The public health applications of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom

^a Public Health Laboratory Service, UK.
^b Institute of Child Health, University of London, 30 Guilford Street, London WC1N 1EH, UK.
^c Scottish Centre for Infection and Environmental Health, Clifton House, Clifton Place, Glasgow G3 7LN, Scotland.

Reprint requests to: Dr A Nicoll, HIV and STD Division, Communicable Disease Surveillance Centre, 61, Colindale Avenue, London NW9 5EQ, UK. E-mail: anicoll{at}phls.co.uk

Abstract

Background In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990.

Methods The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested.

Results The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C).

Conclusions Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.

Keywords HIV, serosurveillance, public health, surveillance

Accepted 23 August 1999

Rationale and History

When it was realised in the mid-1980s that infection with human immunodeficiency virus (HIV) was spreading globally the need to monitor transmission became a high priority. Surveillance for HIV infection and disease must overcome unique difficulties (Table 1). For example HIV's propensity, like other sexually transmitted infections, to spread at variable and unpredictable rates in different population sub-groups. Serosurveillance became possible once tests for antibodies to HIV-1 and HIV-2 (anti-HIV) became available in 1984–1985. Not all those at risk of HIV infection accept testing however, so that reports based on diagnostic testing^d may be unrepresentative and usually over or under-estimate prevalence. ^1–4 Equally, data from mandatory testing of blood donors, although useful, underestimates population prevalence because of exclusions of those at risk of infection.⁵

View larger version (38K): [in this window] [in a new window]   Figure 1 Schematic methodology of unlinked testing

Description of the UK programmes

The principles underlying the UK programmes were established prior to starting and have remained unchanged.^7,11,13 However the programmes' aims have developed as the potential of the data has been more fully realised (Table 2).¹³ The programmes consist of a series of multi-centre surveys mostly using specimens gathered routinely for screening purposes from groups who are predominately well and without obvious disease (Table 3). Groups at higher behavioural risk, such as attenders at sexually transmitted disease (STD) clinics (homosexual and bisexual males, injecting drug users (IDU) and heterosexual males and females) and IDU attending specialist services, are targeted, as are some groups at lower or general risk, such as childbearing women and women having terminations of pregnancy (Table 3). The surveys are broadly spread across the country but especially focus on London where prevalence is highest and changes have appeared first. In 1998 there were 242 participating centres and districts, 69 in London, 28 in Scotland and 145 elsewhere (Figure 2, Table 3). An important criterion in choosing survey designs was that the populations included would be relatively stable over time to allow prevalence monitoring. All surveys have run continuously since 1990/ 91. Additional limited duration surveys for HIV have included specimens from selected patients having blood counts tested in hospital laboratories, people in prison (prisoners) and for hepatitis C in a variety of specimens.^13,23

View larger version (48K): [in this window] [in a new window]   Figure 2 Surveys and source populations and geographical distribution of centres in the UK programme

The surveys were made possible through developments in laboratory techniques (Table 4) such as inexpensive serological tests and serum pooling, oral fluid antibody tests, and confirmatory algorithms that minimize use of expensive western blotting.^26–30 Laboratory costs per specimen tested are much lower than for diagnostic testing. The combined cost of all national HIV surveillance, of which these programmes are part, is considerably less than one per cent of the national HIV care and prevention budget.³¹

Public health applications

Unlinked anonymous surveillance provides minimally biased estimates of the prevalence of HIV infection in the groups sampled and the results are used to monitor infection in populations at higher and lower risk. Information is provided nationally and regionally, thus overcoming uncertainty in the interpretation of results from single clinics or small areas.

The surveys have had multiple applications (Table 5). They have rapidly detected new problems in defined geographical areas and population sub-groups, and the emergence of HIV in new areas. Although such changes have not always reflected increases in local transmission, they have warned of future increase in disease and increased risk of transmission.^37,38 The surveys of pregnant women have detected a sixfold rise in prevalence in London (Figure 3), and the emergence in 1991/92 of HIV in areas in Scotland beyond the initial epicentres of Edinburgh and Dundee.^23,39–41 In 1996–97 rises were detected for the first time in England outside London from below to above 0.15%.¹³ Further analyses indicated that infections in London were mostly among black African women.^41–44 As voluntary confidential testing of pregnant women in the UK has never detected more than 30% of prevalent infections and laboratories do not distinguish blood samples taken in pregnancy,²⁵ these changes would not otherwise have been detected in any timely way.^41,44

View larger version (14K): [in this window] [in a new window]   Figure 3 HIV prevalence trends in pregnant women in the UK

