Incidence of active tuberculosis among people living with HIV receiving long‐term antiretroviral therapy in high TB/HIV burden settings in Thailand: implication for tuberculosis preventive therapy

Abstract

Introduction Among high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand. Methods A retrospective study was conducted in 2018 using follow‐up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan–Meier method was used to estimate mortality after ART initiation. Results During a median of 5.1 years of ART (IQR 2.2–9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683–823) per 100,000 persons‐year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm 3 , adjusted sub‐distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47–2.92; 101–200 cells/mm 3 , aSHR: 2.21, 95% CI, 1.54–3.16; 201–350 cells/mm 3 , aSHR: 1.59, 95% CI, 1.11–2.28 vs. >350 cells/mm 3 ), male sex (aSHR: 1.40, 95% CI, 1.11–1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17–1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72–4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5–9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm 3 ) at the most recent visit. Conclusions In this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.

Prevalence, treatment outcomes and determinants of TB/HIV coinfection: A 4-year retrospective review of national tuberculosis registry in a country in a MENA region

“…The results of the present study revealed that patients diagnosed with TB/HIV coinfection were on average 9.54 years younger than other patients. This finding is consistent with the results of a study by Suwanpimolkul et al Moreover, the average age of HIV-positive patients when starting antiretroviral treatment in coinfection with TB was reported to be lower than other patients without coinfection [ 34 ], which may suggest that the presence of one disease accelerates the progression of another disease.…”

“…Patients diagnosed with TB/HIV coinfection had lower weight compared to other TB patients, which is in line with the findings of another study that investigated the occurrence of active tuberculosis among HIV-infected patients [ 34 ]. This may suggest that the presence of both TB and HIV exacerbates the progression of these diseases.…”

The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis

“…In the United Kingdom (UK), the incidence rate of tuberculosis among people receiving HIV care at UK Collaborative HIV Cohort sites was 1.3 per 1000 person-years [ 20 ] and 2.81 cases per 1000 patient-years in tuberculosis-low prevalence settings [ 21 ]. The tuberculosis incidence rate was 4.1 per 100 patient-year in Brazil [ 22 ] and 750 per 100,000 persons-years in Thailand [ 23 ]. In high or intermediate tuberculosis burden settings, the incidence rate of tuberculosis was 4.17 per 100 person-years, whereas in low-burden settings, it was 0.4 per 100 person-years [ 24 ].…”

Diagnosis and treatment of tuberculosis in adults with HIV

“…The addition of TB preventive therapy (TPT) to antiretroviral therapy has been shown to reduce TB incidence by 30% and mortality by 35% to 50%. [ 25 ] The recommended regimens for treating HIV complicated with latent TB include the administration of rifapentine and isoniazid once a week for 12 weeks, rifampicin daily for 4 months, or isoniazid and rifampicin daily for 3 months. Recommended alternatives are daily treatment with isoniazid for 6 or 9 months or daily treatment with rifapentine and isoniazid for 1 month.…”

“…[23] That is, a strategy of rapid antiretroviral therapy (ie, ART should be started within 7 days) should be implemented regardless of the CD4 + T-cell count. [24,25] Also, studies have shown that combination therapy with ART and anti-TB drugs is generally well tolerated. Early ART initiation allows for rapid immune recovery and reduces the risk of other opportunistic infections and all-cause mortality for people with HIV-TB co-infection.…”