Timing of antiretroviral therapy in Cambodian hospital after diagnosis of tuberculosis: impact of revised WHO guidelines (original) (raw)
Related papers
Timing of antiretroviral therapy initiation in tuberculosis patients with AIDS: a decision analysis
2007
Tuberculosis (TB) is the leading cause of mortality in people living with HIV infection (PLHIV), 1 with almost 1 in 4 deaths attributed to HIV-associated TB. 1 A crucial question in caring for patients who are co-infected has been the timing of initiation of antiretroviral therapy (ART) after commencing TB therapy. 2 This is particularly pertinent in South Africa, a country with a high HIV-associated disease burden. Many problems are associated with initiation of ART shortly after commencement of TB therapy, including drug interactions, overlapping toxicities, development of the immune reconstitution syndrome (IRIS), and poor adherence to therapy due to a high pill burden. 2,3 These complications must be balanced against the high mortality in PLHIV co-infected with TB and the need to reconstitute their immune systems. In South Africa, before 2010 the decision to initiate or delay ART was based on the CD4 count and World Health Organization (WHO) staging of patients who were co-infected, according to the National ART Guidelines (2004). 4 Only PLHIV with a CD4+ count of <50 cells/µl or WHO stage IV disease were commenced within 1 month of starting TB therapy. Several studies (the CAMELIA study in Cambodia (N=661), the STRIDE study in four continents (N=806) and the SAPiT study in South Africa (N=642)) showed that early initiation of ART decreased mortality for HIV-associated TB with CD4+ counts <50 cells/µl (CAMELIA and STRIDE: 2 weeks post TB therapy, SAPiT: <4 weeks post TB therapy). 5-7 The SAPiT study also showed that ART initiated during TB therapy decreased mortality in higher CD4+ count strata when compared with ART initiated after completion of TB therapy. 3 In all three studies TB IRIS was more common when ART was initiated early, but did not account for any deaths. 3,5,6 The CAMELIA and STRIDE studies reported no significant differences in adverse drug events between any groups. 5,6 However, in the SAPiT study, adverse drug reactions requiring drug switches were more common in patients who initiated ART within 2 weeks of commencing TB therapy across all CD4+ count strata. 7 In addition to late initiation of ART, the CAMELIA study found that a body mass index (BMI) ≤16, extrapulmonary TB (EPTB) plus pulmonary TB (PTB), nontuberculous mycobacterium, and multidrug-resistant (MDR) TB were independent risk factors for mortality. 5 In the SAPiT study, a low CD4+ count was an independent risk factor for mortality. 7 The South African National ART Guidelines were changed in 2010, and now recommend ART initiation as soon as TB therapy is tolerated, usually between 2 and 4 weeks, for all HIV-associated TB in PLHIV with a CD4+ count ≤350 cells/µl. 8 As the outcomes of the above studies are not consistent, it was hoped that this study would contribute to the understanding of when to Background. HIV-associated tuberculosis (TB) is common in South Africa. The optimal time for initiating antiretroviral therapy (ART) in co-infected patients is a clinical challenge. Aim. We aimed to compare clinical outcomes of patients with HIV-associated TB who commenced ART at different stages of TB therapy. Methods. A retrospective chart review was conducted of 458 patients who initiated ART at ≤28 days (immediate), 29-56 days (early) and ≥57 days (delayed) after commencing TB therapy, and clinical outcomes after 6 months of ART were compared. Results. There was a higher mortality in the immediate group, although this was not significant. Renal impairment (hazard ratio (HR) 2.5; 95% confidence interval (CI) 1.3-4.9; p=0.004) and inpatient ART initiation (HR 3.7; 95% CI 1.6-8.2; p=0.001) were risk factors for HIVassociated TB mortality. A baseline haemoglobin concentration ≥10 g/dl (HR 0.2; 95% CI 0.1-0.6; p=0.003), extrapulmonary as opposed to pulmonary TB (PTB) (HR 0.3; 95% CI 0.1-0.7; p=0.005) and extrapulmonary plus PTB as opposed to PTB (HR 0.3, 95% CI 0.1-0.6; p=0.002) were significantly associated with decreased mortality. Conclusion. The timing of initiation of ART after commencing TB therapy was not significantly associated with increased mortality or survival. Patients with more advanced disease were more likely to die. Early HIV testing and ART initiation is recommended to decrease mortality.
