PrEPped for COVID? The association between HIV-PrEP use and COVID-19 among men and gender diverse people who have sex with men: findings from three large online surveys in the United Kingdom

Background: Oral tenofovir and emtricitabine taken as pre-exposure prophylaxis (HIV-PrEP) is highly effective at reducing Human Immunodeficiency Virus (HIV) acquisition. Nucleotide analogues have also been shown to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) polymerase activity in vitro, raising the question as to whether tenofovir-based HIV-PrEP could be useful for the prevention and treatment of COVID-19. We sought to examine the association between HIV-PrEP use and self-reported COVID-19 testing outcomes and respiratory symptoms among men and gender diverse people who have sex with men in the UK. Methods: Participants completed online surveys deployed at three time points during the COVID-19 pandemic (Survey 1 (S1) 23/06/20 − 14/07/20; S2 23/11/20 − 12/12/20; S3 23/03/21 − 14/04/21), including men (cis/transgender), transwomen or gender-diverse people reporting sex with another man (cis/transgender) or non-binary person assigned male at birth. The outcome was self-reported COVID-19 testing and COVID-19 related respiratory symptoms including a new continuous cough, high temperature or loss of smell and/or taste during the most recent lookback period. All participants reporting taking HIV-PrEP in the past year were compared with those who did not. Analysis was performed using logistic regression, adjusting for sociodemographic and behavioural factors. Results: Among 4,544 participants living without HIV across three surveys (89.7% of all survey respondents), 21.4% (n = 970) reported recently using HIV-PrEP, 564 (12.4%) participants reported respiratory symptoms and 160 (3.5%) reported a positive COVID-19 test. There was a slight, non-statistically significant positive association between HIV-PrEP use and a COVID-19 positive test in the first survey-period (P1) (adjusted Odds Ratio (aOR) = 1.11, CI = 0.51–3.98). This positive association significantly increased across survey periods (P2: aOR = 4.26, CI = 1.21–14.97, P3: aOR = 9.02, CI = 2.69–30.31). There was a positive association between HIV-PrEP use and respiratory symptoms in the first survey-period (aOR = 1.45, CI = 1.03–2.03). However, this positive association reversed in survey-period 2 and 3 (P2: aOR = 0.62, CI = 0.40–0.95, P3: aOR = 0.45, CI = 0.28–0.72). Conclusions: We found no evidence that HIV-PrEP use protected against COVID-19 among participants. Conversely, we identified a positive association between HIV-PrEP use and COVID-19 which may reflect uncaptured behaviours that increase COVID-19 exposure amongst those using HIV-PrEP. The decline in respiratory symptoms in HIV-PrEP users over time might reflect some immune protection following exposures to respiratory viruses through more social mixing or a direct impact of HIV-PrEP on symptom severity.