Timing of Antiretroviral Therapy for HIV in the Setting of TB Treatment

Table 1

Studies on initiation of highly active antiretroviral therapy (HAART) in HIV/TB-coinfected individuals.

Study (author, year)	Study characteristics	Timing of HAART relative to TB treatment	Outcomes	Adverse events
Leonard  et  al.  2002 [51]	- Retrospective cohort; - 644 adults and children (60% pulmonary TB, 25% pulmonary and extrapulmonary TB, 15% extrapulmonary TB); - Single center — Atlanta, GA; - Comparison of 3 HIV/TB coinfected cohorts: 1991, 1994, 1997	HAART at time of diagnosis versus HAART post-TB diagnosis — not defined	Decreased 1 year mortality in 1994 and 1997 cohort compared to 1991 cohort	N/A
Sungkanuparph et  al.  2006 [52]	- Retrospective, observational; - 29 adult patients (69% pulmonary TB, 31% extrapulmonary TB); - Jan 2002–Dec 2002; - Single center—Thailand	Median 8 weeks (range 4–12 weeks)	Virological suppression; -65% at 24 weeks; -76% at 48 weeks; TB outcomes; -26/29 completed therapy; -No relapse; -No new OI	IRIS—1/29; Death—1/29 (CMV encephalitis); Rash—2/29 (NVP); EFV switched to NVP 1/29 (dizziness); AZT switched to D4T 3/29 (anemia)
Manosuthi  et  al. 2006  [53]	- Retrospective cohort; - 1003 adult patients; - Jan 2000–Dec 2004; - Single center — Thailand; - Comparison of HAART+ to HAART− group	2 mth versus 4 mth versus; 6 mth versus 9 mth versus; 12 mth (subgroup analysis)	Increased survival for pts. receiving HAART as compared to no HAART; Increased mortality with HAART initiation at >6 mths. (11.3%) compared to <6 mths (4.1%) (𝑃=.018)	N/A
Sanguanwongse  et al. 2008 [54]	- Observational cohort; - 1269 patients (adult and pediatric) (54% pulmonary TB, 35% extrapulmonary TB, 12% both); - Oct 2004–March 2006; - Multicenter — Thailand National Surveillance Network	Not defined	Decreased mortality in group receiving HAART (11%) compared to that not receiving HAART (46%) (relative risk 0.24, 95% confidence interval: 0.19 to 0.30)	N/A
Tabarsi  et  al.  2009 [55]	- Retrospective cohort; - 69 patients; - 2002–2006	Group I: HAART after 8 wks if CD4 < 100; Group II: HAART at 2 wks if CD4 < 100; Group I & II: HAART after 8 wk if CD4 101–200	Increased mortality when HAART deferred after 8 weeks if CD4 <100 Group  I versus Group II mortality = 27.7% versus 4.5% (𝑃=.03)	No difference between groups I and II regarding Grade 3 or 4 events, IRIS, or new OI
Velasco  et  al.  2009  [56]	- Mixed retrospective/ prospective study; - 313 patients; - 1996–2004	- Simultaneous: HAART within 2 mths of TB diagnosis; - Nonsimultaneous: HAART after 3 mths of TB diagnosis	- Decreased mortality in simultaneous group (9.3%) versus nonsimultaneous group (19.7%) (𝑃=.011); - No difference in virological/immunological outcomes	N/A
Torok  et  al.  2009 [57]	- Randomized, double blind, placebo-controlled trial; - 253 patients; - Vietnam; - Clinical diagnosis of TB meningitis	HAART started within 7 days (immediate arm) or at 2 mths (deferred arm) after initiation of TB treatment	Mortality: -Immediate arm: 76 deaths/127 pts; -Deferred arm: 70 deaths/126 pts (HR=1.16, 𝑃=.31)	Incidence of grade 3 or 4 adverse events first 2 mths: -Immediate: 86%; -Deferred: 75%  (𝑃=.04)
Abdool  Karim  et al.  2010 [58]	- Open-label, randomized, controlled trial; - 642 patients; - Durban, South Africa; - Only patients with positive sputum smear for acid-fast bacilli and CD4 count < 500/mm^3 included	HAART started either during TB treatment (in two integrated-therapy groups) or after completion of TB treatment (in one sequential-therapy group)	Mortality rate per 100 py: -Integrated arm: 5.4; -Sequential arm: 12.1 (𝑃=.003) Virological suppression 6 mths after HAART initiation: -Integrated arm: 91.1%; -Sequential arm: 86.7% (𝑃=.4)	Incidence of IRIS: -Integrated arm: 12.4%; -Sequential arm: 3.8%(𝑃≤.001); Grade 3 or 4 adverse events: Integrated arm: 30/100 py; Sequential arm: 32/100 py (𝑃=.69)
Blanc  et  al.  2010 [59]	- Open label randomized,; controlled trial; - 661 patients; - Cambodia; - Only patients with positive smear for acid-fast bacilli and CD4 count < 200/mm^3 included	HAART started at 2 weeks (early arm) or 8 weeks (late arm) after initiation of TB treatment	Mortality rate per 100 py: -Early arm: 8.28; -Late arm: 13.77 (𝑃=.002) Virological suppression 50 wks after HAART initiation: -Early arm: 95.6%; -Late arm: 95.6% (𝑃=.82)	Incidence of IRIS per 100 pm: -Early arm: 4.03; -Late arm: 1.44 (𝑃<.0001)

OI: Opportunistic infections IRIS: Immune reconstitution inflammatory syndrome EFV: Efavirenz NVP: Nevirapine pts: Patients HR: Hazard ratio py: Person-years pm: Person-months N/A: Not available.