triple therapy in HIV infection

Last reviewed 01/2022

There is evidence that triple combination antiviral therapy is the most effective initial therapy for established HIV infection in adults and adolescents (1).

There are various choices of triple therapy (2):

• two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) - this regimen is recommended. The advantages of this regimen include that it is equivalent or superior in surrogate marker trials compared with protease inhibitor (PI) based regimens and has easier adherence. Disadvantages include that single mutations may lead to cross-class resistance and there is no randomised clinical trial (RCT) endpoint data
• two NRTIs and one PI - there is evidence of this regimen in late disease and RCT evidence with clinical endpoints. However unfortunately toxicity is common, drug interactions may occur and there is a high pill burden
• three NRTIs - this regimen should be considered for patients with low viral loads and adherence concerns. The advantages of this regimen include that it spares PI and NNRTI classes, there are fewer drug interactions, and there is a low pill burden. Disadvantages include there is no RCT endpoint data and the regimen may be less effective at high viral loads

'Many clinicians favour an NNRTI based regimen for initial therapy, reserving PIs for later use and three NRTIs for patients with potential drug interactions, a low viral load and perceived to have major adherence difficulties.' (2)

Various studies have reported the dramatic decreases in mortality among individuals infected with human immunodeficiency virus (HIV) since the widespread introduction of highly active antiretroviral therapy (HAART) in industrialized countries (3).

• in industrialized countries, persons infected sexually with HIV now appear to experience mortality rates similar to those of the general population in the first 5 years following infection, though a mortality excess remains as duration of HIV infection lengthens
• individuals exposed to HIV through intravenous drug use had a higher excess risk of death than persons infected sexually with HIV

A review has suggested (4) that people living with HIV can currently expect to live a normal life span if able to achieve durable viral suppression on combination antiretroviral therapy

• however this requires lifelong medication and will still suffer from higher rates of cardiovascular, renal, liver and neurologic disease

Reference:

1. Jordan R, Gold L, Cummins C, Hyde C. For increasing numbers of drugs in antiretroviral combination therapy. Systematic review and meta-analysis of evidence. BMJ 2002;324:757-760.
2. Pozniak A et al. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. BHIVA writing committee on behalf of the BHIVA executive committee. HIV Medicine 2001;2:276-313 http://www.bhiva.org/guidelines.htm
3. Bhaskaran K et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population.JAMA. 2008 Jul 2;300(1):51-9.
4. Passaes CP, Sáez-Cirión A.HIV cure research: advances and prospects. Virology. 2014 Apr;454-455:340-52