PI-based ART in children with HIV and HIV/TB coinfection in South Africa

South African HIV guidelines recommend PI-based regimens for children <3 years old. Young children mostly receive lopinavir/ritonavir (LPV/r) but in some cases full-dose ritonavir (RTV) is used if a child is also being treated for TB.

Cordula Reitz and co-workers evaluated factors associated with virologic suppression among children receiving protease inhibitors in Johannesburg in the NEVEREST study.

NEVERST enrolled HIV-infected children who had been perinatally exposed to nevirapine (NVP). Children age >6 months to 24 months received LPV/r based ART and children less than 6 months old or receiving TB treatment (rifampicin/isoniziazid for 6 months + pyrazinamide for 2 months) received RTV-based ART. All children received d4T+3TC.

Viral suppression was defined as reducing viral load to <400 copies/mL. Kaplan Meier methods were used to calculate the probability of achieving viral suppression at 9 months or death.

This analysis included 254 children with a median age of 8.75 months (IQR 5.18-13.8), median CD4 percentage 18.95% (IQR 12.8-24.5) and 80.2% were WHO stage III or IV.

Of these, 138 (54.3%) children started ART with a LPV/r-based regimen and 116 (45.7%) a RTV-based regimen. 54 (46.6%) were <6 months old and 62 (54.3%) were receiving TB treatment (by 9 months an additional 37 [14.6%] children began TB treatment).

The investigators reported an overall mortality rate of 14%. Higher mortality was significantly associated with younger age <12 months vs >12 months [AHR 2.9, 95%CI 1.1-7.8], pre-treatment weight for age z-score (WAZ) <-4 vs >-2 [AHR 3.3; 95%CI 1.4-8.2] and higher pre treatment viral load >750,000 copies/mL vs <100,000 copies/mL [AHR 3.1; 95%CI 0.4-23.5.

The probability of viral suppression (<400 copies/mL) was 83.7% at 9 months after starting ART. Children receiving TB treatment were less likely to achieve viral suppression than children never treated for TB, 78.3% vs 94.1% respectively.

The overall probability of viral rebound at 4 months was 17.6%. Only TB treatment was associated with viral rebound; 8/15 (53.3%) children who started TB treatment after ART and achieved viral suppression had viral rebound compared to 12% without TB and 2.8% probability among those who started TB treatment before ART, p<0.0001 [AHR 5.2; 95% CI 2.1-12.9].

Although the researchers reported high rates of viral suppression among children <2 years they wrote; How best to treat HIV-infected children who require TB treatment remains an unsolved problem. There is an urgent need to further evaluate the pharmacokinetics and clinical outcomes in children co-treated for these two diseases so that evidence-based recommendations can be made.

Comment

Once again, we need more PK data in younger children and better PI formulations.

Reitz et al. Virologic Response to protease inhibitor-based ART among children younger than 2 Years of age co-treated for TB in South Africa. 16th CROI, February 2009, Montreal, Canada. Abstract 910.
http://www.retroconference.org/2009/Abstracts/34444.htm