exposure to PEP was reported or could be estimated received PEP within 24 hours after the exposure. For cases where the exact time to initiation was indicated (n = 225), median time to initiation of PEP was 11.0 hours (range 0.5–60.0).
The number of PEP prescriptions increased over time, from 5 cases in 1998 to 87 cases in 2006 (Fig. 1). The relative proportion of PEP given to MSM is indicated. PEP was prescribed more than once to 23 patients (6%), 12 MSM and 10 heterosexuals (data on the sex of the source was not available in 1 case). Of the 23, 18 received PEP twice, 3 received PEP 3 times, and 2 received PEP 4 and 5 times, respectively.
Nine of 87 patients (10%) who received PEP in 2006, 6 MSM and 3 heterosexuals had received PEP previously. However, only 2 (2%) of these patients had had PEP more than once during that year.
PEP Regimen and Compliance
The initial PEP-regimens prescribed were zidovudine + lamivudine + lopinavir/ritonavir (52%), zidovudine + lamivudine + indinavir (35%), zidovudine + lamivudine + efavirenz (3%), zidovudine + lamivudine + nelfinavir (2%) or other regimens (7%).
PEP was completed by 65% (244/374), interrupted by 9% (35/374) while data on completion was missing in 25% of the cases (95). Of the 279 persons for whom compliance data were available, 87% completed PEP as planned. In 19 cases (7%) the regimen was changed during the 28 days treatment period among these were 3 cases of dose reductions.
The reasons for stopping PEP were a negative HIV-test of the source 29% (10/35), adverse effects in 40% (14/35), or other reasons 23% (8/35).
PEP was completed by 41% (13/32) of rape victims, interrupted by 13% (4/32) while data were missing for 47% (15/32).
Adverse Effects and Follow-Up
Adverse effects were experienced by 58% (218/374), whereas 17% (65/374) had no adverse effects and data were missing for 24% (91/374). Among 218 patients with adverse effects the majority had gastrointestinal complaints 85% (186/218), fatigue 34% (75/218), or headache 8% (18/218).
Only 51% (191/374) and 20% (75/374) complied with HIV-testing after 3 and 6 months respectively. Among rape victims only 34% (11/32) and 13% (4/32) were tested for HIV after 3 and 6 months, respectively. It is, however, possible that some of the patients have been tested elsewhere more convenient to them.
There was 1 case of seroconversion at 3-months follow-up. However, careful investigation revealed that this could not be attributed to PEP failure, but was probably due to repeated exposures during and after completion of PEP.
We found a steady but modest increase in the use of PEP over time to a maximum of 87 cases in 2006. From 2005 to 2006 there was a marked increase in PEP use especially among MSM. However, PEP was also used by a significant proportion of heterosexuals reflecting the distribution of sexual orientation in general among HIV-positives.15
In general PEP was given according to recommended guidelines. Among the 41% that were exposed to a source of unknown HIV-status, the majority had had high risk exposures typically receptive anal intercourse with a source belonging to a high risk group. The proportion of sources with unknown HIV status in countries where PEP can be prescribed by a wider range of physicians, was 73% in France,13 75% in Amsterdam,7 68% in Australia,6 and 57% in San Francisco.10
Our study demonstrate a PEP prescription practice that seems rational and targeted toward high risk exposures. However, an increased effort to test sources with unknown HIV-status would probably avert a significant number of PEP cases.17
Animal studies have shown that the time to initiation of PEP as well as duration of PEP is crucial for the preventive effect.3,4 Despite the fact that PEP is accessible only in few centers, the time to initiation of PEP was low as compared with other studies.6,7,10 One explanation can be a high degree of knowledge of PEP among Danish patients, especially MSM and discordant couples and health care workers as well as short distances to treatment centers. A Danish survey in 2006 among 3141 MSM found that 33% had practiced unsafe sex at least once within a year.18 Hence, the majority of MSM with potential HIV-exposure do not seek PEP. In a survey in 2000 75% of MSM were aware of the possibility of getting PEP after unsafe sex.19 This is higher than in many studies.20,21 A lack of knowledge about the possibility to get PEP does therefore not seem to be the cause. Accessibility to PEP does not seem to be a limitation either, since the time to initiation of PEP was relatively short. It is possible, that the majority of persons practising unsafe sex take a calculated risk, while the persons that requests PEP either as an exception had had unsafe sex or a condom tear or have obtained knowledge or suspicion that the source is HIV-positive. The frequency of repeated PEP courses were comparable with a recent study from Amsterdam7 but low compared with studies from Australia6 (14% in 5½ year) and San Francisco22 (17% in a year).
The rate of completion of PEP among participants was comparable with what has been found in other studies.6,13 It is worrisome, however, that a substantial proportion of the patients failed to complete the PEP treatment. Studies investigating the reasons behind and modes to improve this are needed. The proportion of rape cases that completed PEP was low as seen by others23,24 and in accordance with previous Danish data.25
It is noteworthy, that while our findings are relevant to the situation in most western countries, they are not directly applicable to the situation in high prevalence countries. Many western countries are characterized by a low background HIV prevalence, a population that is well educated, easy access to health care and access to PEP after HIV exposure through consensual sex as well as following rape.26,27 Given the low background prevalence of HIV it is very important to ensure a careful and rational risk assessment to avoid a high degree of unnecessary treatment.
In contrast, in a high HIV prevalence like South Africa PEP is, apart from occupational exposure, almost exclusively offered to rape victims.28,29 These patients are very vulnerable in many ways, often minors, and are often likely to present late. The risk of HIV transmission even in the absence of knowledge of the assailants HIV-status is so high that PEP is justified in any case. Giving PEP in these conditions is far more challenging but studies have shown that with the right approach it is possible to obtain a reasonable rate of compliance and time to initiation.29
There are some limitations in our study that need to be considered. The retrospective nature of a large part of the data as well as a high percentage of missing data are important to consider when interpreting the results. Efforts should be made to improve compliance with follow-up and to collect data on follow-up when this is done in other settings. We unfortunately do not have data on the total number of requests for PEP or the reasons to decline PEP.
In conclusion this nationwide study showed a steady but moderate increase in the use of PEP following sexual HIV-exposure from 1998 to 2006. Time to initiation of PEP was low and the PEP prescription practice was targeted toward high risk exposures.
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