The introduction of antiretroviral therapy (ART) has transformed HIV from a fatal illness into a manageable, chronic condition. As there is currently no cure for HIV, ART, typically including three antiretroviral drugs (ARVs), is a lifelong commitment, and there are concerns around long-term toxicities. Integrase strand transfer inhibitors (INSTIs) are one of the latest ARV classes to be approved and treatment guidelines uniformly recommend them as first-line treatment for people living with HIV (PLWH). However, limited data exist on long-term clinical outcomes associated with contemporary ART, including INSTIs, and contemporary ART regimens, including two-drug regimens. In this thesis, I use data from the International Cohort Consortium of Infectious Diseases (RESPOND) to assess the use and outcomes of contemporary ART, with a focus on two-drug regimens and INSTIs, including the association between INSTI use and incident cancer. I also assess temporal trends in cancer incidence across different ART-eras. RESPOND is a collaboration of 17 cohort studies, including approximately 30,000 PLWH from across Europe and Australia.
I found that uptake of dolutegravir compared to cobicistat-boosted elvitegravir or raltegravir has increased over time. INSTI discontinuation was low overall and mainly due to toxicity in the first 6 months of use. Discontinuation was higher for raltegravir, primarily due to treatment simplification, whilst discontinuation due to nervous system toxicities was highest on dolutegravir.
Virological and immunological outcomes were similar between those on two-drug and three-drug regimens. Additionally, after accounting for baseline characteristics, there was a similar incidence of severe clinical events on both regimen types.
When assessing cancer trends from 2006-2019, I found that whilst the age-standardised incidence of AIDS-related and infection-related cancers has decreased over time, body mass index-related cancers have increased, whilst non-AIDS-related cancers and smoking-related cancers remained constant. Overall, there was no association between cancer risk and INSTI exposure
