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Patients Unaware of Their HIV Infection Until AIDS Diagnosis in Sweden 1996-2002 - a Remaining Problem in the Highly Active Antiretroviral Therapy Era

Posted on: Saturday, 29 October 2005, 03:02 CDT

By Brnnstrm, J; kerlund, B; Arneborn, M; Blaxhult, A; Giesecke, J

Summary: Our objective was to analyse the characteristics of patients who were unaware of their HIV infection until they developed AIDS, in the period after introduction of highly active antiretroviral therapy. The complete national register of HIV and AIDS cases reported to the Department of Epidemiology at the Swedish Institute for Infectious Disease Control 1996-2002 was searched for cases diagnosed with HIV less than three months before AIDS diagnosis (so-called 'late testers'). Of a total of 487 patients with AIDS, reported during the seven-year period, 219 (45%) were late testers. Their proportion of all AIDS cases increased from 22% in 1996 to 58% in 2002. Heterosexual route of transmission, age greater than 40 years, and foreign origin were all significant risk factors for being a late tester. Intravenous drug users were associated with a highly significant reduced risk.

The group without previously known HIV infection represents an increasing part of all cases of AIDS. From a disease control and from a medical perspective, it is important to study this group further and discover what measures are needed for earlier identification and access to medical care.

Keywords: HIV, AIDS, late tester, delayed diagnosis, Sweden

Introduction

After the introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV in 1996, the rate of progress of the infection towards AIDS and death has decreased dramatically. In Western Europe there has been a reduction in incidence and mortality by more than 60% and 80%, respectively, from 1995 to 2001.1 Even though there should now be a much stronger incentive for people who suspect that they may be at risk of HIV infection to know their status, there still is a group of people who are unaware of their infection until they develop AIDS. Several terms have been used to describe this group of patients; the one we will use is 'late testers'.

The existence of this group, seven years after introduction of modern antiviral combination therapy, shows that all those who should have been subjects of an effective treatment do not receive it. The consequence for the individual is a dramatic life- threatening disease and less-effective eventual treatment.2 For society it indicates a long period of possible contagiousness, during which partners could repeatedly have been exposed. Economically, the late testers represent a considerable medical cost, which to a great extent could have been avoided.

The optimal timing for initiation of therapy in any patient remains imprecisely defined,3 but in any case it should usually be during the asymptomatic phase. Since the median length of the natural latency period is approximately 10 years,4 the existence of late testers should be considered a failure of information dissemination and testing.

We decided to analyse the characteristics of AIDS patients notified in Sweden since the advent of HAART, who had not been diagnosed with HIV infection before they developed AIDS. The aim was to identify common factors associated with the late diagnosis, so that future secondary prevention can be improved. We also wanted to compare the number of late testers with the absolute number of AIDS cases each year to test our hypothesis that the proportion of late testers was increasing. To do this, we undertook a register-based, descriptive epidemiological study.

As in most Western countries, there was a natural peak of notified HIV cases in Sweden with the introduction of HIV testing in 1985. After 1986 there was a marked fall in notified incidence and since 1994 the annual number of reported HIV cases has remained fairly constant around 250. The annually notified number of AIDS cases increased constantly until 1995, after which the number has decreased gradually.

Methods

In Sweden, a country of 8. 9 million inhabitants, voluntary, free, and anonymous HIV testing, coupled to counselling, is available for everyone. Since the beginning of HIV testing there have been several programmes directed towards different high risk groups, such as blood transfusion recipients, haemophiliacs, intravenous drug users (IDUs), including a study in the Stockholm's remand prisons, and homosexual men. There are also more general, national screening programmes for pregnant women and blood donors.5,6

Since 1985 there has been a mandatory, anonymous case reporting of HIV and AIDS in Sweden. A patient is reported once when the HIV infection is diagnosed and again when AIDS has developed. The latter diagnosis is based on the 1993 Expanded European AIDS case definition.7 cases are reported with a non-unique patient code to the Department of Epidemiology at the Swedish Institute for Infectious Disease Control (EPI/SMI), where they are registered in a database. Six months after the initial case report, a questionnaire is sent to the patient's physician. This questionnaire collects additional information about the patient, especially concerning country of origin and route of transmission, which is subsequently entered into the same database.

From this register, all reported cases of AIDS in Sweden during the period 1996-2002 were identified. A 'late tester' was defined as a patient with AIDS where the time interval between first positive HIV test and AIDS diagnosis was ≤3 months. This time interval was chosen since it has been used in previous studies8,9 and also because it was regarded as long enough to cover any possible delay in AIDS diagnosis due to mycobacterial culture, etc. All patients who had a time interval greater than three months between HIV and AIDS diagnosis were called 'non-late testers'. The reason to include cases only from 1996 and onwards was because this was the year when protease inhibitors where routinely introduced.

