The effect of tuberculosis treatment on virologic and immunologic response to combination antiretroviral therapy among South African children Heidi M.

The effect of tuberculosis treatment on virologic and immunologic response to combination antiretroviral therapy among South African childrenHeidi M. Soeters, Shobna Sawry, Harry Moultrie, Annelies Van Rie44th Union World Conference – Abstract OP-186-02November 2, 2013

Introduction

Introduction

In 2010, World Health Organization (WHO) guidelines recommended that HIV-infected infants and children start combination antiretroviral therapy (cART) as soon as TB treatment is tolerated1

Little is known about the effect of receiving TB treatment at time of cART initiation on response to cART in young children

1. WHO. Antiretroviral therapy for HIV infection in infants and children: towards universal access - 2010 revision. Geneva, 2010.

Introduction

The few studies that have assessed the effect of concomitant TB treatment on virologic or CD4 cell response to pediatric cART found that children receiving TB treatment at cART initiation may experience:

Lower rates of virologic suppression2-4

Similar CD4 cell reconstitution2,4-6

Similar proportion of severe immunodeficiency7

2. Frohoff C, et al. PLoS One 2011; 6:e17273.3. Zanoni BC, et al. AIDS 2011; 25:49-55.4. Reitz C, et al. JID 2010; 201:1121-31.

5. van Dijk JH, et al. PLoS One 2013; 8:e55111.

6. Zanoni BC, et al. PLoS One 2012; 7:e33611.7. Fatti G, et al. JAIDS 2011; 58:e60-7.

Study Aim

Evaluate the effect of receiving TB treatment at the time of cART initiation on short- and long-term virologic and immunologic response to cART among children aged 0-8 years

Research Methods

Research Methods

Secondary analysis of data from the TB HIV IRIS and Nutrition in Kids (THINK) cohort studyStudy population

cART-naive children aged 0-8 years presented at Harriet Shezi outpatient pediatric HIV clinic or the Paediatric Wards of Chris Hani Baragwanath Hospital in Soweto, South Africa eligible for cART

Enrolled September 2009 to March 2012Follow-up: 24 months or until August 2013

Research Methods

2 groups:children on TB treatment at the time of cART initiationchildren who are TB-free at the time of cART initiation

cART regimen prescribed according to age and weight>3 years and >10 kilograms: Efavirenz-based cART <3 years or <10 kilograms: LPV/r-based cART­ Super-boosted LPV/r if on TB treatment

Eligible for inclusion in this secondary analysis if have at least 1 follow-up HIV RNA and/or CD4%

LPV/r, lopinavir/ritonavir

Research Methods

Study outcomes:Virologic suppression: first documented HIV RNA <50 copies/mL after cART initiationVirologic rebound: among those that suppressed, first documented HIV RNA >1000 copies/mLMedian increase in CD4% from cART initiationMedian CD4%Proportion with severe immunodeficiency*

*Defined according to World Health Organization age-specific classifications: CD4% <25% in children <11 months, CD4% <20% in children 12-35 months, CD4% <15% in children 36-59 months, and CD4 cell count <200 cells/µL or CD4% <15% in children >5 years.5

Results

Results

246 children enrolled in the THINK study and initiated cART 199 children had ≥1 follow-up HIV RNA and/or CD4%

92 (46%) children were receiving TB treatment107 (54%) were not receiving TB treatment at cART initiation

Results: Baseline Characteristics

Results: Virologic SuppressionMedian time to HIV RNA <50 copies/mL

6.2 months in both groups

aHR 1.20 (0.69, 2.08)

aHR 1.36 (0.94, 1.96)

aHR 1.23 (0.82, 1.84)

Results: Virologic Rebound

aHR 1.53 (0.71, 3.30)

Results: CD4% Response

Children on TB treatment had lower CD4% in the first 12 months, after which they caught up to children who were not on TB treatmentThose receiving TB treatment had a similar median increase in CD4%

3 months (7.2% vs. 6.5%)6 months (9.9% vs. 9.6%)12 months (14.2% vs. 11.9%)24 months (14.5% vs. 14.2%), all P ≥0.06

Results: ImmunodeficiencyAt almost all time points, a higher proportion of children on TB treatment had severe age-specific immunodeficiency

cART Regimen Stratified Results

No significant effect of TB treatment among children on efavirenz-based cARTAmong children on LPV/r-based regimens, those on TB treatment tended to have:

Increased time to suppression (9.5 vs. 6.8 months) Increased virologic rebound (29% vs. 20%)Hazard of rebound (aHR 2.34, 95% CI 0.80, 6.83)Lower CD4% at 3, 6, 12 monthsHigher proportion of severe immunodeficiency at 6, 12, 24 months

Conclusions

Summary of Findings

Despite having more advanced disease at baseline, children receiving TB treatment at cART initiation did not have a substantially different response to cARTBoth groups had similar rates of virologic suppression, virologic rebound, and CD4% increaseChildren on TB treatment remained more vulnerable ­ lower CD4% and a higher prevalence of severe

immunodeficiency throughout the first 2 years of cART

Combination of TB treatment and super-boosted LPV/r-based cART may result in suboptimal response to cART in younger children

Acknowledgements

National Institutes of Health (NIH)Funding for this study was granted by the United States NIH Award 1 R01 HD058972-01

PEPFAR/WRHI for core infrastructure The USAID’s Wits RHI PEPFAR Project provided partial funding for staff, equipment and technical support at the Harriet Shezi Children's Clinic.

REDCap Study data were collected and managed using the REDCap electronic data capture system hosted at University of North Carolina – Chapel Hill [NIH grant 1UL1TR001111-01].

THINK study staffParticipants and caregiversJoe Eron, Sonia Napravnik, Alan Brookhart

Thank you!Questions?