In the mid-1990s the surveys of injecting drug users (IDU) found that 15–20% of participants reported recent sharing of injecting equipment across the country, and that sharing was commoner among younger and female injectors.⁴⁷ Harm reduction efforts were modified in response to these findings.⁴⁸ In 1998 a widespread rise in sharing of over 10% was detected.²³ Equally the detection of heterosexual men and women dually infected with undiagnosed HIV and other acute STI from 1995 onwards revealed a previously unrecognised potential for heterosexual HIV transmission in London.¹³

Refocusing of HIV prevention programmes

The findings of the surveys have contributed to the UK's public health response to HIV and AIDS, which in the 1980s was rapid and aimed at the whole population.⁴⁹ With hindsight it was criticised as being unfocused.⁵⁰ In the UK, reported HIV infections and AIDS have been concentrated in London, with a secondary focus in Eastern Scotland.^12,51 However, these report data are always vulnerable to people not seeking testing. Unlinked anonymous survey data have helped re-focus preventive efforts by providing regular, timely, and accurate information indicating the groups and places most affected by HIV transmission. Analyses in the early 1990s, including data from the unlinked anonymous programme, indicated that the bulk of HIV transmission was taking place through male homosexual intercourse.⁵² Equally since heterosexual HIV prevalences among STD clinic attenders born in the UK and pregnant women outside London, Edinburgh and Dundee were very low (<0.5%), the programme demonstrated that heterosexual transmission elsewhere was rare, providing the best reassurance that there has as yet been no substantial indigenous heterosexual transmission.^13,39,53 This led, in 1995, to a national refocusing of HIV health promotion towards homosexual and bisexual men, reducing the earlier emphasis on heterosexual men and women⁴⁸ and allowing sexual health service providers outside London to prioritize other infections,⁵⁴ while being confident that should HIV infection levels rise, such a change will be recognised rapidly. Hence the programmes have produced useful negative data. Different programme data also ensured that IDU remained a priority group for prevention efforts. Although they showed low levels of HIV infection (<0.5%) among new IDU, they found prevalences of prior HBV infection of up to 10%, and increasing sharing of injecting equipment in all areas.^23,53,55

Measurement of HIV prevalence and incidence

The direct method of estimating prevalent infections⁵⁶ employs HIV prevalences from individual unlinked surveys applied to estimates of the size of source populations, (Figure 1) using data from a national survey of sexual behaviours;⁵⁷ each major component of the populations at risk is accounted for separately and adjustments made for overlapping risk groups and differential fertility among HIV infected and uninfected women.^56,58–60 Numbers of undiagnosed infections are combined with data from an annual survey of prevalent diagnosed HIV infections to obtain the numbers infected in each major risk group.⁵⁸ This has provided estimates of prevalent HIV infections similar to those made using indirect methods.⁶¹ Estimates of prevalent infections at different points in time have been combined with numbers of deaths among those infected with HIV to estimate numbers of new infections added to the population (approximately 1400 per annum) a proxy for HIV incidence.⁶¹

Behaviour monitoring and evaluating the effectiveness of behavioural and HIV testing initiatives

The unlinked anonymous surveys monitor key risk behaviours in national samples of the populations at highest risk. Acute STI among those known to be HIV infected provide the only routine measure of compliance with safe sex messages by HIV infected homosexual and bisexual men.²⁴ Progress towards a national target to reduce the sharing of injecting equipment is monitored through the survey of drug injectors.^53,62 Early diagnosis of HIV infection allows patients to benefit from risk reduction counselling, clinical monitoring, chemoprophylaxis and chemotherapy. The programme's surveys provide information on the proportions of infections that have not been diagnosed prevalent in a range of clinical settings, while additional analysis using reports of diagnosed infections provides estimates of underdiagnosis at a population level.^23,58,63 In 1997/98 about one-third of HIV infected homosexual and bisexual men attending STD clinics and over half of heterosexuals remained undiagnosed (Figure 4).⁶⁴ Analysis by country of birth has shown that African men are a particular group in which there are many undiagnosed HIV infections.^36,44 With other data⁶⁴ this has led to better targeting of diagnostic and other services to this group.¹³

View larger version (26K): [in this window] [in a new window]   Figure 4 Proportions of HIV infections diagnosed—survey groups 1997–1998

Improving projections of AIDS cases and other severe HIV disease

Since 1994 estimates of recent HIV infection and projections of cases of AIDS and severe HIV disease in England and Wales (needed for national budgeting) have used data from the unlinked programmes. Prevalence ranges derived using the direct method are used to constrain calculation projections of HIV and AIDS incidence, reduce the planning projections and thus narrow confidence intervals (Figure 5). An advantage of this approach is that, unlike the indirect methods of estimating prevalence, it is independent of AIDS surveillance and is not prejudiced by recent treatment effects on AIDS reporting.^61,78

View larger version (43K): [in this window] [in a new window]   Figure 5 HIV and AIDS projections for England and Wales: homosexual transmission—without and with prevalence gates