All children under the age of 15 (in total five) were excluded. Eight persons who were initially assigned to the late testers group were later re-assigned, as non-late, due to additional information from the questionnaire mentioned above, indicating that the HIV diagnosis was known earlier (due to HIV diagnosis in another country, HIV report using alternative coding, etc).

The two groups of patients were compared regarding sex, age, nationality and route of transmission. Tests for significant differences in proportions were performed using χ^sup 2^ analysis, or, when numbers were small, by Fisher's exact test. Tests for significant age differences between groups were performed with Wilcoxon's test.

Results

During the period 1996-2002, 487 AIDS cases older than 15 years were reported in Sweden. Out of these almost half, 219 (45%), were previously unaware of their HIV infection. Though the absolute number of late testers has been fairly constant, around 30 each year, this group represents an increasing proportion of the total number of AIDS cases. From having been just above 20% at the beginning of the study period, they now make up almost 60% (Figure 1).

The sex distribution was roughly the same among late and non- late testers, with approximately 75% being men in both groups (Table 1).

Median age for men at AIDS diagnosis was 42 (23-90 years) for the late testers and 33 (17-67 years) for the non-late (P < 0.0001). For women, the corresponding figures were 32 (21-65 years) and 30 (17- 64 years), respectively; this difference is not significant. Average time from HIV to AIDS diagnosis among the non-late testers was 7.5 years for men and seven years for women.

Reported routes of transmission differed little between the two groups, but for one clear exception. Among the late testers only six out of 219 (3%) were IDUs, compared with 59 out of 268 (22%) among the non-late testers. This difference is highly significant (P < 0.001).

Heterosexual transmission was predominant in both groups, but more common among late testers. The increased risk of being a late tester, among those with a heterosexual route of transmission compared with the others, is also significant (P < 0.01). Of all the groups, the group with an unknown mode of transmission was the one with the largest proportion of late testers, 81% (13/16).

Figure 1 AIDS cases in Sweden in 1996-2002 divided into 'late' and 'non-late testers'. Absolute numbers on the Y-axis

Table 1 Characteristics of 'late' and 'non-late' testers diagnosed with AIDS in Sweden 1996-2002 ('late tester' is defined as a person who is diagnosed with AIDS ≤ 3 months after the first HIV diagnosis)

The majority of incident AIDS cases -non-late as well as late - during the study period, were people of Swedish origin infected in Sweden. However, immigrants represented an increasing proportion. Especially among late testers, there was a steady increase over the seven-year period (Figure 2). From having represented approximately a quarter of the late testers in 1996, immigrants constituted over 50% by 2002. The absolute number of immigrants with AIDS is not increasing, but their increasing proportion is due to a decreasing trend in AIDS incidence among Swedish-borne patients.

Being infected in Sweden was associated with a statistically lower risk of being diagnosed late, compared with others (P < 0.001). However, for Swedish citizens infected abroad the opposite held (P < 0.002). Though the to\tal number of such patients has been fairly constant over the years with a slightly decreasing tendency - a larger proportion of Swedish citizens infected abroad were being diagnosed late; at the end of the period as many as 70%.

Among all AIDS cases during the study period who were infected in Sweden, the majority (110/ 215, or 51%) were men who had had sex with men (MSM), compared with only 17% who reported a heterosexual route of transmission. Looking at Swedish citizens infected abroad, the situation was the opposite: 35% (29/84) were MSM and 61% (51/ 84) heterosexuals. In the latter group there was a clear predominance of men, 88% (74/84). While MSM infected abroad were as likely to be a late, as a non-late, tester, more than two-thirds (71%) of heterosexual men infected abroad were getting a late diagnosis. Out of these, two-thirds were infected in Asia, whereas MSM were mainly infected in Europe.

Figure 2 Late testera in Sweden in 1996-2002 by origin. Absolute numbers on the Y-axis

Discussion

Since the beginning of the HIV epidemic, persons who are unaware of their HIV status prior to developing AIDS have constituted a special problem. Several studies were conducted before the HAART era, for example, in England,10,11 Wales,10 France,12 Australia9 and the USA,13 showing figures of late testers ranging from 18% to 43% of all AIDS cases. The latter figure was derived from a study defining a late tester as someone having received HIV and AIDS diagnosis within nine months, a considerably wider definition than used in our study. In the French12 study, being heterosexual, male, and above 35 years of age were associated with a higher risk of late diagnosis. The American study13 found a higher risk for heterosexuals and IDUs. The English/Welsh10 study identified heterosexuals, persons over 50 years of age, and 'non-whites' as being at higher risk, whereas a study from St Mary's Hospital in London,11 a few years later, found no significant difference between an early and late testing group of patients, other than their 'AIDS defining illness'.

