Gary Murphy

Missed opportunities for diagnosing primary HIV infection

Objective: To investigate the extent to which primary HIV infection (PHI) presents to healthcare providers and the degree to which it is unrecognised. Methods: All individuals diagnosed with having recent HIV infection between 2003 and 2005 were identified (based on the following criteria: an evolving antibody response, negative HIV test within 18 months or a serological testing algorithm for recent HIV seroconversion). Symptoms of PHI and previous presentation to other healthcare providers were ascertained from HIV clinic notes and laboratory records (a single laboratory performing all of the HIV tests in the area). Results: Of the 108 subjects, 103 (95%) were male and 93 (86%) were men who had sex with men. A total of 76 of the 108 individuals (70%) reported symptoms of seroconversion. Of these, 40 (53%) presented to a healthcare provider during the symptomatic period. Of these, 21 (52%) were diagnosed with having PHI at first presentation. In the 19 patients (48%) in which a diagnosis of having PHI was not made at first presentation, 15 were seen in primary care, 3 in accident and emergency, and 1 in genitourinary medicine (GUM). Conclusions: The diagnosis of PHI is often missed. Individuals in high-risk groups need to be informed to access healthcare when they experience symptoms of seroconversion. Non-HIV/GUM healthcare providers (especially primary care) may benefit from training in case recognition to improve rates of diagnosis.

Recent trends in HIV and other STIs in the United Kingdom: data to the end of 2002

Sexual health in the United Kingdom has deteriorated in recent years with further increases in HIV and other sexually transmitted infections (STIs) reported in 2002. This paper describes results from the available surveillance data in the United Kingdom from the Health Protection Agency and its national collaborators. The data sources range from voluntary reports of HIV/AIDS from clinicians, CD4 cell count monitoring, a national census of individuals living with HIV, and the Unlinked Anonymous Programme, to statutory reports of STIs from genitourinary medicine (GUM) clinics and enhanced STI surveillance systems. In 2002, an estimated 49 500 adults aged over 15 years were living with HIV in the United Kingdom, of whom 31% were unaware of their infection. Diagnoses of new HIV infections have doubled from 1997 to 2002, mainly driven by heterosexuals who acquired their infection abroad. HIV transmission also continues within the United Kingdom, particularly among homo/bisexual men who, in 2002, accounted for 80% of all newly diagnosed HIV infections acquired in the United Kingdom. New diagnoses of syphilis have increased eightfold, and diagnoses of chlamydia and gonorrhoea have doubled from 1997 to 2002 overall; STI rates disproportionately affect homo/bisexual men and young people. Effective surveillance is essential in the provision of timely information on the changing epidemiology of HIV and other STIs; this information is necessary for the targeting of prevention efforts and through providing baseline information against which progress towards targets can be monitored.

Does the recent increase in HIV diagnoses among men who have sex with men in the UK reflect a rise in HIV incidence or increased uptake of HIV testing

Objectives: To determine whether the increase in HIV diagnoses since 1997 among men who have sex with men (MSM) in the UK reflects a rise in HIV incidence or an increase in HIV testing. Methods: Estimates of HIV incidence were derived using data from UK HIV surveillance systems (HIV diagnoses; CD4 surveillance; unlinked anonymous surveys) for 1997–2004. Data on HIV testing were provided by KC60 statutory returns, voluntary testing and unlinked anonymous surveys in sentinel genitourinary medicine (GUM) clinics. Results: HIV diagnoses among MSM in the UK rose by 54% between 1997 and 2004 (from 1382 to 2124), with variation by age and geographical location. The number of HIV diagnoses among MSM <35 years of age in London showed no increase, but in all other groups it increased. Throughout the UK, uptake of HIV testing increased significantly among MSM attending GUM clinics between 1997 and 2004, including “at-risk” MSM (p<0.001). Direct incidence estimates (serological testing algorithm for recent HIV seroconversion assay) provided no evidence of a statistically significant increase or decrease in HIV incidence. Indirect estimates suggested that there may have been a rise in HIV incidence, but these estimates were influenced by the increased uptake of HIV testing. Conclusions: The number of HIV diagnoses increased among MSM in the UK between 1997 and 2004, except among younger MSM in London, in whom there was no change. The increase in HIV diagnoses among MSM in the UK since 1997 seems to reflect an increase in HIV testing rather than a rise in HIV incidence.

