The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

Soeters, Heidi M.; Napravnik, Sonia; Patel, Monita R.; Eron, Joseph J.; Rie, Annelies Van

doi:10.1097/01.aids.0000434936.57880.cd

Cited by 19 publications

(17 citation statements)

References 36 publications

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“…This is similar to the situation in adults 8 and reinforces WHO recommendations to initiate cART soon after TB treatment is tolerated. 4 In young children, our exploratory sensitivity analyses suggest that the combination of TB treatment and super-boosted LPV/r-based cART may increase the risk of rebound and diminish CD4% reconstitution.…”

Section: Discussionsupporting

confidence: 80%

“…In adults, receiving TB treatment at time of cART initiation does not impair virologic or immunologic response to cART, 8 though it may be associated with an increased risk of long-term mortality. 9 Results of limited pediatric research to date suggest that starting cART during TB treatment improves survival, 10-12 and that concomitant TB treatment and cART does not increase mortality.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Tuberculosis Treatment on Virologic and Immunologic Response to Combination Antiretroviral Therapy Among South African Children

Soeters¹,

Sawry²,

Moultrie³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Many HIV-infected children are diagnosed with tuberculosis (TB), but the effect of TB treatment on virologic and immunologic response to combination antiretroviral therapy (cART) is not well documented. Methods: Secondary analysis of a prospective cohort of cART-naïve HIV-infected South African children aged 0-8 years initiating cART to assess the effect of TB treatment at time of cART initiation on virologic suppression (HIV RNA <50 copies/mL), virologic rebound (HIV RNA >1000 copies/mL after suppression), and CD4 cell percentage (CD4%) increase during the first 24 months of cART. Results: Of 199 children (median age 2.1 years), 92 (46%) were receiving TB treatment at cART initiation. Children receiving and not receiving TB treatment at cART initiation had similar median baseline HIV RNA (5.4 vs. 5.6 copies/mL), median time to virologic suppression (6.2 months in each group, aHR 1.36, 95% CI 0.94-1.96) and rates of virologic rebound by 24 months (23% vs. 24%, aHR 1.53, 95% CI 0.71-3.30). Children on TB treatment had significantly lower median CD4% at baseline (15.3% vs. 18.8%, P<0.01) and during the first 12 months of cART, but experienced similar median increases in CD4% at 6 months (9.9% vs. 9.6%), 12 months (14.2% vs. 11.9%) and 24 months of cART (14.5% vs. 14.2%). Exploratory analyses suggest that children receiving lopinavir/ritonavir-based cART and TB treatment may have inferior virologic and immunologic response compared to children receiving efavirenz-based cART. Conclusions: Receiving TB treatment at time of cART initiation did not substantially affect virologic or immunologic responses to cART in young children.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

The Effect of Tuberculosis Treatment on Virologic and Immunologic Response to Combination Antiretroviral Therapy Among South African Children

Soeters¹,

Sawry²,

Moultrie³

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…A recent systematic review concluded that individuals receiving TB treatment at the time of ART initiation have similar CD4 þ cell count increases during ART [15]. Our findings provide further support for this and indicate that ART can effectively restore CD4 þ cell counts in individuals presenting with HIV-TB co-infection, despite the numerous challenges faced in the management of these cases [4].…”

Section: Discussionsupporting

confidence: 76%

“…Potential mechanisms for impaired CD4 þ responses in the presence of HIV-TB co-infection include the practical difficulties associated with concurrent therapy, as well as possible immunological mechanisms due to increased T-cell activation and apoptosis [14]. A recent systematic review suggested that CD4 þ cell reconstitution appeared similar in individuals receiving TB treatment at the time of ART initiation compared to those who did not have co-existent TB [15]. However, due to study heterogeneity, a meta-analysis was not possible; considerable debate therefore remains regarding the impact of TB on CD4 þ responses to ART.…”

Section: Introductionmentioning

confidence: 99%

CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection

Brown

Zenner

et al. 2015

Aids

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“…Reduced viral suppression in young children on tuberculosis co-treatment when on a ritonavir-boosted lopinavir-based regimen has been previously reported. 23-26 Although efavirenz is also metabolized by the same hepatic enzyme system, there does not appear to be a requirement to increase its dose, nor is there the need for any additional drug to boost its levels, thereby making this regimen option the more suitable alternative.…”

Section: Discussionmentioning

confidence: 99%

Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa

Coovadia

Abrams

Strehlau

et al. 2015

JAMA

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Importance Advantages of using efavirenz as part of treatment for HIV-infected children include once-daily dosing, simplification of co-treatment for tuberculosis, preserving ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission (PMTCT). Objective To evaluate whether nevirapine-exposed children, initially virally-suppressed on ritonavir-boosted lopinavir-based therapy, can transition to efavirenz-based therapy without risk of viral failure. Design, Setting, Participants Randomized, open-label, non-inferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, June 2010 to December 2013. Three hundred HIV-infected children exposed to nevirapine for PMTCT, ≥ 3 years of age, and with plasma HIV RNA <50 copies/ml on ritonavir-boosted lopinavir-based therapy were enrolled; 298 were randomized, and 292 (98%) were followed to 48 weeks post-randomization. Intervention Switch to efavirenz-based therapy (n=150) or continue on ritonavir-boosted lopinavir-based therapy (n=148). Main Outcomes and Measures Risk difference (delta) between groups in (1) viral rebound; i.e., one or more HIV RNA >50 copies/ml, and (2) viral failure; i.e., confirmed HIV RNA >1000 copies/ml; with a non-inferiority bound for the delta of −0.10. Immunologic and clinical responses were secondary endpoints. Results The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n=26) in the efavirenz group and 0.284 (n=42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n=4) in the efavirenz and 0.020 (n=3) in the ritonavir-boosted lopinavir group. The risk difference of viral rebound was 0.107 (1-sided 95% CI: 0.028,∞) and −0.007 (1-sided 95% CI: −0.036, ∞) for viral failure. We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (p<.001) for both endpoints. By 48 weeks, CD4 percentage was 2.88 (95% CI: 1.26, 4.49) units higher in the efavirenz than in the ritonavir-boosted lopinavir group. Conclusions and Relevance Among HIV-infected children exposed to nevirapine for PMTCT and initially virally-suppressed on ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these.

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The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

Cited by 19 publications

References 36 publications

The Effect of Tuberculosis Treatment on Virologic and Immunologic Response to Combination Antiretroviral Therapy Among South African Children

The Effect of Tuberculosis Treatment on Virologic and Immunologic Response to Combination Antiretroviral Therapy Among South African Children

CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection

Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa

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