The fact that late testers still exist in the era of HAART is puzzling. Three studies conducted during the change-over in therapy (1986-98, 1992-98 and 1994-2000), from Rome,8 Victoria (Australia),14 and Spain,15 respectively, all show figures consistent with ours: the group with previously unknown HIV infection represents an increasing proportion of all AIDS cases. At the end of the study periods, the proportion of late testers seen in these studies ranged from 35% up to the 60% seen in our material. In USA, a similar study from 16 sites in 2000-03(16) showed that approximately 50% of AIDS patients received their diagnosis within the same year as they were diagnosed with HIV.

Together with the Spanish study, the present study is - to our knowledge - the only national study of late testers after the introduction of HAART. They both have the strength of being based on a central reporting system, and, whereas HIV infection is not a notifiable disease in many countries, Swedish physicians are obliged to report both HIV and AIDS, separately. This minimizes the risk of missing cases of HIV and gives us a reliable figure of the time from first positive test to the development of AIDS. One weakness of our study and of the Swedish reporting system - is that if a person who gets tested anonymously for HIV turns up several years later with AIDS, without disclosing the previous test, we will never know about it. In a similar way, we may not always be aware of immigrants having had previous tests in their country of origin.

Looking at our figures, immigrants represent the largest and still increasing proportion of late testers. In Sweden almost all immigrants are entitled to a free medical examination on arrival, but to what extent this examination is performed and includes HIV testing, in particular, is unknown. Furthermore, for several of the patients, the exact date of entry into Sweden is not recorded. We thus do not know what proportion of our cases were missed by the Swedish health care system and what proportion had AIDS already on arrival in Sweden. As mentioned earlier, unknown HIV tests in their country of origin, or simple lack of available HIV-testing facilities, may lead to an overestimation of the risk of being defined as a late tester among immigrants in our study. However, foreign origin appears as a risk factor for being a late tester in all the above-mentioned studies conducted after the introduction of HAART.8,14-16 Cultural barriers, alienation, and language difficulties are factors discussed that all are of importance. Without question, further steps to increase awareness and active testing are required in order to decrease late testers in this group.

IDUs represent a group in which awareness of HIV is high, and the risk of infection is also well appreciated by health-care workers. This awareness means that, with few exceptions, they are diagnosed with HIV long before becoming symptomatic with AIDS. In our study, there was less than one IDU per year among the late testers. IDUs were therefore diagnosed earlier than homo- and bi-sexual men, who were, however, more likely to get an early diagnosis than heterosexuals (Figure 3). The reduced risk of being diagnosed late among IDUs is also shown in the study from Spain15 and Rome.8 The latter, as well as the Australian and American study,14,16 also find an increased risk for heterosexuals. Of special interest in our study, and perhaps of international importance, is the fact that of Swedish-borne men heterosexually infected abroad more than two- thirds are ignorant of their HIV infection until AIDS diagnosis.

Figure 3 Late testers in Sweden in 1996-2002 by route of transmission. Absolute numbers on the Y-axis (MSM = men who have sex with men, IDU = intravenous drug users)

The male late testers were almost 10 years older than the male non-late testers, whereas there was no difference for women. This difference is almost entirely due to the women infected before immigration being younger. The fact that an AIDS case, older than 40 years, has a significantly higher risk of being a late tester indicates that the risk of infection among the elderly is being underestimated. This has also been shown in previous studies.8,14,15

The decreasing total number of AIDS cases is, without question, a result of effective antiretroviral therapy introduced in 1996. That the number of late testers, in spite of this progress, remains constant indicates that the understanding of the importance of early diagnosis and treatment in combating HIV infection among a broad spectrum of the population is poor.

The fact that studies, irrespective of their size, in varied countries like Sweden, Spain, Italy, Australia, and USA, show similar results is not only interesting but also gives a clear message: the previous classical risk groups for undiagnosed HIV infection must be re-evaluated. General education about - and awareness of - the disease, which was high at the beginning of the epidemic in the mid80s, must be maintained and continually updated.

References

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16 Centres for Disease Control. Late versus early testing of HIV - 16 sites. United States, 2000-2003. MMWR 2003;52:581-6

(Accepted 15 June 2000)

J Brnnstrm MD1, B kerlund MD PhD1, M Arneborn RN2, A Blaxhult MD PhD1,2 and J Giesecke MD2,3

1 Department of Infectious Diseases, Karolinska University Hospital, Stockholm; 2 Department of Epidemiology, Swedish Institute for Infectious Disease Control (E\PI/SMI), Stockholm; 3 Department of Medical Epidemiology and Biostatistics, Karolinska Institute Medical University, Stockholm, Sweden

Correspondence to: Dr Johanna Brnnstrm

Email: johanna.brannstrom@karolinska.se

Copyright Royal Society of Medicine Press Ltd. Oct 2005

Source: International Journal of STD & AIDS

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