Timing of Antiretroviral Therapy Initiation in Tuberculosis Patients With AIDS
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2007
Tuberculosis (TB) is the leading cause of mortality in people living with HIV infection (PLHIV), 1 with almost 1 in 4 deaths attributed to HIV-associated TB. 1 A crucial question in caring for patients who are co-infected has been the timing of initiation of antiretroviral therapy (ART) after commencing TB therapy. 2 This is particularly pertinent in South Africa, a country with a high HIV-associated disease burden. Many problems are associated with initiation of ART shortly after commencement of TB therapy, including drug interactions, overlapping toxicities, development of the immune reconstitution syndrome (IRIS), and poor adherence to therapy due to a high pill burden. 2,3 These complications must be balanced against the high mortality in PLHIV co-infected with TB and the need to reconstitute their immune systems. In South Africa, before 2010 the decision to initiate or delay ART was based on the CD4 count and World Health Organization (WHO) staging of patients who were co-infected, according to the National ART Guidelines (2004). 4 Only PLHIV with a CD4+ count of <50 cells/µl or WHO stage IV disease were commenced within 1 month of starting TB therapy. Several studies (the CAMELIA study in Cambodia (N=661), the STRIDE study in four continents (N=806) and the SAPiT study in South Africa (N=642)) showed that early initiation of ART decreased mortality for HIV-associated TB with CD4+ counts <50 cells/µl (CAMELIA and STRIDE: 2 weeks post TB therapy, SAPiT: <4 weeks post TB therapy). 5-7 The SAPiT study also showed that ART initiated during TB therapy decreased mortality in higher CD4+ count strata when compared with ART initiated after completion of TB therapy. 3 In all three studies TB IRIS was more common when ART was initiated early, but did not account for any deaths. 3,5,6 The CAMELIA and STRIDE studies reported no significant differences in adverse drug events between any groups. 5,6 However, in the SAPiT study, adverse drug reactions requiring drug switches were more common in patients who initiated ART within 2 weeks of commencing TB therapy across all CD4+ count strata. 7 In addition to late initiation of ART, the CAMELIA study found that a body mass index (BMI) ≤16, extrapulmonary TB (EPTB) plus pulmonary TB (PTB), nontuberculous mycobacterium, and multidrug-resistant (MDR) TB were independent risk factors for mortality. 5 In the SAPiT study, a low CD4+ count was an independent risk factor for mortality. 7 The South African National ART Guidelines were changed in 2010, and now recommend ART initiation as soon as TB therapy is tolerated, usually between 2 and 4 weeks, for all HIV-associated TB in PLHIV with a CD4+ count ≤350 cells/µl. 8 As the outcomes of the above studies are not consistent, it was hoped that this study would contribute to the understanding of when to Background. HIV-associated tuberculosis (TB) is common in South Africa. The optimal time for initiating antiretroviral therapy (ART) in co-infected patients is a clinical challenge. Aim. We aimed to compare clinical outcomes of patients with HIV-associated TB who commenced ART at different stages of TB therapy. Methods. A retrospective chart review was conducted of 458 patients who initiated ART at ≤28 days (immediate), 29-56 days (early) and ≥57 days (delayed) after commencing TB therapy, and clinical outcomes after 6 months of ART were compared. Results. There was a higher mortality in the immediate group, although this was not significant. Renal impairment (hazard ratio (HR) 2.5; 95% confidence interval (CI) 1.3-4.9; p=0.004) and inpatient ART initiation (HR 3.7; 95% CI 1.6-8.2; p=0.001) were risk factors for HIVassociated TB mortality. A baseline haemoglobin concentration ≥10 g/dl (HR 0.2; 95% CI 0.1-0.6; p=0.003), extrapulmonary as opposed to pulmonary TB (PTB) (HR 0.3; 95% CI 0.1-0.7; p=0.005) and extrapulmonary plus PTB as opposed to PTB (HR 0.3, 95% CI 0.1-0.6; p=0.002) were significantly associated with decreased mortality. Conclusion. The timing of initiation of ART after commencing TB therapy was not significantly associated with increased mortality or survival. Patients with more advanced disease were more likely to die. Early HIV testing and ART initiation is recommended to decrease mortality.
BMC Infectious Diseases, 2012
Background: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. Methods: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Interpretation: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.
BackgroundIn absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB- IRIS outside the central nervous system remains unclear. However, this guideline change was not ba...
International Journal of HIV/AIDS Prevention, Education and Behavioural Science, 2019
Introduction: The use of antiretroviral therapy (ART) has dramatically decreased HIV-associated morbidity and mortality in high-and low-income countries with a corresponding reduction in tuberculosis (TB) incidence. Nevertheless, the risk of TB remains substantially higher in people living with HIV (PLHIV) compared to non-HIV infected individuals. In Cameroon, free ART was introduced in 2007 and our understanding of the possible role of ART in reducing HIV-associated TB remains limited. We assessed TB incidence, mortality and risk factors for TB and mortality among PLHIV treated at Buea Regional Hospital between 2008 and 2014. Materials and Methods: In a retrospective study we reviewed the records of 1,477 HIV patients on ART. The data was entered and analysed using SPSS version 21. Bivariate and Multivariate logistic regression analysis were used to determine the risk factors associated with TB and mortality occurrences at 5% significance level. Results: Of the 1477 patients' records that was reviewed, females (70.7%) constituted a greater proportion. Majority of the participants (60.5%) were between the ages 21-40 years (mean: 37.5 ± 11.5. SD). A total of 209 patients developed TB giving an overall TB incidence density rate 4.25/100PYR (95% CI: 2.47-6.46). There was an increasing trend in the incidence of TB over the years from 1.69 (95% CI: 0.72-1.98) in 2008 to 19.63 (95% CI: 7.36-21.20) in 2014. The overall mortality rate was 12.4% (183/1477) of which 38.8% (71/183) of them were on TB treatment or previously treated for TB. In a multivariate analysis, low CD4 cells level at ART initiation (AOR: 1.3, 95% CI: 1.11-.2.10), WHO HIV clinical stage 3 and 4 (AOR: 1.52, 95% CI: 1.01-2.22) were significantly associated with increase odds of TB occurrence. Conclusion: Even in the era of HAART, TB still remains a significant cause of mortality among PLHIV and therefore efforts should be scaled-up for early diagnosis and prompt treatment of TB.