The impact of a combined TB/HIV intervention on the incidence of TB infection among adolescents and young adults in the HPTN 071 (PopART) trial communities in Zambia and South Africa

Abstract

Background: HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years.

Methods: A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up.

Results: We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063).

Conclusion: In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the population level dynamics of HIV and TB.

Fig 1. Enrolment and follow-up of the infection cohort.

Fig 2

Incidence rates of TB infection per 100 person-years (2a) and estimates of the Log Ratio Residuals (2b) comparing the arm A and arm C community in each of the seven triplets.

Fig 3. Adjusted rate ratio of incidence of TB-infection comparing arm A with arm C communities using alternative definitions of incident TB-infection incident (sensitivity analysis).

(1) Predefined analysis with incident case of TB-infection defined as a participant with a baseline QFT IFN-gamma response <0.2 IU/ml for both TB1Nil and TB2Nil tube and an IFN-gamma response of > = 0.7 IU/ml in either TB1Nil or TB2Nil in a subsequent blood sample at 12- or 24-month follow-up. (2) Same as (1) but using 1.05 IU/ml instead of 0.7 IU/ml. (3) Same as (1) but using 1.4 IU/ml instead of 0.7 IU/ml. (4) Same as (1) but only considering the TB1Nil IFN-gamma response. (5) Same as (1) but only considering the TB2Nil IFN-gamma response. (6) Same as (1) but using the mean of the IFN-gamma responses of TB1Nil and TB2Nil. (7) Analysis restricted to TB-incidence between 0 and 12 months using same definition of TB-incident case as in (1).

Fig 4. Rate ratio of incidence of TB-infection comparing arm A with arm C communities expanding the number of characteristics to adjust for at stage one of the two-stage cluster level analysis (sensitivity analysis).

(1) TB-infection defined as those with an IFN-gamma response of > 0.7 IU/ml at baseline among all with at least one follow up sample at 12- and/or 24 months. (2) Individual HIV-status at baseline as reported in Table 2. (3) Education as reported in Table 2.