Drug efficacy by direct and adjusted indirect comparison to placebo: An illustration by Mycobacterium avium complex prophylaxis in HIV

Table 1 Characteristics of 5 randomized controlled trials of primary prophylaxis against Mycobacterium avium complex in HIV-infected adults

Study	Drug dose	No. subjects	Mean CD4 Count ^a (cells/μl)	% On ART	Median Follow-up time ^b (days)	Primary MAC events (N)	Direct monthly failure rate (95% CI)	Direct monthly probability of failure
Nightingale 1993, study 023 and 027^c[13]	Rifabutin, 300 mg, qd	283	64	100	209 ^d	24	0.012 (0.007-0.017)	0.012
	Placebo	290	56	100	202 ^d	51	0.027 (0.019-0.0034)	0.026
Havlir 1996[17]	Rifabutin, 300 mg, qd	223	47	--	514	52	0.014 (0.010-0.018)	0.014
	Azithromycin, 1200 mg, qwk	223	49	--	514	31	0.008 (0.005-0.011)	0.008
Benson 2000[16]	Rifabutin, 300 ^e mg, qd	391	30	75	574	59	0.008 (0.006-0.010)	0.008
	Clarithromycin, 500 mg, bid	398	27	73	595	36	0.005 (0.003-0.006)	0.005
Pierce 1996[14]	Clarithromycin, 500 mg, bid	333	30	--	427 ^f	19	0.004 (0.002-0.006)	0.004
	Placebo	334	25	--	402 ^f	53	0.012 (0.009-0.015)	0.012
Oldfield 1998[15]	Azithromycin, 1200 mg, qwk	85	44	--	400 ^d	9 ^g	0.008 (0.003-0.013)	0.008
	Placebo	89	44	--	340 ^d	24 ^g	0.024 (0.015-0.034)	0.024

qd: once a day; bid: twice a day; qwk: once a week; MAC: Mycobacterium avium complex; ART: antiretroviral therapy; CI: confidence interval
^a At baseline
^b All patients on ART were on dual or mono therapy
^c Study 023 and 027 are two identically designed studies. We calculated weighted averages the number of subjects, follow-up time, and number of new MAC events for the two studies.
^d Duration on treatment
^e This study was originally designed with a 450 mg qd dosage but reduced to 300 mg qd after 9 months.
^f Mean follow-up time
^g The primary endpoints of this study were MAC symptoms and positive culture. We only included culture-positive events, to remain consistent with the other studies, which all used positive MAC cultures as primary endpoints.

ISSN: 1742-6405