Recent infection testing algorithm (RITA) applied to new HIV diagnoses in England, Wales and Northern Ireland, 2009 to 2011

In 2009, Public Health England (PHE) introduced the routine application of a recent infection testing algorithm (RITA) to new HIV diagnoses, where a positive RITA result indicates likely acquisition of infection in the previous six months. Laboratories submit serum specimens to PHE for testing using the HIV 1/2gO AxSYM assay modified for the determination of HIV antibody avidity. Results are classified according to avidity index and data on CD₄ count, antiretroviral treatment and the presence of an AIDS-defining illness. Between 2009 and 2011, 38.4% (6,966/18,134) of new HIV diagnoses in England, Wales and Northern Ireland were tested. Demographic characteristics of those tested were similar to all persons with diagnosed HIV. Overall, recent infection was 14.7% (1,022/6,966) and higher among men who have sex with men (MSM) (22.3%, 720/3,223) compared with heterosexual men and women (7.8%, 247/3,164). Higher proportions were among persons aged 15-24 years compared with those ≥50 years (MSM 31.2% (139/445) vs 13.6% (42/308); heterosexual men and women 17.3% (43/249) vs 6.2% (31/501)). Among heterosexual men and women, black Africans were least likely to have recent infection compared with whites (4.8%, 90/1,892 vs 13.3%, 97/728; adjusted odds ratio: 0.6; 95% CI: 0.4-0.9). Our results indicate evidence of ongoing HIV transmission during the study period, particularly among MSM.

Non-disclosure of HIV status in UK sexual health clinics—a pilot study to identify non-disclosure within a national unlinked anonymous seroprevalence survey

Objectives To identify if HIV-infected individuals attending genitourinary clinics in the UK are not disclosing their HIV status, and to examine the potential utility of drug detection as a method to indicate non-disclosure. Methods HIV-positive samples from the unlinked anonymous seroprevalence survey from one London centre in 2009 had viral load (VL) assays performed to identify samples with VL below the level of detection (50 copies/ml, VLBLD) or <1000 copies/ml. After data matching, known HIV positives were excluded and the remaining samples analysed for the presence of a panel of antiretroviral drugs. Results Of 130 HIV-positive samples with sufficient clinical information and not undergoing an HIV test, 18 were classified as remaining undiagnosed after the clinic visit. Thirteen (72%, 95% CI: 47% to 90%) had a VLBLD (n=11) or VL <1000 copies/ml (n=2). Eight had sufficient volume to undergo ARV testing, and all were positive for the presence of drug; all with therapeutic levels of clinically appropriate combinations. Conclusions Non-disclosure of HIV status occurs among individuals attending sexual health services in the UK. This study demonstrates the feasibility and utility of using both VL and ARV assays in serum samples. Furthermore, the close correlation of detection of ARV with VLBLD suggests drug detection would be a useful tool to monitor non-disclosure prospectively, thus enabling the use of stored serum samples in future studies. The extent to which these findings can be extrapolated to other settings, and the potential impact of non-disclosure on undiagnosed estimates warrants urgent prospective study.

Prevalence of markers for HIV, hepatitis B and hepatitis C infection in UK military recruits.

An unlinked anonymous survey was conducted to measure the prevalence of selected markers for HIV, hepatitis B and C infection in recruits to the UK Armed Forces to inform future screening and hepatitis B vaccination policies. During 2007, nearly 14 000 left-over samples taken from new recruits for blood typing were collected, unlinked from identifiers and anonymously tested for HIV, hepatitis C and current and past cleared hepatitis B infection. Overall, serological evidence of HIV and hepatitis C was found in 0·06% and 0·06% of recruits, respectively. Evidence of past cleared and current hepatitis B infection was found in 3·63% and 0·37% of recruits, respectively. Overall, prevalence rates were broadly consistent with UK population estimates of infection. However, HIV and hepatitis B prevalence was higher in recruits of African origin than in those from the UK (P<0·0001). Screening for these infections is an option that could be considered for those entering Services from high-prevalence countries.

HIV testing--the perspective from across the pond.

The first assay to screen blood donations for HIV was licensed in the USA in 1985. Since then there has been a dramatic increase in the types and numbers of assays available for HIV testing coupled with improvements in the sensitivity and specificity of these assays. However, with this increase in choice the algorithms for the initial diagnosis and confirmation of HIV infection have also increased in diversity and complexity and no uniform algorithm exists. Different regulatory regimes have meant that different assays and assay formats are available worldwide. In the UK we have been fortunate in having access to the so called 4th generation HIV antigen/antibody assays for 10 years. The first 4th generation assay in the US was licensed last year. The availability of this class of assays has led to the development of new algorithms for use in the US market and this paper describes how after many years of diversity the HIV algorithms between the UK and US are now converging.

The effect of sample handling on cross sectional HIV incidence testing results

Objective(s) To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays. Methods Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4°C, 25°C and 37°C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay). Results Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4°C or 25°C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37°C prior to testing. Conclusions Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4°C or 25°C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays.

