H H H HI I I IV V V V A A A AN N N ND D D D A A A AI I I ID D D DS S S S I I I IN N N N S S S SP P P PA A A AI I I IN N N N, , , , 2 2 2 20 00 01 1 1 1

Edited and distribuyed by: © MINISTERIO DE SANIDAD Y CONSUMO CENTRO DE PUBLICACIONES Paseo del Prado, 18. 28014 Madrid NIPO: 351-02-027-7 Depósito Legal: M-24045-2002 Printed: Rumagraf, S.A.

Avda. Pedro Díez, 25. 28019 Madrid Printed in Spain O.T. 31484

BACKGROUND Spain is a country in southern Europe with a population of about 40 million inhabitants. In the 1990s, it was the European country most heavily affected by the HIV/AIDS epidemic, but this situation has changed in recent years, as great progress has been made in controlling HIV transmission, and AIDS incidence and mortality rates have been substantially reduced. The epidemiological situation of HIV infection and AIDS in Spain at the start of the 21st century is the result of a process of over 20 years, which can be briefly summarized in three major events:1 The rapid spread of HIV during the 1980s.

During this decade HIV infection spread widely among a large number of injecting drug users (IDUs)2,3 in Spain, making this mechanism of transmission responsible for more than two-thirds of cases. HIV also spread among homosexual men, although much less abruptly.4,5 The high number of HIV-infected IDUs, most of them sexually active young adults, led to secondary transmission of HIV by the heterosexual and perinatal route. At the start of the 1990s, more than 100,000 HIV infections had already occurred,6 and AIDS-related mortality ranked first among the major causes of potential years of life lost in Spain.8 The progressive control of HIV transmission since the beginning of the 1990s.

The seriousness of the situation alerted society. New prevention programs were started and existing programs intensified, which helped to reduce risk practices. The number of young people in the next generations started intravenous drug use gradually decreased,9 resulting in a gradual aging of the IDU group. Added to this was a trend to replace the intravenous route of drug use by the inhaled or smoked route.9,10 These trends led to a marked reduction in the rate of occurrence of new HIV infections, as has been shown by serial studies of HIV seroprevalence in IDUs,11-12 homosexual men3,5 and women who engage in sex work.13-14 The spread of highly active antiretroviral therapies since 1997.

By the mid-nineties, the highest point in the epidemic in terms of morbidity and mortality was reached, with more than 7,000 new AIDS diagnoses and more than 5,000 deaths annually.3 Since highly active antiretroviral therapies were introduced at the end of 1996, there has been a considerable improvement in the immune status and prognosis of HIV-infected persons.15 This resulted in a rapid reduction in AIDS incidence of over 60% in the next four years, and a decline in mortality of 67% in just two years.3 HIV AND AIDS IN SPAIN, 2001 3

STATUS OF THE EPIDEMIC IN SPAIN AT THE BEGINNING OF THE 21ST CENTURY • HIV TRANSMISSION General trend The various sources of information available agree in pointing out a steady decline in HIV transmission rates in Spain over recent years.4-5,11-14 However, the number of new HIV diagnoses is still high, and the possibility of new increases in transmission rates cannot be ruled out.16 In autonomous communities in which epidemiological data on newly diagnosed cases of HIV infection is available, a reduction of over 70% has been noted since the early 1990s.17 In spite of this large decrease, an overall total of 60 new HIV infections per million inhabitants were diagnosed in these communities in 2001, a figure that is still very high in comparison with other European countries (Figure 1).7 The risk of HIV infection is distributed very heterogeneously in the population.

In Spain, the situations associated with the highest risk of infection are, in order of importance, parenteral drug use, homosexual practices between men and heterosexual contact with an infected partner. In spite of this, risky sexual relations have been the leading cause of new infections in recent years, which is explained by the fact that it is the most widespread exposure to risk in the population (Figure 2).18 4 HIV AND AIDS IN SPAIN, 2001 50 100 150 200 250 1994 1995 1996 1997 1998 1999 2000 2001 Year Diagnosis of HIV-infection per million inhabitants Spain* Belgium Germany Ireland Switzerland United Kingdom *Three regions.

