Evaluation of the impact of human immunodeficiency virus pre-exposure prophylaxis on new human immunodeficiency virus diagnoses during the COVID-19 pandemic

Background

Pre-exposure prophylaxis (PrEP) is the pre-emptive use of antiretroviral medication by HIV negative people to prevent HIV infection. The IPERGAY study showed a relative risk reduction in HIV acquisition of 86% in participants taking event based dosing of oral tenofovir DF and emtricitabine compared to the placebo group. ¹ Similarly the PROUD study showed the same effect with a daily dosing strategy. ² In September 2015, the World Health Organisation recommended that PrEP be offered to all people at a substantial risk of acquiring HIV. ³ In August 2016, PrEP was licensed for use in Europe including Ireland. ⁴ PrEP has been available in Ireland on private prescription since December 2017. Ireland’s national PrEP programme launched in November 2019 with PrEP medication free to all those meeting defined clinical eligibility criteria. ⁵ These criteria include testing negative for HIV and one of the following: having sex with someone who is HIV positive who is not on treatment or has a detectable viral load, men who have sex with men or transindividual who has sex with men, using post-exposure prophylaxis (PEP) in the last year, sexually transmitted infection in the last year, anal sex without condoms with more than one partner in the last 6 months, or chemsex in the last 6 months. Other criteria for eligibility include heterosexual men or women who are deemed by a specialist STI doctor to be at high risk of contracting HIV. ⁶

The GUIDe clinic in St James’s Hospital Dublin established a comprehensive HIV prevention and PrEP service in November 2019 in line with the Health Service Executive (HSE) national rollout of free PrEP. Clinical nurse specialists and consultants deliver PrEP clinics throughout the week both face to face and virtually (by phone consultation). ⁵ The service is a combination STI/HIV prevention service in line with national standards. ⁵ This programme includes risk reduction interventions, vaccination and a full sexual health screen every 3 months

Presenting late with HIV infection increases the morbidity and mortality for the individual. Improved access to HIV testing and PrEP are part of a strategy of HIV combination prevention aimed at reducing the rates of HIV infections and reducing late presentations of HIV.

We assessed the impact of the first year of the national PrEP programme on new HIV diagnoses in the largest sexual health and HIV service in Ireland and assessed if PrEP had an impact on the rate of late presenters versus those diagnosed with recent HIV acquisition. We also reviewed STI rates within our PrEP cohort in the 3 months prior to starting PrEP. We reviewed this in the context of COVID-19 occurring alongside the first year of free PrEP rollout in Ireland.

Methods

We compared the number of new diagnoses of HIV between November 2018 and 2019, before the introduction of the national PrEP programme with the number of new HIV diagnoses between November 2019 and November 2020 using data available from clinics and the hospital electronic patient record (EPR). The number of HIV tests performed in men who have sex with men (MSM) was also obtained in order to assess the uptake of testing between the two years. We defined recent HIV acquisition as individuals with a previous HIV negative test done within 6 months before testing positive plus Recent Infection Testing Algorithm (RITA) positivity or p24 Antigen positivity if available. RITA assays are a combination of laboratory assays, and clinical information to determine recency of a HIV infection. ⁷

Late presentation of HIV is defined as a CD4 count of less than 350 and or an AIDS- defining illness at diagnosis. ⁶ We reviewed CD4 count at time of HIV diagnosis (<200, <350, >350, and >500), P24 antigen status, date of previous HIV test, and RITA. We used the EPR to gather information on STIs in the PrEP cohort. Statistical analysis was done using the Chi-square test and analysed using IBM SPSS Statistics v.24.0 (IBM Corp, Armonk, NY).

Results

The Health Protection Surveillance Centre (HPSC) reported in 2018 that the rate of HIV notification in Ireland was 11 per 100,000 population, with a rate of 6.4 per 100,000 ⁸ of new diagnoses that had not previously been diagnosed abroad. ⁸ The HPSC received 167 notifications of new HIV positive diagnoses in Ireland amongst MSM between November 2018 and November 2019 in Ireland (see Table 1). A total of 1660 HIV tests were carried out on MSM at the GUIDe clinic from November 2018 to November 2019. There were 95 new HIV positive diagnoses, of which 63 patients (63.3%) were MSM.

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Table 1.

New HIV diagnoses by category.

