Truvada/Kaletra HIV PEP combination is safe and effective with a low rate of discontinuations

A post-exposure prophylaxis (PEP) combination of FTC/tenofovir (Truvada) with lopinavir/ritonavir (Kaletra) tablets is safe and generally well-tolerated, French investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The researchers recommend that this combination should be the standard PEP regimen.

Few patients stopped taking their treatment because of side-effects. However, the investigators found that women were more likely to report gastrointestinal side-effects than men.

“Due to this good tolerability, the low discontinuation rate, the ease of use, TDF/FTC+LPV/r tablet formulation should be considered as the standard of care concerning HIV PEP”, comment the investigators.

In France – as in the United Kingdom and many other countries – the recommended treatment for both occupational and non-occupational PEP is two nucleoside reverse transcriptase inhibitors (NRTIs) and a ritonavir-boosted protease inhibitor.

Side-effects are one of the main reasons why patients fail to complete the recommended four weeks of therapy with PEP. It is therefore important to investigate which combinations are more tolerable.

Researchers therefore performed a prospective, observational study involving 249 patients who accessed PEP between November 2006 and June 2008. All these patients commenced treatment within 48 hours of their potential exposure to HIV. Most (82%) of the patients took PEP because of possible sexual exposure, and overall 60 of the source patients were known to be HIV-positive. A total of 23 patients had taken a previous course of PEP.

Blood tests were performed prior to the initiation of PEP to determine baseline full blood count, kidney and liver function, and lipid levels. These tests were repeated after 14 days and again after the completion of therapy on day 48. Patients were asked to report any side-effects they had experienced at these study visits.

However, 34 patients stopped treatment after it was established that the source individual was HIV-negative or because the possible exposure was considered to involve a very low risk of HIV transmission.

Of the 188 patients who should have completed PEP, a total of 22 stopped treatment because of side-effects. This included two patients with skin rashes and one individual with abnormal kidney function.

The other 166 patients completed therapy. The majority of these (96) said they had tolerated their treatment well. Moderate tolerability was reported by 59 individuals, and only eleven patients said that tolerability had been poor.

Complete adherence was reported by 70% of patients, with 27% telling investigators that they had missed one or two doses and 4% three or more doses.

A total of 92 patients reported side-effects. The most common were diarrhoea (78%), sleep problems (78%), nausea and vomiting (59%) and headache (38%).

Stomach problems and insomnia were more likely to be reported by women than men (p < 0.001 and p < 0.05 respectively).

Laboratory abnormalities were generally mild. The most common were elevated triglycerides (35%) or cholesterol (17%). Three patients had moderate increases in their phosphate levels, with three patients also having abnormal liver function, their ALT levels being moderately elevated.

Statistical analysis showed that women were significantly more likely to stop treatment because of side-effects than men (p < 0 .02) and to report poorer tolerability. Patients who had taken a previous course of PEP were more likely to discontinue therapy than those who were taking treatment for the first time (p < 0.03).

When the investigators limited their analysis to patients who were taking PEP following a possible sexual exposure to HIV, they found that gay men were less likely to discontinue therapy or report poor tolerability than heterosexuals (p <0.012 and p < 0.002 respectively).

Finally, the investigators compared the tolerability of this PEP regimen to those previous used in France. They found that the rate of discontinuation was significantly lower for patients taking the Truvada/Kaletra regimen.

None of the patients became infected with HIV.

“Female sex is associated with a higher risk of PEP interruption and with poorer tolerability”, comment the investigators, “these findings are important because a preventative treatment of these specific adverse events in this selected population could be necessary and help to increase HIV PEP completion rates.”

Nevertheless, the investigators recommend the Truvada/Kaletra combination as the standard of care for PEP, noting that there were significantly fewer discontinuations with this regime than with alternatives.

Tosini W et al. Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation. J Acquir Immune Defic Syndr, online edition, 2010.