PMID- 22010915
OWN - NLM
STAT- MEDLINE
DCOM- 20111102
LR  - 20220409
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Print)
IS  - 0028-4793 (Linking)
VI  - 365
IP  - 16
DP  - 2011 Oct 20
TI  - Integration of antiretroviral therapy with tuberculosis treatment.
PG  - 1492-501
LID - 10.1056/NEJMoa1014181 [doi]
AB  - 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.).
FAU - Abdool Karim, Salim S
AU  - Abdool Karim SS
AD  - Centre for the AIDS Programme of Research in South Africa, Durban, South Africa. 
      caprisa@ukzn.ac.za
FAU - Naidoo, Kogieleum
AU  - Naidoo K
FAU - Grobler, Anneke
AU  - Grobler A
FAU - Padayatchi, Nesri
AU  - Padayatchi N
FAU - Baxter, Cheryl
AU  - Baxter C
FAU - Gray, Andrew L
AU  - Gray AL
FAU - Gengiah, Tanuja
AU  - Gengiah T
FAU - Gengiah, Santhanalakshmi
AU  - Gengiah S
FAU - Naidoo, Anushka
AU  - Naidoo A
FAU - Jithoo, Niraksha
AU  - Jithoo N
FAU - Nair, Gonasagrie
AU  - Nair G
FAU - El-Sadr, Wafaa M
AU  - El-Sadr WM
FAU - Friedland, Gerald
AU  - Friedland G
FAU - Abdool Karim, Quarraisha
AU  - Abdool Karim Q
LA  - eng
SI  - ClinicalTrials.gov/NCT00398996
GR  - U19 AI051794/AI/NIAID NIH HHS/United States
GR  - U19 AI051794-05S2/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Antitubercular Agents)
SB  - IM
CIN - N Engl J Med. 2011 Oct 20;365(16):1538-40. PMID: 22010921
CIN - N Engl J Med. 2012 Feb 2;366(5):474; author reply 475-6. PMID: 22296084
MH  - AIDS-Related Opportunistic Infections/*drug therapy
MH  - Adult
MH  - Anti-Retroviral Agents/*administration & dosage
MH  - Antitubercular Agents/*therapeutic use
MH  - CD4 Lymphocyte Count
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - HIV Infections/complications/*drug therapy/mortality
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Tuberculosis/complications/*drug therapy
MH  - Viral Load
PMC - PMC3233684
MID - NIHMS340285
COIS- Author disclosure: Dr. S. Abdool Karim reports being listed as a coinventor on 
      two patents (2000/3437 and PCT/IB02/04550) that are part of the development of 
      clade C HIV vaccines; and Mr. Gray, receiving lecture fees from AstraZeneca, 
      Aspen Pharmacare, and Fresenius Kabi. No other potential conflict of interest 
      relevant to this article was reported.
EDAT- 2011/10/21 06:00
MHDA- 2011/11/04 06:00
PMCR- 2012/10/20
CRDT- 2011/10/21 06:00
PHST- 2011/10/21 06:00 [entrez]
PHST- 2011/10/21 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2012/10/20 00:00 [pmc-release]
AID - 10.1056/NEJMoa1014181 [doi]
PST - ppublish
SO  - N Engl J Med. 2011 Oct 20;365(16):1492-501. doi: 10.1056/NEJMoa1014181.