The trial was published by The Lancet HIV journal and was carried out in fully public centres in Catalonia. The Hospital Clínic/IDIBAPS coordinated the trial, led by Dr. Senior Consultant and Associate Professor of Medicine at the Infectious Diseases Service of the Hospital Clínic de Barcelona and member of the group AIDS and HIV infection of IDIBAPS. The other participating centres were the Hospital Germans Trias i Pujol, the Hospital de Sant Pau, the Hospital de Bellvitge, the Hospital de Vall d’Hebron, and the Hospital Arnau de Vilanova de Lleida. This research has shown the efficacy of dual therapy for HIV treatment, with dolutegravir and lamivudine, compared with the standard treatment with three drugs -dolutegravir and tenofovir-emtricitabine-.
HIV is a disease that affects the cells of the immune system and prevents it from functioning normally. People infected with HIV require antiretroviral drugs that make the disease chronic but do not cure it. Over time, there is an accumulated risk of toxicity or interactions with other drugs prescribed for other diseases. Therefore, this trial’s research team considered dolutegravir to be a drug that did not present a risk of serious pharmacological interactions, was well tolerated, was a drug with a high barrier to the generation of resistance, and did not present any time or dietary restrictions.
Dolutegravir is a second-generation integrase inhibitor with high potency. Integrase is an enzyme found in HIV and allows the insertion of viral DNA into the DNA of our cells, more specifically the CD4 lymphocytes. Dolutegravir is a drug that prevents this insertion and thus our immune cells are not infected and can continue to perform their protective function. This drug, like other antiretrovirals, reduces the possibility of developing Acquired Immunodeficiency Syndrome (AIDS), other serious infections and cancer.
The 265 participants at the trial were adults aged 18 and over, with a positive HIV serological test and asymptomatic, who were receiving the standard triple therapy and were well controlled. Some of them were switched to monotherapy with dolutegravir, others to dual therapy with dolutegravir and lamivudine, and others continued with their triple therapy. Each participant in the trial was called to their hospital every 12 weeks during the 48-week trial period. They underwent a blood test to detect the level of HIV RNA in the blood plasma, the concentration of immune system cells such as CD4 and CD8, and other parameters were analysed such as glucose, creatinine, insulin, lipids and vitamin D.
Monotherapy with dolutegravir was found to be suboptimal, and therefore the study continued comparing dolutegravir plus lamuvidine with the standard triple therapy. After 48 weeks, a similar efficacy was observed in both treatment regimens. However, the dual therapy involved providing a lower quantity of drugs and thus entailed a lower risk of toxicity than the long-term triple therapies. So, switching from triple to dual therapy represented an improvement in the quality of life of HIV patients. Moreover, it was seen that the dual therapy with dolutegravir did not cause resistance, most of the side effects were mild or moderate, and there were no significant differences in side effects between the two groups.
The weight of the patients increased by 1.5 kg on average with the dual therapy compared with the triple, but no impact was observed between the change in weight and changes in metabolic parameters. No significant neuropsychiatric aspects such as sleep quality were seen to change in patients with dual therapy compared with those in the other group.
All the trials that aim to improve existing treatments, reducing side effects and toxicity, without increasing the cost, are promising, as shown in this trial carried out thanks to the Instituto de Salud Carlos III (Carlos III Health Institute), the Red de Investigación en Sida (AIDS Research Network) and ViiV Healthcare. The clinical trial for this research into the treatment of HIV is one of the most important to be carried out in Catalonia in terms of the number of participants. It is hoped that its conclusions will have a positive impact on the treatment of people living with HIV.
Authors: Dr. Elisa de Lazzari, Dr. José Luis Blanco, and Dr. Esteban Martínez. Hospital Clínic de Barcelona/IDIBAPS Infectious Diseases Service Research Group