Raltegravir 800mg twice daily appears a good alternative to efavirenz for HIV-TB treatment

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Raltegravir seems to be a suitable alternative to efavirenz for HIV-TB co-infected patients while receiving TB treatment, according to 24-week results of the ANRS 12 180 REFLATE study presented at the Nineteenth International AIDS Conference (AIDS 2012) in Washington DC.

The phase 2 open label randomised trial aimed to estimate efficacy and safety of two doses of raltegravir and efavirenz for treatment of HIV and TB co-infected patients. 155 HIV-infected patients with confirmed or probable TB who were ARV naïve patients with a viral load of above 1000 copies/ml were randomised into three groups for the study.

The first group (n=52) received the standard World Health Organisation (WHO) regimen of 245mg tenofovir disoproxil, 300mg lamivudine (3TC) and 600mg efavirenz once daily. The second group (n=51) substituted the efavirenz for 400mg raltegravir twice a day , while the third group (n=52) were given 800mg raltegravir twice a day. All groups were given the standard first line treatment for TB containing rifampicin.

Glossary

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

concentration (of a drug)

The level of a drug in the blood or other body fluid or tissue.

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

63 % (95% CI 46-76) in the efavirenz regimen group reached the primary outcome of a viral load of less than 50 copies per ml at 20 and 24 weeks, compared to 76% (95%CI 65-88) in the 400mg raltegravir group and 78% (95%CI 67-90) in the 800mg raltegravir group. Meanwhile 76 % (95% CI 65-88) in the efavirenz regimen group reached the secondary outcome of a viral load of less than 400 copies per ml at 20 and 24 weeks, compared to 80% (95%CI 69-91) in the 400mg raltegravir group and 82% (95%CI 72-93) in the 800mg raltegravir group.

Virologic failure occurred in 15 (29%), 12 (24%), and 4 (8%) of the efavirenz, 400mg raltegravir and 800mg raltegravir groups respectively. Drug resistance was present in four cases of the efavirenz group, five of the raltegravir 400mg and one of the raltegravir 800mg groups in a subset available for resistance testing. The study was not designed to compare the groups directly so no test for significance was performed.

This study has important implication for the future use of efaverinz due to its potential limitations in terms of adverse events such as teratogenicity, cutaneous rash, central nervous system toxicity and transmitted drug resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). Raltegravir is of potential interest in HIV/TB coinfected patients due to drug interactions experienced between efavirenz and rifampicin. In prior pharmacokinetic studies, rifampicin reduced raltegravir concentration by about half, while doubling the raltegravir dose to 800 mg twice daily restored the concentrations to pre-rifampicin levels but the trough concentrations (Cmin) remained low.

48 week data and pharmacokinetic analyses are forthcoming.

References

De Castro N et al. A randomised trial to estimate efficacy and safety  of 2 doses of raltegravir and efavirenz for treatment of HIV-TB co-infected patients : ANRS 12 180 REFLATE TB trial. 19th International Conference on AIDS, abstract THLBB01 , Washington, DC, July 2012.

View the abstract on the conference website.

Download the Powerpoint presentation.

View the webcast on the conference website.