Figure 1. Time trend of HIV diagnosis in several European countries.

Figure 2. New diagnosis of HIV-infection,according to transmission category in three Spanish regions. 100 200 300 400 500 600 700 800 1986 1988 1990 1992 1994 1996 1998 2000 Year Number of HIV diagnosis Injecting drug users Sexual transmission

Injecting drug users Large changes have occurred in this group over the years, which have led to a rapid and marked reduction in the number of new HIV infections.9,11-12 Of these, the most important change has been a steady decline in the number of youths starting intravenous drug use and, consequently, in the risk of infection by this route.19-20 In parallel to this, some former IDUs, mostly heroin users, have stopped consuming and many others have switched either partly or totally from the injected to the inhaled route (Figure 3).21 This process has not occurred simultaneously or with the same intensity throughout Spain.10,21 The risk of HIV infection continues to be very high among persons who inject drugs, although various studies have found moderate reductions in prevalence (Figure 4),10-12,22 probably contributed to by the spread of methadone maintenance and needle exchange programs.9,23 Men who have sex with men European statistics on AIDS cases show that Spain is one of the countries with the highest rates in homo/bisexual men.7 HIV seroprevalence in homo/bisexual men declined in the first half of the 1990s, but subsequently has remained stable at around 10% (Figure 5).4-5,24 In other European countries, there have been recent reports of increases in risk practices,25 incidence rates of sexually transmitted diseases,26 and the incidence of HIV in homosexual men.27 This new trend may also be HIV AND AIDS IN SPAIN, 2001 5 Figure 3.

Main route of drug administration among persons first time attended for heroine or cocaine dependence.

10 20 30 40 50 60 70 80 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Percentage Injected Smoked/inhaled Sniffed Elaborated from Treatment indicator of the Spanish Observatory on Drugs. DGPNSD. Figure 4. HIV infection among injecting drug users who were voluntarily tested. 38,4 33,1 28,9 27,9 28,2 23,9 25 30,7 22,2 5 10 15 20 25 30 35 40 45 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year 50 100 150 200 250 300 350 Number of HIV+ Prevalence (%) Nº of HIV+ The EPI-VIH Study. Prevalence (%)

occurring in Spain, as reflected by a recent study in Madrid, which found an upward trend in HIV transmission since 1997 in a cohort of men with homosexual practices.16 Recent studies have found that men who have sex with men, male sex workers and transvestites are groups especially susceptible to HIV; furthermore, it is worth noting that nearly half of the men in these groups are of Latin American origin.28-30 Heterosexual transmission of HIV HIV transmission through heterosexual contacts has remained an endemic phenomenon in Spain, without appreciable changes.

However, the level of endemicity has been relatively high compared to other European countries, as is revealed by comparison of the AIDS rates in this transmission category.7 The marked decrease in other mechanisms of HIV transmission in Spain has caused heterosexual transmission to become the leading cause of infections in recent years, although this does not imply an increase in the number of infections by this route.

The heterosexual population is very heterogeneous in terms of the risk of HIV infection. The data that probably best summarize this situation are those for seroprevalence in women delivering a liveborn child, which ranges from 1 to 3 per 1000, although there are differences between autonomous communities.24,31 Among persons who only have heterosexual exposure, the highest risk of HIV infection is found in those with an infected sexual partner, most of which are IDUs or ex-IDUs. Over the years, this group has shown infection prevalence rates of over 5%, with no clear signs of a decrease (Figure 6).32 In women engaging in sex work, HIV seroprevalence has fallen below 2% (Figure 7), and intravenous drug use has become an uncommon practice.13,14,32 A massive influx of immigrant women from Latin America, sub-Saharan Africa and Eastern Europe has occurred in recent years in this group; however, an increase in levels of infection has not been observed to date.28,32 6 HIV AND AIDS IN SPAIN, 2001 Figure 5.

HIV infection among homo/bisexual men voluntarily tested.

