amfAR, The Foundation for AIDS Research

Lopinavir/Ritonavir Should Not Be Used Alone as Second-Line Therapy in Adults

Lopinavir (LPV) is an anti-HIV drug in the protease inhibitor (PI) class. LPV boosted by low-dose ritonavir—referred to together as LPV/rtv—is the PI most commonly used in resource-limited settings to construct second-line regimens in patients who have failed first-line therapy that included nevirapine or efavirenz. In a second-line regimen, the World Health Organization recommends that LPV/rtv be given in combination with two other anti-HIV drugs from another class known as nucleoside reverse transcriptase inhibitors (NRTIs). However, as HIV resistance testing is not widely available in resource-limited settings, it is often not possible to confirm which drugs in the combination remain active. This raises concerns over the potential unnecessary costs and side effects of drugs in a therapy regimen that are not confirmed to be effective.

drugs photograph
Photo: Kevin Tachman 

In this context, researchers in Thailand compared the outcomes of using a standard second-line regimen consisting of LPV/rtv and two NRTIs to using LPV/rtv alone. One hundred ninety-five patients who had failed first-line therapy were enrolled in the study in nine HIV treatment centers across Thailand. Half were randomly assigned to receive treatment with LPV/rtv alone, and the other half received LPV/rtv in combination with the NRTIs tenofovir and lamivudine. Resistance testing done for the purpose of this study showed that almost all patients had resistance to lamivudine and around 25 percent had resistance to tenofovir at the time of starting second-line therapy.

The study showed that after one year of treatment, fewer patients taking LPV/rtv alone had achieved full control of their HIV infections. Sixty-one percent had a viral load of less than 50 copies of virus/mL compared to 83 percent of patients taking the three-drug regimen. The difference was even larger in patients who had a very high HIV viral load of more than 100,000 copies of virus/mL when they started their second-line regimen. The patients who took LPV/rtv alone were 12 times less likely to fully control their HIV infection than those on the three-drug regimen.

These findings provide evidence that LPV/rtv alone is less effective than a standard three-drug second-line regimen in adults, even in patients with resistance to tenofovir and lamivudine, and should not be recommended.


Reference: Bunupuradah T, Chetchotisakd P, Ananworanich J, Munsakul W, Jirajariyavej S, Kantipong P, Prasithsirikul W, Sungkanuparph S, Bowonwatanuwong C, Klinbuayaem V, Kerr SJ, Sophonphan J, Bhakeecheep S, Hirschel B, Ruxrungtham K; the HIV STAR Study Group. A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: the HIV STAR study. Antiviral Therapy 2012. Oct 25. doi: 10.3851/IMP2452. [Epub ahead of print]