Lopinavir/ritonavir monotherapy a possible second-line option for treatment experienced children

Lopinavir/ritonavir monotherapy is safe and largely effective when used as second-line antiretroviral therapy for HIV-positive children, according to a Thai study published in the online edition of AIDS.

The study involved 40 children who switched from a double boosted protease inhibitor regimen. A year after switching to lopinavir/ritonavir monotherapy almost three quarters of children were still taking this treatment and had an undetectable viral load.

“This is the first report of lopinavir/ritonavir monotherapy as maintenance therapy in HIV-infected children,” comment the investigators.

A number of studies have explored the safety and efficacy of simplifying HIV therapy for adults. Most of the research has involved patients who have discontinued traditional triple drug therapy and changed to lopinavir/ritonavir (Kaletra) monotherapy.  

In Thailand, recommended second-line HIV therapy for children who have resistance to NRTIs and NNRTIs is a double boosted protease inhibitor regimen. This treatment can involve taking a large number of pills, is costly and can cause side-effects and there is a risk of drug interactions.

Therefore, investigators wished to see if switching children who achieved an undetectable viral load with a double boosted protease inhibitor combination to lopinavir/ritonavir monotherapy was safe and effective. The children were switched back to a double boosted protease inhibitor combination if they had two consecutive viral load measurements above 500 copies/ml, or three consecutive viral loads between 50-499 copies/ml.

A total of 40 children were recruited to the study. Most (36) were taking lopinavir/ritonavir plus saquinavir, and the other four patients were being treated with lopinavir/ritonavir and indinavir. The children had been taking these regimens for a median of 3.6 years. Their average age was a little under twelve and 50% were boys.

At baseline, the CD4 cell percentage was 27%. Although all the children had an undetectable viral load during recruitment to the study, 10% were found to have a detectable viral load at their baseline visit.

There were no deaths and none of the children experienced disease progression during the 48 weeks of the study. Neither CD4 cell count nor CD4 cell percentage changed significantly.

At the end of the study 31 patients (73%) were still taking lopinavir/ritonavir monotherapy and had a viral load below 50 copies/ml.

Five children had a viral load “blip” (a transient increase in viral load to above 50 copies/ml). The median time between switching treatment and the blip was twelve weeks, and viral load ranged between 52-94 copies/ml. Pill counts showed that three of the children had poor adherence, and one had low blood levels of their medication. Nevertheless, at week 48 all five children had a viral load below 50 copies/ml at the end of the study and were still taking monotherapy.

A total of nine children (23%) resumed their double boosted protease inhibitor regimen. The median time to the failure of monotherapy was 24 weeks. At the end of the study, 44% of the patients who had resumed double boosted protease inhibitor therapy had an undetectable viral load and none had major resistance to a protease inhibitor.

HIV therapy has been associated with increases in lipids, so the patients’ cholesterol, triglycerides and glucose were closely monitored. The investigators were disappointed to see that switching to monotherapy did not have a significant effect on lipids. They comment, “apparently, lopinavir/ritonavir was mainly responsible for the negative impact on lipids in the lopinavir/ritonavir containing regimens.”

Statistical anaylsis showed that the only factor that was significantly associated with the virological failure of lopinavir/ritonavir monotherapy was a baseline viral load above 50 copies/ml (adjusted hazard ration, 5.9; 95% CI, 1.5-24.2; p = 0.01).

“At week 48 after simplified second-line treatment from double boosted protease inhibitor to lopinavir/ritonavir monotherapy, 72.5% of children were still virologically controlled with lopinavir/ritonavir monotherapy,” write the researchers, who believe their study “will be useful for future research on monoboosted protease inhibitor therapy in HIV-infected children.”

They conclude, “our data support further evaluation of long-term efficacy and safety of boosted protease inhibitor monotherapy as a treatment simplification strategy in children.”