Mark Bloch1, Craig Rodgers2
- Holdsworth House Medical Practice and East Sydney Doctors, Sydney NSW
- St Vincent’s Hospital, Sydney NSW
Last reviewed: March 2016
Next review due: December 2019
Initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) in the naïve patient centres around two main questions: When to start therapy and what to therapy to start. Data from recently published studies have provided evidence supporting starting therapy as soon after diagnosis as possible. The standard use of a three-drug regimen consisting of an anchor drug with a backbone of two nucleoside analogue drugs remains the recommendation for therapy. The addition of newer drugs, particularly from the integrase strand transfer inhibitor (INSTI) class, with beneficial efficacy and tolerability, has changed the choice of the anchor drug used to commence therapy. Because the key determinant of treatment success involves a commitment by the patient to ongoing treatment adherence, the critical decision to initiate ART is the patient’s readiness and willingness to commence treatment.
The current gold standard of triple combination antiretroviral therapy (cART, previously referred to as highly active antiretroviral therapy or HAART) has evolved in the context of signiﬁcant advances in the understanding of viral dynamics and HIV drug resistance. Early trials of monotherapy with zidovudine demonstrated limited clinical beneﬁt and virological and immunological failure, now known to be due in part to the development of drug resistance. Studies of dual nucleoside reverse transcriptase inhibitors or nucleoside analogues (NRTIs) published in 1996-1997 showed improved survival in asymptomatic individuals. Shortly after, the early studies of triple therapy with two NRTIs and a protease inhibitor (PI) demonstrated a reduction in morbidity and mortality in individuals with advanced HIV.
Due to the existence of a latently infected pool of long-living CD4 cells (established early in HIV infection), currently available ART is unable to achieve eradication of HIV infection. The current goals of therapy are:
- attaining maximal and durable suppression of HIV replication (as measured by a viral load below the limit of detection) with a well tolerated and simplified cART regimen
- restoring and preserving immune function
- reducing HIV-related morbidity
- reducing non-acquired immune deficiency syndrome (AIDS) comorbidities
- improving both quality of life and survival
- preventing HIV transmission.
As newer agents with simpler dosing schedules (including ﬁxed-dose combinations) and more favourable toxicity proﬁles have become available, there has been a shift in emphasis towards early recognition and minimisation of treatment-related toxicities and early intervention with strategies to improve adherence, in order to achieve a durable treatment response.
In addressing the questions faced by individuals living with HIV and their clinicians – when to start therapy and which regimen to choose – the discussion below outlines the current consensus approach in Australia which is based on a mix of available clinical trial data and expert opinion. The Australian commentary on the US Department of Health and Human Services (DHHS) antiretroviral guidelines are reviewed regularly in parallel with the review of the DHHS guidelines, and the most recent iteration may be found on the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) website.