Antiretroviral Therapy Outcomes in HIV-Infected Children after Adjusting Protease Inhibitor Dosing during Tuberculosis Treatment

Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6-24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB. Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons. Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation

Toxicity outcomes during 12 months after initiation of TB co-treatment by modification made to the PI-containing regimen.

a<p>Toxicity outcomes in children on superboosted LPV/r significantly different to children taking ritonavir only if ≥ grade 1 is selected as the cut-off.</p

Virologic, clinical and immunological outcomes at 6 and 12 months between children co-treated for TB stratified by the modifications made to their PI-based regimen and comparisons not co-treated for TB.

a<p>super-boosted LPV/r group significantly different from comparisons p<0.05,</p>b<p>double dose LPV/r group significantly different from comparisons p<0.05.</p>c<p>ritonavir group significantly different from Neverest comparisons.</p

Flow diagram of study participants.

<p>Flow diagram of study participants.</p

Characteristics of children who initiated TB treatment by modification made to antiretroviral treatment (ART) regimen.

*<p>Percents add up to >100% because more than one type of TB or diagnostic intervention was possible in the same child.</p>**<p>Other diagnostic evaluations include lymph node biopsy (2), gastric washing (1).</p>***<p>Other medications include prednisone (3), ciprobay (3), ethambutol (3).</p

Pre-antiretroviral treatment (ART) characteristics stratified by the modification made to the ART regimen among 294 children treated for TB and 232 comparison children not treated for TB at each site.

a<p>Denominators in each group are as shown.</p>b<p>superboosted LPV/r group significantly different from Shezi comparisons p<0.05.</p>c<p>double dose LPV/r group significantly different from Shezi comparisons p<0.05.</p>d<p>ritonavir group significantly different from Neverest comparisons p<0.05.</p