Timing of Antiretroviral Therapy for HIV-1 Infection and Tuberculosis

Abstract

Background Antiretroviral therapy (ART) is indicated during tuberculosis (TB) treatment of patients infected with HIV-1, but the urgency to start ART at TB diagnosis for patients of varying levels of immune compromise is not known. Methods We conducted an open label, randomized study comparing immediate (within 2 weeks of TB treatment initiation) to early (8–12 weeks) ART among HIV-1 infected patients with CD4+ lymphocytes < 250/mm3 and suspected TB. The primary study endpoint was proportion of patients who survived without an AIDS-defining illness at 48 weeks. Results 809 patients with median baseline CD4+ lymphocytes of 77 cells/mm3 and HIV-1 RNA of 5.43 log10 copies/mL were enrolled. In the immediate arm, 12.9% of patients experienced an AIDS-defining illness or death by 48 weeks compared to 16.1% in the early arm (p=0.45; 95% confidence interval (CI) for difference: −1.8%, 8.1%). In patients with screening CD4+ lymphocytes <50 cells/mm3, 15.5% of patients on the immediate arm vs. 26.6% on early ART experienced an AIDS defining illness or death (p=0.02; difference CI: 1.5%, 20.5%). TB immune reconstitution inflammatory syndrome (IRIS) was more common with immediate ART (11% vs. 5%: p=0.002). Viral suppression at 48 weeks was 74% and did not differ between arms (p=0.38). Conclusion Overall, immediate ART did not reduce AIDS-defining illnesses and death compared to early ART. For persons with CD4+ lymphocytes < 50 cells/mm3, immediate ART had 42% less AIDS defining illnesses and death compared to early ART. (ClinicalTrial.gov number NCT00108862.)

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…506 Initiating antiretroviral therapy during tuberculosis treatment improves survival; 315,317 integrating tuberculosis and HIV care is costeffective; 507 early initiation of antiretroviral therapy in people with MDR tuberculosis and HIV substantially reduces mortality; 508 and, in patients with XDR tuberculosis and HIV, more deaths occur among those not receiving antiretroviral therapy. 509 Despite this overwhelming supportive evidence and guidelines for integration, implementation is scarce.…”

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…All HIV‐infected children diagnosed with TB should also be started on ART; however, the optimal timing of ART initiation depends on the degree of immunocompromise. Adult RCTs showed significant reduction in mortality and progression to AIDS with earlier ART in patients with CD4 counts < 50 cells/μl (Starting ART at 3 Points in TB (SAPIT) 162, Cambodian Early versus Late Introduction of Antiretrovirals (CAMELIA) 163 and Immediate Versus Deferred Start of Anti‐ HIV Therapy in HIV ‐Infected Adults Being Treated for Tuberculosis (STRIDE) 164). A retrospective study in South African children, most of whom were severely immunocompromised with median CD4 percentage < 12%, also showed that delay of ART for longer than 2 months was associated with increased mortality and worse virological response 165.…”

The 15th Bangkok International Symposium on HIV Medicine

“…New drug development aims to shorten the TB treatment course with drugs that are easier to take, less toxic, cheaper, have fewer interactions and are effective in drug resistance, such as gatifloxacin, moxifloxacin, rifapentine and delamanid, which are in Phase III trials [102]. New evidence concerning the optimization of the timing of initiation of ART in HIV and TB coinfection has been provided by several studies (Camelia, ACTG 5221 and SAPiT studies [5][6][7]) essentially advising earlier ART commencement with advanced disease (i.e., CD4 <50 cells/µl) despite the increased risk of immune reconstitution disease. Major hurdles that still need to be overcome are the management of multidrug-resistant TB and the broadening of ART regimens that can be safely and effectively used with anti-TB therapy.…”