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

Abstract

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.

Virological response and resistances over 12 months among HIV‐infected children less than two years receiving first‐line lopinavir/ritonavir‐based antiretroviral therapy in Cote d’Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort

“…Fourth, our results also show good immune recovery, with a 10% increase in CD4 percentage, from 20% at baseline to 30% in median at 6 months. This result is comparable to those of other cohorts of children receiving ART in Africa [ 23 , 33 , 34 ]. We did not find an association between VS and factors found in other studies such as age, gender, previous exposures to PMTCT or to maternal ART, baseline WHO stage, CD4 percentage, or baseline viral load [ 23 , 35 – 37 ].…”

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

“…Children who initiated ART while on TB treatment were almost 5 times more likely to develop major PI mutations than children without TB or who had completed TB treatment prior to ART initiation. Several studies have demonstrated worse virological outcomes in children who received TB co-treatment at the time of ART initiation, but this had not been linked to the presence of drug resistance [ 16 , 58 – 60 ]. TB co-treatment may predispose patients to drug resistance since the large pill burden may impair adherence and rifampicin-induced cytochrome P450 activity may cause sub-therapeutic levels of LPV [ 9 , 61 , 62 ].…”

Effect of tuberculosis–HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy

“…Although some studies which used a higher viral load cut-off (400 copes/ml) found that TB-ART co-treatment decreased frequency of viral suppression [27], we failed to find an association in sensitivity analyses using this higher cut-off. Both studies; however, have noted that the impact of TB co-treatment varies by ART regimen, with the limited impact of TB co-treatment on viral load suppression among CHIV receiving NNRTI-based regimens, in contrast to CHIV on PI-based regimens, which may have inferior virologic and immunologic responses with TB co-treatment [26,27]. In our study, CHIV receiving PI-ART had a lower frequency of viral suppression than those receiving NNRTI-based regimens in univariate but not in multivariate analyses and was associated with decreased CD4 þ recovery in multivariate analyses.…”

“…Growth trajectories between CHIV with and without TB-HIV co-treatment may differ because of the differential growth effects of TB disease and its resolution or because of side effects of TB medications. The few studies that have evaluated HIV-TB co-infected children had inconsistent findings [26,27] regarding the impact of co-treatment on viral suppression or immunologic responses in CHIV. A better understanding of viral suppression and the pattern of growth reconstitution during TB-HIV co-treatment can inform treatment approaches and nutritional monitoring and supplementation strategies.…”