Systematic review and meta-analysis of the effectiveness of Rifapentine plus isoniazid compared with isoniazid monotherapy in preventing active tuberculosis in HIV positive adults

Background

Tuberculosis is the highest cause of death in persons infected with HIV hence the need for prevention. The gold standard of self- administered isoniazid for 6 to 12 months is effective but adherence is poor and causes more adverse events. Rifapentine plus isoniazid for 3months administered under DOTS have limited treatment duration and may result in higher adherence and reduced adverse events.

Objectives

To determine the effectiveness of Rifapentine plus Isoniazid compared with isoniazid in preventing development of active TB in HIV infected adults.

Search methods

 Electronic searches were conducted in EMBASE from 1974 to June 27th 2014, Ovid MEDLINE In-Process and Other Non-Index Citations from 1946 to June 27th 2014, Science Citation Index searched for all times till June 27th and the Cochrane Central Register of Controlled Trials searched till 29th June 2014.Reference list of studies were also reviewed.

Selection criteria

RCTs of HIV positive adults treated with Rifapentine 900mg plus isoniazid 900mg (under DOTS or without DOTS) compared with 300mg of Self-administered isoniazid for 6 to 12months for prevention of active TB. Participants could be TST positive or negative from any setting, assessed for incidence of TB, drug resistance, drug adherence, drug completion rate, and adverse events.

Data collection and analysis

The author independently applied the eligibility criteria to identify studies, screen, assess methodological quality and abstracted data which was checked by a second reviewer.  The author pooled RR with their 95% CI using fixed-effect method.

Main results

Two RCTs with a total of 1056 randomised TST positive subjects were included and the median follow period was 35months.  RPT plus INH conferred similar efficacy as INH monotherapy (RR 0.95 CI; 0.54 to 1.65). All participants were TST positive. Hepatotoxicity was significantly reduced by 77% in the RPT plus INH arm compared to INH (RR 0.23 CI; 0.10 to 0.56). The risk of not completing a study drug was also reduced significantly by 71% for participants who received the combination drug (RR 0.29 CI; 0.21 to 0.41). Severe adverse effects were not different between the two groups (RR 0.84 CI; 0.53 to 1.34).  However, life-threatening or disabling effects was reduced significantly by 68% (RR 0.32 CI; 0.14 to 0.70) in participants who received the short course therapy. All the drug resistant cases occurred to INH. However, evidence was undermined by low number of events reported.

Authors’ conclusion

Rifapentine plus isoniazid is as good as IPT in preventing active TB in HIV infected adults. Hepatotoxicity which probably leads to drug discontinuation is reduced significantly with the newer regimen and treatment completion is also higher. Life-threatening adverse events are also less associated with the combination drug compared with isoniazid. Evidence suggests that a full cost effectiveness study is warranted.