Recurrent Subclinical Tuberculosis Among Antiretroviral Therapy-Accessing Participants: Incidence, Clinical Course, and Outcomes

Abstract

Background: Undiagnosed asymptomatic subclinical tuberculosis (TB) remains a significant threat to global TB control, accounting for a substantial proportion of cases among people living with human immunodeficiency virus (HIV)/AIDS (PLWHA). We determined incidence, progression, and outcomes of subclinical TB in antiretroviral therapy (ART)-accessing PLWHA with known previous TB in South Africa.

Methods: A total of 402 adult PLWHA previously treated for TB were enrolled in the prospective Centre for the AIDS Programme of Research in South Africa TRuTH (TB Recurrence Upon TB and HIV treatment) Study. Participants were screened for TB with quarterly clinical and bacteriologic evaluation and biannual chest radiographs over 36 months. Those with suspected or confirmed TB were referred to the National TB Programme. Participants received HIV services, including ART. Incidence rate of TB was estimated using Poisson regression and descriptive statistical analyses summarized data.

Results: A total of 48 of 402 (11.9%) bacteriologically confirmed incident recurrent TB cases were identified, comprising 17 of 48 (35.4%) subclinical TB cases and 31 of 48 (64.5%) clinical TB cases. Age, sex, and body mass index were similar among subclinical, clinical, and no TB groups. Incidence rates (95% Confidence Interval [CI]) of recurrent TB overall, in clinical and subclinical TB groups were 2.3 (1.7-3.0), 1.5 (1.1-2.2), and 0.9 (0.5-1.4) per 100 person-years, respectively. In the subclinical TB group, 14 of 17 (82.4%) were diagnosed by TB culture only, 11 of 17 (64.7%) received TB treatment, and 6 of 17 (35.3%) resolved TB spontaneously.

Conclusions: High incidence rates of recurrent subclinical TB in PLWHA highlight inadequacies of symptom-based TB screening in high TB-HIV burden settings.

Keywords: HIV; clinical TB; incidence; prevalence; subclinical TB.

Figure 1.

Recurrent clinical and subclinical TB among people living with human immunodeficiency virus/AIDS on antiretroviral therapy previously successfully treated for TB. ^aAll treatment outcomes are defined per World Health Organization definitions and South African national TB treatment guidelines as follows: cure, a participant whose baseline smear or culture was positive at the start of treatment and is smear- or culture-negative in the last month of treatment and on at least 1 previous occasion 30 days prior; treatment completed, a participant whose baseline smear or culture was positive at the start of treatment and has completed treatment but does not have a negative smear or culture in the last month of treatment and on at least 1 previous occasion more than 30 days prior. The smear examination may not have been done or the results may not be available at the end of treatment. Abbreviation: TB, tuberculosis.

Figure 2.

CD4:CD8 ratio pre- and post-recurrent subclinical and clinical tuberculosis (TB) diagnosis. Abbreviation: CD, cluster of differentiation.

Figure 3.

Viral load pre- and post-recurrent subclinical and clinical tuberculosis (TB) diagnosis.