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Integrase strand transfer inhibitor (INSTI) use and cancer incidence
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AIDS Cancer Rate Wanes With Longer Time Taking an Integrase Inhibitor
IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021
Mark Mascolini
Among antiretroviral-naive people entering a RESPOND study cohort, the new AIDS cancer rate (incidence) dropped with longer time after starting an integrase inhibitor (INSTI) regimen [1]. And among people who had already taken antiretroviral therapy (ART) when entering their RESPOND cohort, longer time taking an integrase inhibitor was not linked to a rising rate of new cancers.
Researchers from University College London and RESPOND collaborators from across the globe noted that aging of the HIV population raises concerns about climbing incidence of age-related comorbidities, such as non-AIDS-defining cancers. Because INSTIs are a relatively new antiretroviral class, research has yielded scant data on potential long-term outcomes—such as cancers—with these drugs.
To address this issue, the investigators tracked RESPOND participants from their baseline date (cohort enrollment or January 1, 2012, whichever came later) until their first cancer, final follow-up, or December 31, 2019. The analysis did not consider precancers, relapse of a primary cancer, or nonmelanoma skin cancers. RESPOND is an international multicohort collaboration of infectious disease study groups [2].
In analyzing the potential impact of INSTIs on cancer incidence, the researchers lagged INSTI use by 6 months to account for slow development of cancer and to avoid the statistical pitfall of confounding by indication (people at higher cancer risk or with early cancer symptoms may be preferentially prescribed INSTIs because of their great potency). Study statisticians used generalized estimating equations to weigh associations between cancer incidence and lagged cumulative INSTI exposure. They separately analyzed risk of non-AIDS-defining cancers and AIDS-defining cancers.
The analysis included 29,340 people with HIV and a median age of 44 years. While 74% of study participants were men, 45% were men who have sex with men (MSM), and 70% were white. Median baseline CD4 count stood at 524. Two thirds of the group (68%) were antiretroviral-experienced with a viral load below 200 copies at their baseline date. Median ART duration in experienced people stood at 7.7 years
When follow-up ended, 13,950 participants (48%) had taken one or more INSTIs for a median of 32 months. Through a median follow-up of 6.18 years, 1078 new cancers developed (243 AIDS cancers and 835 non-AIDS cancers) for an incidence of 6.7 cases per 1000 person-years. The most frequent new cancers were non-Hodgkin lymphoma in 10.5%, lung cancer in 10.4%, Kaposi sarcoma in 9.8%, and anal cancer in 9.6%. After statistical adjustment for age, sex, ethnicity, HIV risk group, CD4 count, certain comorbidities, and other potential confounders, incidence of any cancer (AIDS or non-AIDS) was similar in people who had taken an INSTI and in those who had not.
INSTI exposure was not significantly associated with age group, smoking status, or CD4 nadir (all P > 0.1). In people who entered the cohort with antiretroviral experience, cancer incidence was similar regardless of INSTI treatment length (less than 6 months, 6 to less than 12, 12 to less than 24, 24 to less than 36, and 36 months or more).
In people who entered their cohort with no antiretroviral experience, cancer incidence dropped as INSTI experience grew (P < 0.0001). This association reflected falling rates of AIDS-defining cancers. Compared with no INSTI exposure, adjusted incidence rate ratio (aIRR) for all AIDS-defining cancers waned with increasing INSTI experience: For less than 6 months of INSTIs, aIRR 0.86, 95% confidence interval [CI] 0.52 to 1.43); for 6 to less than 12 months, aIRR 0.31, 95% CI 0.13 to 0.77); for 12 to less than 24 months, aIRR 0.22, 95% CI 0.09 to 0.53); for 24 to less than 36 months, aIRR 0.56, 95% CI 0.28 to 1.15); for 36 months or more, aIRR 0.25, 95% CI 0.08 to 0.78 (global P = 0.0002).
The researchers cautioned that INSTI exposure in this analysis may have been too short to show an association with cancer risk because cancers can take years to develop. They proposed that the link between longer INSTI use and falling AIDS-defining cancer incidence in initially ART-naive people probably reflects INSTI regimen-based improvements in immune function.
References
1. Greenberg L, Ryom L, Neesgaard B, et al. Integrase strand transfer inhibitor (INSTI) use and cancer incidence. IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract PEB143.
2. RESPOND Study Group. https://www.chip.dk/Studies/RESPOND/Study-Group
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