Integration of antiretroviral therapy with tuberculosis treatment.
BACKGROUND
We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.


METHODS
We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here.


RESULTS
At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006).


CONCLUSIONS
Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.).
Centre for the AIDS Programme of Research in South Africa, Durban, South Africa. caprisa@ukzn.ac.za
Salim S
SS
Abdool Karim
Kogieleum
K
Naidoo
Anneke
A
Grobler
Nesri
N
Padayatchi
Cheryl
C
Baxter
Andrew L
AL
Gray
Tanuja
T
Gengiah
Santhanalakshmi
S
Gengiah
Anushka
A
Naidoo
Niraksha
N
Jithoo
Gonasagrie
G
Nair
Wafaa M
WM
El-Sadr
Gerald
G
Friedland
Quarraisha
Q
Abdool Karim
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*; D019562:Viral Load
D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents