Raltegravir/Truvada HIV PEP regimen well tolerated with no infections after its use

Raltegravir could have a “useful” role in HIV post-exposure prophylaxis, according to investigators from the US writing in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Doctors in Boston, Massachusetts, prescribed a post-exposure prophylaxis (PEP) regimen of raltegravir (Isentress) with tenofovir and FTC (Truvada) to 100 patients after possible sexual exposure to HIV.

None of the patients who returned for follow-up monitoring was infected with HIV. Side-effects were generally mild and were significantly less common, compared to PEP combinations based on a ritonavir-boosted protease inhibitor.

“The current study is the first to evaluate an integrase inhibitor, raltegravir, as the third active agent in a PEP regimen,” write the authors. “The rationale was based on findings that this drug has been shown to be extremely well tolerated, with potent antiretroviral activity.”

The use of PEP is recommended after some unprotected sexual encounters that could have involved exposure to HIV.

Generally, a three-drug regimen is prescribed consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and a ritonavir-boosted protease inhibitor. Treatment lasts for 28 days. Very few people have gone on to seroconvert for HIV after completing a course of PEP.

However, the side-effect profile of current PEP regimens could explain poor rates of adherence and treatment completion. A simple and well-tolerated regimen could therefore improve compliance, boosting the efficacy of therapy.

Truvada forms of the backbone of many HIV treatment combinations and has a generally mild side-effect profile. Raltegravir is less widely used, but has been shown to have a powerful anti-HIV effect with few side-effects.

Investigators from Fenway Health, a community clinic in Boston, designed a trial monitoring the use of these three drugs as PEP.

Between 2008 and 2010 a total of 100 people were prescribed the regimen after possible sexual exposure to HIV. Almost all (98%) were men, with the majority identifying as gay or bisexual. All the participants tested HIV-negative at baseline.

A little over a third of people (37%) accessed PEP after unprotected sex with a partner known to be HIV-positive.

The participants received a three-week course of standard-dose raltegravir (400 mg twice daily) and Truvada (one daily tablet combining 300mg tenofovir with 200 mg FTC). Adherence was measured using pill counts. People were asked to keep a diary recording side-effects.

A total of 85 people returned after three months for a follow-up HIV antibody test. None were positive.

The most commonly reported side-effects were nausea and vomiting (27%), diarrhoea (21%), headache (15%), fatigue (14%), and abdominal discomfort including bloating and flatulence (16%). In most cases, these side-effects were mild, and they resolved once therapy was completed.

The profile and prevalence of side-effects was similar to that observed at the clinic when a two-drug Truvada PEP regimen was prescribed.

Moreover, comparison with historic controls showed that the raltegravir/Truvada regimen was significantly better tolerated than triple-drug regimens based on a ritonavir-boosted protease inhibitor.

In total, 67% of people who completed their therapy took 100% of their doses. However, approximately a quarter of patients consistently missed their second a dose of raltegravir. All these patients reported adherence to their daily dose of Truvada,  as well as  the dose of raltegravir taken at the same time.

“Clinicians prescribing PEP might want to emphasise the importance of the second daily raltegravir dose as part of their initial counselling, and might use the conversation with their patients to think of strategies to enhance adherence to the second dose,” suggest the investigators.

They conclude, “This study was the first in humans to demonstrate that an integrase inhibitor can be well-tolerated as part of an HIV chemoprophylactic regimen...the lack of incident HIV infections and high level of tolerability was reassuring.”