	Nov 2018–Nov 2019	Nov 2019–Nov 2020
Total new HIV diagnoses in MSM in Ireland	167	72
Number of HIV tests carried out on MSM in the GUIDe clinic	1660	2199
Total number of new HIV diagnoses in GUIDe	95	73
Number of new HIV diagnoses that acquisition was MSM	63	48

22 patients had acquired HIV recently according to our definition described above. 11/22 (50%) had a negative HIV test within the last 6 months 6 of whom had a positive RITA and 1 also had positive p24 antigen. 9/22 had a positive RITA assay (2 p24 positive) without a negative test in the last 6 months, 2/22 (9.1%) had a positive p24 antigen without a negative HIV test in the last 6 months or positive RITA. Please see Table 2 for a breakdown of the CD4 count at diagnosis.

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Table 2.

CD4 count at diagnosis.

Nov 2018–2019 (Pre-PreP)	(n = 63)	Nov 2019–2020 (Year 1 of PrEP rollout)	N = 48
CD4 >500	24	CD4 >500	14
CD4 350-499	16	CD4 350-499	13
CD4 200-349	11	CD4 200-349	9
CD4 <200	12	CD4 <200	12

Two of the new HIV diagnoses had previously been prescribed PrEP but had defaulted from care: one individual stopped using Event Based Dosing six months prior to HIV acquisition due to constipation and was diagnosed incidentally on admission to hospital with an unrelated issue, and the other individual had been taking daily PrEP but had run out four months prior to diagnosis, with diagnosis being made on re-engagement with services for repeat prescription. Two individuals had been prescribed post-exposure prophylaxis (PEP) but were HIV positive on baseline bloods. 24 individuals (38.1%) reported a seroconversion illness prior to positive HIV test. 20 (31.7%) of these presented within 1 year of their seroconversion illness. Three (4.8%) individuals presented during their seroconversion illness.

The HPSC received 72 notifications of new HIV positive diagnoses in Ireland amongst MSM between November 2019 and November 2020 (see Table 1). There were 2199 HIV tests performed on MSM from November 2019 to November 2020 in the GUIDe clinic. From November 2019 to 2020 there were 73 new HIV positive diagnoses of which 48 (65.7%) were MSM. 67% of new HIV diagnoses in MSM in Ireland were diagnosed in the GUIDe clinic between November 2019 and November 2020.

8/48 individuals had recent acquisition of HIV according to our definition. 6/8 had a negative HIV test in the last 6 months, 1 was p24 antigen positive. 2/8 had a positive RITA without a recent negative HIV test. Please see Table 2 for a breakdown of the CD4 count at diagnosis.

Three (4.1%) had previously been prescribed (41%) PrEP. Two had been taking EBD incorrectly and intermittently and had not taken with every potential exposure, one was diagnosed HIV positive at PrEP clinic and the other by GP. One had taken PrEP as PEP incorrectly after a potential exposure. Three were diagnosed HIV positive on starting PEP. Twelve patients (25%) identified a seroconversion illness, all of which presented within one year of their seroconversion illness and three (6.25%) presented during their seroconversion illness.

The positivity rate of new HIV infections in our MSM cohort between November 2018 and November 2019 and between November 2019 and 2020 was 3.8% and 2.9% respectively, which is a significant decline in new HIV diagnoses between these two years (p value 0.0003).

546 patients registered with the PrEP service between November 2019 to December 2020 of whom 541 were cisgender males (99.9%) (plus one cisgender female and four trans-women)

Of the 545 males and transwomen taking PrEP, 201 (36.8%) had previously taken PrEP prior to the national programme.

The mean age of people taking PrEP was 33 years (18–75 years) and an interquartile range of 10 years.

338 (62%) opted for daily dosing, 205 (37.6%) opted for EBD, 2 (0.4%) took ‘Tuesday Thursday Saturday Sunday, (TTSS) dosing. 106 PrEP users (19.4%) opted to change their PrEP dosing during the national COVID-19 lockdowns in 2020 with 67 (12.3%) changing from daily to EBD, 13 (2.4%) changed from EBD to daily, one switched from TTSS to daily and one switched from TTSS to EBD. Only 18 (3.3%) took a break during lockdown.

248 patients (45.5%) were diagnosed with one or more sexually transmitted infectiond at baseline/3 months prior to starting PrEP. 117 (21.5%) individuals were diagnosed with Chlamydia trachomatis at one or more sites, and 155 (28.4%) were diagnosed with Neisseria gonorrhoeae at one or more sites. No lymphogranuloma venereum (LGV) was detected. 61 patients (11.2%) had new syphilis infection and 107 (19.6%) had previously treated syphilis.

