Abstract
HIV-1 transmitted drug resistance (TDR) is associated with transmission in men who have sex with men (MSM), non MSM clusters, sexually transmitted infections (STIs) and can lead to antiretroviral failure. UK guidelines recommend performing TDR testing in all newly-diagnosed people living with HIV. We audited performance of TDR in our large tertiary HIV department from 2014–2020. All new patients had TDR testing attempted in the study period. The rate of TDR was 8% and was associated with increasing age and having non-B subtype. Having non-B subtype was not associated with being non-UK born. Thirty-four percent of people were diagnosed with a bacterial STI at the time of HIV diagnosis, but STI diagnosis was not associated with TDR. There was no significant change in TDR over the 6-year audit period. TDR remains a small but significant problem. Identifying these populations and providing effective HIV prevention interventions will reduce HIV incidence and TDR.
Background
HIV-1 transmitted drug resistance (TDR) has been shown to be associated with HIV transmission among men who have sex with men (MSM), HIV transmission within non-MSM clusters, and sexually transmitted infections (STIs). 1 TDR is an important contributor to antiretroviral failure; the most recent published report suggests the prevalence of TDR in the UK is 7.5%. 2 The most frequent TDR mutations are seen for nucleoside reverse transcriptase inhibitors (NRTIs; 3.5%), non-nucleoside reverse transcriptase inhibitors (nNRTIs; 3.3%) and protease inhibitors (PIs; 1.7%). 2 Several genetically defined HIV-1 subtypes circulate: subtype B is most prevalent in the US, Europe, and Australia, subtype C is most prevalent in Africa, and CRF01_AE in Asia. 3 Between 2005-2013, non-B subtype accounted for 51.1% of HIV in the UK. 2 UK guidelines advise genotypic drug resistance testing of all new diagnoses. 4
Methods
We audited all new HIV diagnoses between January 2014 to March 2020 for genotypic resistance testing in our tertiary HIV centre which manages around 2500 people living with HIV (PLHIV). We reviewed demographic data to identify associations with TDR alongside prevalence, according to the WHO 2009 list of mutations for the surveillance of TDR. 5
Results
There were 218 new diagnoses of which 217 had a resistance test sent (1 stored due to COVID-19). Two hundred and twelve out of 217 had an available genotype (5 failed to amplify). Only 5 patients (1 in 2020 and 4 in 2019) had integrase inhibitor resistance testing requested. One hundred and ninety-one (90%) were MSM, 12/211 (6%) cis-female, 80/212 (38%) non-UK born and the median age was 36 years (IQR = 29–46). The overall prevalence of TDR was 17/212 (8.0%; 95%CI = 5.0–12.4); seven (3%) had an NRTI mutation, six (3%) had at least one nNRTI mutation and 4 (2%) had a PI mutation. There were no dual/triple class/integrase inhibitor mutations. There was no significant change in the prevalence of TDR over the study period (p = 0.6) (Table 1). Patients with TDR were older [median age 45 years (IQR 35–54, range 28–60) vs. median age 36 years (IQR 29–45, range 19–65), p = 0.006] and had non-B subtype (OR = 2.96, 95% CI = 1.08 to 8.13, p = 0.03). Although overall rates of bacterial STIs at diagnosis were high (34%), having a bacterial STI was not associated with TDR (OR 1.77, 95% CI = 0.66–4.82, p = 0.26) (Table 2). The overall prevalence of non-B subtype was 53/212 (25%, 95%CI = 19.6–31.2), and was not seen more frequently in non-UK-born individuals (OR = 1.24, 95% CI = 0.66–2.33,p = 0.51).
Transmitted drug resistance between 2014 and 2020 (N = 212).
Associations with transmitted drug resistance (TDR) (N = 212).
Discussion
TDR testing was attempted in all patients diagnosed and then managed at our centre. The prevalence of TDR is similar to the rest of the UK, does not appear to be decreasing over time, appears to be associated with increasing age and having non-B subtype, although the numbers in our study are small. We have also shown that the proportion of non-B subtype is less than reported in the rest of the UK; however, having non-B subtype was not associated with being non-UK born. Brighton has experienced a large sub-epidemic of HIV transmission mainly in UK-born MSM, possibly explaining the lower proportion of non-B subtypes found in this study. TDR remains a small but significant problem particularly in older MSM who may not access effective prevention strategies such as HIV testing, HIV pre-exposure prophylaxis and HIV partner notification. Although we were unable to ascertain any detail of HIV transmission in MSM with TDR in this audit, we hypothesise that these MSM may be acquiring their HIV from sexual networks with poor access to care, or originating outside the UK; however, more detailed work is required to show this. There are data from the UK showing TDR may originate from treatment-naïve MSM with similar genotypes to this study, in particular at nucleoside T215 i.e. mutations driven by older antiretroviral therapy; suggesting that transmission is not from individuals poorly adherent to treatment. 6 , 7 This may also explain why rates of new diagnoses and TDR have not significantly changed over the past 6 years. These data suggest that we need to continue efforts to increase testing for HIV amongst low-testing populations of MSM and provide opportunities for these MSM to access effective HIV prevention strategies.
There were several limitations of this audit including it being a small, single-centre study and our inability to control for variables associated with TDR and perform logistic regression due to the small numbers of MSM with TDR. It is important that we continue to monitor TDR in newly diagnosed PLHIV and establish robust mechanisms for future prevention of both HIV transmission and associated TDR.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
