Post-exposure prophylaxis (PEP) regimens consisting of tenofovir/emtricitabine (Truvada) plus lopinavir/ritonavir (Kaletra) or raltegravir (Isentress) prevent HIV infection as well as zidovudine/lamivudine (Combivir) regimens, but with fewer side effects, according to 2 presentations at the recent 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) in Cape Town, South Africa.

PEP refers to antiretroviral therapy (ART) taken as soon as possible -- within 48 to 72 hours -- after occupational (e.g., accidental needle-stick) or non-occupational (e.g., broken condom) exposure to HIV. Regimens containing zidovudine (AZT; Retrovir) have often been used for this purpose and are the most extensively studied.

Currently non-occupational PEP guidelines recommend efavirenz (Sustiva) plus either zidovudine/lamivudine or tenofovir/emtricitabine as preferred NNRTI-based regimens, and lopinavir/ritonavir plus zidovudine/lamivudine as a preferred protease inhibitor-based regimen. Occupational PEP guidelines are more complex, varying according to extent of exposure and other factors.

Tenofovir/emtricitabine plus Lopinavir/ritonavir

Since 1998, Christian Rabaud and colleagues have evaluated the tolerability of 3 PEP regimens used in France: zidovudine/lamivudine plus nelfinavir (Viracept) twice-daily, zidovudine/lamivudine plus lopinavir/ritonavir soft-gel twice-daily, and tenofovir/lamivudine plus ritonavir-boosted atazanavir (Reyataz) once-daily. More recently, they added tenofovir/emtricitabine plus lopinavir/ritonavir tablets.

Between November 2006 and June 2008, a total of 249 people at 10 French hospitals were included in the study; 16% had occupational exposures, 82% had sexual exposures, and 2% had other types of exposures.

Of the patients who started PEP, 11% were lost to follow-up and 14% stopped therapy for reasons other than adverse events (including the source patient testing HIV negative). About 9% discontinued before Day 28 (median treatment period 7 days) due to adverse events, including 2 cases of skin rash, 1 case of kidney stones, and 1 case of rhabdomyolysis (muscle damage).

None of the study participants experienced HIV seroconversion indicating established infection. Among the 166 people (67%) who completed the full 28-day PEP regimen, 58% reported good tolerability, 35% reported moderate tolerability, and 7% reported poor tolerability. Among patients who experienced at least 1 side effect, 78% reported diarrhea, 78% asthenia (weakness), and 59% nausea or vomiting.

The researchers concluded that the rate of PEP discontinuation due to adverse events "appeared significantly lower" among patients taking tenofovir/emtricitabine plus lopinavir/ritonavir compared with the other 3 regimens.

Groupe d'Etude sur le Risque d'exposition des Soignants aux Agents Infectieux (GERES), Paris, France; Hopital Bichat-Claude Bernard, Paris, France; Hôpital Beauregard, Thionville, France; Centre Hospitalier Régional, Orléans, France; Hôpital Sainte Marguerite, Marseille, France; Centre Hospitalier Régional, Metz, France; Hôpital Bicêtre, Paris, France; COREVIH Lorraine Champagne Ardenne, France; Centre Hospitalier et Universitaire, Nancy, France.

Tenofovir/emtricitabine plus Raltegravir

The second study was presented by Kenneth Mayer from Fenway Community Health Center in Boston, which has been studying non-occupational PEP since 1997. In 2008, the center began evaluating tenofovir/emtricitabine plus the integrase inhibitor raltegravir. In addition to being well-tolerated when used for treatment of chronic HIV infection, raltegravir acts at an earlier stage of the HIV lifecycle than protease inhibitors.

The first 51 patients treated with this regimen were all men and most were gay or bisexual. About half each reported unprotected receptive anal intercourse and unprotected insertive anal intercourse as routes of exposure (a majority also reported unprotected oral sex); about 60% had sex with a partner known to be HIV positive.

About 60% of the study participants completed the 28-day raltegravir PEP regimen (compared with about 40% of patients using zidovudine/lamivudine plus a protease inhibitor) and more than half reported complete adherence. Again, none became HIV positive. Only 2 participants discontinued therapy due to adverse events.

No significant kidney, liver, or hematological (blood) abnormalities were reported. The most common adverse events were nausea, diarrhea, and fatigue. Men using the raltegravir regimen reported significantly less diarrhea (29% vs 59%), nausea or vomiting (31% vs 59%), and fatigue (10% vs 49%) than those who used zidovudine/lamivudine plus a protease inhibitor, but were more likely to report abdominal pain, bloating, or gas (18% vs 3%).

The investigators concluded that tenofovir/emtricitabine plus raltegravir was generally well-tolerated for non-occupational PEP and had a good safety profile.

Fenway Health, Fenway Institute, Boston, MA; Brown University, Infectious Disease Division, Providence, RI; Harvard Medical School, Boston, MA.

9/11/09

References

W Tosini, P Muller, T Prazuck, and others. Tolerability of post-exposure prophylaxis (PEP) of HIV infection with the combination of tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation (Truvada + Kaletra). 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WEAC102.

K Mayer, M Mimiaga, M Gelman, and others. Tenofovir DF/emtricitabine/ raltegravir (TDF/FTC/RAL) appears safe and well-tolerated for non-occupational post-exposure prophylaxis (NPEP). 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WEAC104.

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