Implications for HIV testing policy derived from combining data on voluntary confidential testing with viral sequences and serological analyses

Objectives: Laboratory, clinical and sequence-based data were combined to assess the differential uptake of voluntary confidential HIV testing (VCT) according to risk and explore the occurrence of HIV transmission from individuals with recently acquired HIV infection, before the diagnostic opportunity. Methods: Between 1999 and 2002, nearly 30 000 anonymous tests for previously undiagnosed HIV infection were conducted among men who have sex with men (MSM) attending 15 sentinel sexually transmitted infection (STI) clinics in England, Wales and Northern Ireland. Using a serological testing algorithm, undiagnosed HIV-infected men were categorised into those with recent and non-recent infection. VCT uptake was compared between HIV-negative, recently HIV-infected and non-recently HIV-infected men. A phylogenetic analysis of HIV pol sequences from 127 recently HIV-infected MSM was conducted to identify instances in which transmission may have occurred before the diagnostic opportunity. Results: HIV-negative MSM were more likely to receive VCT at clinic visits compared with undiagnosed HIV-infected MSM (56% (14 020/24 938) vs 31% (335/1072); p<0.001). Recently HIV-infected MSM were more likely to receive VCT compared with those with non-recent infections (42% (97/229) vs 28% (238/844); p<0.001). 22% (95/425) of undiagnosed HIV-infected MSM with STI received VCT. Phylogenetic analysis revealed at least seven transmissions may have been generated by recently HIV-infected MSM: a group that attended STI clinics soon after seroconversion. Conclusions: The integration of clinical, laboratory and sequence-based data reveals the need for specific targeting of the recently HIV exposed, and those with STI, for VCT. VCT promotion alone may be limited in its ability to prevent HIV transmission.

O14 Investigating the recent infection testing algorithm (RITA): predictors of recent HIV infection among GUM clinic attendees

Background Testing for recent infection with HIV has been part of routine national surveillance in the UK since 2009. These data can be used to estimate HIV seroincidence in populations. For these estimates to be accurate, HIV testing behaviour must be independent of HIV acquisition risk. This is unlikely to be true, as much testing may be motivated or clinically indicated. Aims To identify demographic and behavioural differences between individuals diagnosed with recent (<6 months) vs longstanding HIV infection, and to assess the possible level of bias introduced by motivated testing. Methods Recent Infection Testing Algorithm (RITA) results were linked to Genitourinary Medicine Clinic Activity Dataset attendance records (providing data on attendance and sexual health) for the year preceding the date of RITA test and/or HIV diagnosis. Univariate analyses were performed examining age, sexual orientation, GUM clinic attendances, and STI history, to identify predictors of being diagnosed at early stages of HIV infection. Results Preliminary analyses show that among 628 newly diagnosed HIV-positive individuals, 14% (85/628) were diagnosed with recent HIV infection. Being diagnosed with a recent HIV infection was positively associated with younger age, men who have sex with men and having been diagnosed with any bacterial STI in the year preceding the HIV diagnosis (see Abstract O14 table 1). Those visiting a sexual health clinic more than twice in the previous year were also more likely to be diagnosed at early stages of HIV infection. Abstract O14 Table 1 HIV infection according to patient demographics Variable % (n) recent HIV infection % (n) longstanding HIV infection Unadjusted RR of being diagnosed with recent infection (95% CI) Age (mean 35 years, SD 9.98, range 16–66 years) – – 0.98 (0.96 to 1.00) MSM (vs heterosexual)* 76.5 (65) 45.5 (180) 1.68 (1.43 to 1.97) Previous STI†  Chlamydia trachomatis 21.2 (18) 14.9 (81) 1.42 (0.90 to 2.24)  Syphilis 8.2 (7) 7 (38) 1.18 (0.54 to 2.55)  Gonorrhoea 16.5 (14) 10.5 (57) 1.57 (0.92 to 2.69)  Lymphogranuloma venereum (LGV) 1.2 (1) 0.9 (5) 1.28 (0.15 to 10.8)  Any STI‡ 37.6 (32) 24.5 (133) 1.54 (1.13 to 2.10) Visits in the year preceding date of HIV diagnosis/RITA test†  >2 visits 68 (34) 54.8 (188) 1.24 (1.00 to 1.54) * n=481. † Recorded in the same GUM clinic. ‡ Includes Chlamydia, syphilis, gonorrhoea, LGV. Conclusions Important behavioural and demographic differences exist between individuals diagnosed with recent vs established HIV infections. Such differences must be considered when deriving incidence estimates among key at-risk groups. Further work to examine these trends among all RITA results, in particular the relationship with HIV testing patterns, is ongoing.