The voluntary salivary survey of IDU has provided surveillance for current or prior infection with hepatitis B virus. Testing for other pathogens has begun using sera, starting with hepatitis C in surveys of STD clinic attenders, pregnant women, prisoners and IDU. Permission has also recently been given for testing for hepatitis A and B. This work is facilitated by a STD serum archive of HIV positive and negative specimens exploiting the investment for collection and characterization of specimens.²³

Preparation for detection of new phenomena

A formal independent survey has indicated that regular data from the programmes have proved useful to HIV/AIDS planners.⁷⁹ However the programmes now have to prepare for a changing picture of HIV and AIDS. In the late 1990s the pandemic of HIV is changing with rising prevalence in many Commonwealth countries with links to the UK. These countries account for 60% of prevalent global infections.^80,81 A burgeoning HIV epidemic in India may impact on the south Asian diaspora in the UK as has occurred among the black African community from East Africa.^80,82 The UK's south Asians seem to rarely seek diagnostic HIV testing, and infection emerging among them could take years to manifest as AIDS. However reassurance has come from unlinked data since so far HIV has not appeared in unlinked samples from people born in south Asia attending STD clinics, and low prevalence is observed among pregnant women in districts where there are substantial numbers of south Asians.^44,83 More data are being gathered on global region of birth and ethnic group so as to significantly enhance the surveys.

Monitoring for HIV sub-types

An STD serum archive of HIV positive specimens from the survey represents a unique national resource. The collection of positive specimens, as a well characterized probability sample of diagnosed and undiagnosed prevalence infections overcomes the biases associated with diagnostic testing and asking for referral of specimens. This resource is used for monitoring the epidemiology of HIV-1 sub-types in different risk groups.

Estimating and monitoring incidence

Estimating incidence from serial prevalence data is difficult and prevalence trends can be misleading. For example, among homosexual and bisexual men downward trends followed the referral of men with diagnosed HIV infections out of the STD clinics to specialist HIV care.^85,86 To an extent this bias has been overcome by concentrating on trends in younger men, and men whose infection has not been diagnosed.⁸⁷ The programme has piloted an unlinked anonymous incidence study within its STD surveys which has demonstrated transmission in homosexual and bisexual men of all ages.⁸⁸ However, the methods of identifying recently acquired infections by testing a single specimen promised to add value to the programmes⁸⁹ and this type of technical enhancement is being actively pursued.

Limitations

There are limitations to interpretations of unlinked anonymous programme data. There is an assumption that prevalence in the residual specimens and the patient group are equivalent to the population it is taken to represent (Figure 1). This is not always the case and although patient groups have been chosen to overcome this problem (for example generally avoiding patients with disease, or gathering information so that data from those with disease can be excluded) and adjustments made,⁶⁰ some bias will undoubtedly encroach. This may effect estimates of prevalence but it will not necessarily prejudice trend detection if any bias is constant over time. Certain population groups are not amenable to this form of surveillance; for example, men at general or lower risk of infection because there is no population group having routine blood tests as do pregnant women. Equally there are marginalized groups that are very hard to reach and monitor (e.g. homeless people) because they are poor users of services and do not readily provide stable sample frames. The fact that results cannot be tracked back to the original patients is also limiting as it means clusters of positives and local rises in prevalence cannot be directly investigated. In general therefore the programmes are here best used in combination with other data.

Conclusion

The unlinked programmes have been a good investment (Table 5). The UK programmes plan now runs to 2003/04 reflecting that they are now an essential continuing component in the suite of surveillance methodologies used for surveillance of HIV, AIDS and other sexually acquired infections in the UK.⁹⁰

Acknowledgments

The early development of the programme involved many people notably Sir Donald Acheson, Michael Adler, Julia Heptonstall, John Porter, David Tappin and Richard Tedder. In addition the programme has been enacted by many collaborators who are listed regularly in the annual reports of the programme. The programmes and many of their complementary data sources are supported by public funding through the UK Departments of Health and the Medical Research Council. The First National Survey of Sexual Attitudes and Lifestyles was supported by the Wellcome Trust. Surveillance of HIV infections clinically recognised by obstetricians was supported by the AIDS charity AVERT.

Notes

^d Voluntary testing with informed consent, i.e. following discussion in which the client is aware of the risks and benefits of HIV testing, and his or her explicit agreement to HIV testing.

^e Hereafter referred to as unlinked surveillance or unlinked testing. In the United States the preferred term has been blinded testing.

^f Data from the unlinked programmes and other surveillance sources indicate that infection with HIV-2 is rare in the UK with over 98% of HIV infections detected accounted for by HIV-1. For convenience this manuscript will only refer to HIV but that should be taken to primarily indicate HIV-1.

^g The percentage of all eligible specimens that are from patients asking their specimen be excluded.

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