76.7% were immune to hepatitis B, 35 (6.4%) were hepatitis B core antibody positive and four patients (0.7%) were hepatitis B surface antigen positive. Three patients (0.6%) were hepatitis C antibody positive. One individual had acute hepatitis C (AHCV) six months prior to the rollout of free PrEP; he was buying PrEP online at the time. One person had AHCV two months prior to free PrEP rollout; he was also self sourcing PrEP.

Discussion

The rollout of free PrEP in Ireland has occurred alongside the ongoing COVID-19 global pandemic including during level 5 lockdown. Ireland’s COVID-19 emergency plan involved 5 tiers of restrictions with level 5 being the highest level, when all non-essential hospital appointments and elective surgeries were cancelled, non-essential retail and hospitality venues were closed, and people were advised to work from home where possible. Our PrEP clinics moved to a virtual platform to facilitate social distancing and remained open throughout the pandemic. ⁹ Clinics rapidly changed during lockdown to involve a phone consultation by the PrEP clinical nurse specialist followed by a rapid clinic appointment for STI screening and bloods. A six month prescription was given in case of further level 5 lockdowns; however, three-monthly appointments were continued where possible in line with current PrEP guidelines. Face to face consultations with a doctor were continued for vulnerable patients, those with significant co-morbidities (renal, HBV/HCV infection, osteoporosis) or those in which language barrier was an issue. Sexually transmitted infections were treated in emergency clinic appointments.

This data shows a decline in the absolute numbers and the proportion of people testing positive for HIV during the COVID-19 lockdowns, with a statistically significant reduction in new HIV diagnoses in MSM between the year prior to the rollout of free PrEP and the first year of free PrEP in the setting of increased MSM HIV testing. Introduction of free PrEP and continued PrEP services/HIV testing during the pandemic has likely played a role. Currently there is little in the literature about the global rates of new HIV infections during COVID-19.

The PrEP cohort has grown inspite of lockdown with only 18 patients taking a break from PrEP due to restrictions. 144 patients were virtually assessed for PrEP in June 2020 compared to 139 patients who were assessed in February 2020, representing a 3.6% increase.. The Dean Street clinic in London conducted a survey on changing sexual behaviours during COVID-19 restrictions amongst HIV negative MSM in August 2020. ¹⁰ They found that 76% had been sexually active with 76% of these reporting sex outside of their household. ¹⁰ This indicates ongoing need for PrEP services during lockdowns.

The high number of sexually transmitted infections within our cohort underlines the need for regular STI testing. Increased number of infections, particularly rectal infections, indicates ongoing high risk behaviour and concurrent infections increase the risk of HIV acquisition in MSM.

Due to the high demand and requirement for STI screening, the HSE and ‘Sexual Health 24’ (SH:24) launched a pilot in 2021 offering free chlamydia, gonorrhoea, hepatitis B, hepatitis C, syphilis and HIV home testing kits to try meet demand in a high risk population as part of a pilot project. ¹¹ This pilot project is available to anyone over the age of 17 in Counties Dublin, Cork and Kerry. 5011 test kits were ordered on its launch date on the 5^th of January 2021 with a 2^nd launch occurring on the 29^th of March 2021 due to the high demand. To date, 14521 tests have been ordered as of the 1^st of July 2021 with 2060 ordered by MSM and 364 ordered by men who have sex with men and women. The high numbers of orders reflect the need for the service. The aim of the pilot project is to increase patients access to STI testing while reducing waiting times for clinic appointments and move asymptomatic screening out of clinics and to an online platform. ¹¹

Conclusion

PrEP use is associated with an upscale in numbers of HIV tests performed and leads to a reduction of new HIV diagnoses. This suggests that even during COVID-19 restrictions, PrEP is effective in preventing HIV acquisition among our MSM cohort. It is too early to say if PrEP reduces late presentations of HIV based on our findings. Further research into sexual practices in Dublin during COVID-19 is needed to assess if this had an impact on the lower rates of HIV acquisition during this time period. Of note the HPSC received an overall reduction in the numbers of HIV notifications in Ireland, likely due to COVID-19. High STI rates among our patients align with that of the United Kingdom and indicate ongoing high risk behaviour, again indicating that PrEP is effective. PrEP awareness and access to PrEP needs to be increased in other high-risk groups.