1992 1993 1994 1995 1996 1997 1998 1999 2000 Year Number of HIV+ Prevalence (%) Nº of HIV+ The EPI-VIH Study. Prevalence (%) 19,6 15,6 11,1 13 10 10,3 8,8 10,4 8,3 5 10 15 20 25 50 100 150 200 250

New diagnoses of HIV infection reflect moderate decreases in the number of infections from heterosexual transmission,17 which agrees with the lower frequency of sexual risk behaviors in the Spanish population compared to other countries,33 and the continuous decrease in the incidence of sexually transmitted diseases during the 1990s.34 Mother-to-child transmission Spain was the European country with the highest incidence of AIDS through mother-to-child transmis- sion.7 The high effectiveness of antiretroviral therapy in reducing the rate of mother-to-child HIV transmission led to it being proposed as a goal to virtually eliminate infections transmitted by this mechanism, for which early diagnosis of infection in all pregnant women is a prerequisite.

In recent years, between 500 to 1000 HIV- infected women have delivered a liveborn child in Spain but, thanks to new treatments, it is estimated that the number of children born with HIV infection is well below 40.31 The number of HIV infections and AIDS cases in children of infected mothers has been markedly reduced (Figure 8),3 but still shows that there is a long way to go for complete control of this mechanism of transmission. HIV AND AIDS IN SPAIN, 2001 7 Figure 6. HIV seroprevalence among persons with HIV infected heterosexual partner. The EPI-VIH Study.

8,5 10,6 9,9 10,6 9,3 12,4 10,5 10,3 7,9 2 4 6 8 10 12 14 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year Prevalence (%) Figure 7. HIV seroprevalence among female sex workers voluntarily tested. The EPI-VIH Study. 8,4 5 4 2,4 2,8 0,6 1,8 1,3 0,8 2,5 1,4 1,3 1 1,3 0,3 1,3 0,9 0,7 2 4 6 8 10 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year Prevalence (%) TOTAL Non injecting drug users

HIV infection and immigrants Of the AIDS cases diagnosed in Spain up to 2001, less than 3% were persons from other countries of origin, which reflects the fact that AIDS epidemic has mainly affected the national population.3 In recent years, progressive control of HIV transmission in the Spanish population, together with a growing influx of immigrants to Spain, has caused this characteristic of the HIV epidemic to be reversed.

The fact that some immigrants come from countries where HIV/AIDS is highly endemic may have some impact, but it is likely that adverse social conditions, leading to situations of greater vulnerability to HIV infection, such as prostitution or drug use, and greater difficulty to access prevention measures and health services, play a more important role.35-36 As was previously described for other countries in Europe, the growing importance of immigrant populations in the HIV epidemic has also started to become evident in Spain. In all autonomous communities that have data on newly diagnosed AIDS cases, over 20% of the persons diagnosed with HIV infection in 2001 were immigrants, a percentage which has doubled in just two years.37 Nevertheless, HIV prevalence rates in immigrants who underwent voluntary testing have not been higher than those found in a Spanish population of similar characteristics, except in women from sub-Saharan Africa and men from Latin America.28 This new trend has begun to have impact on the number of AIDS cases (Figure 9), in which there is an increasing proportion of persons 8 HIV AND AIDS IN SPAIN, 2001 Figure 9.

Number and percentage of AIDS cases in Spain in persons from other countries of origin. 50 100 150 1 9 8 9 1 9 9 1 9 9 1 1 9 9 2 1 9 9 3 1 9 9 4 1 9 9 5 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 Year Number of AIDS cases 2 4 6 8 10 Percentage of all cases Number ofAIDS cases Percentage of allAIDS cases Figure 8. Mother-to-child transmitted AIDS cases in Spain.

20 40 60 80 100 1985 1987 1989 1991 1993 1995 1997 1999 2001 No. of new AIDS cases AZT recomendation to HIV-infected pregnant women Proteasa inhibitors Year

with a country of origin other than Spain, mainly Africa, Latin America and Portugal.3 Diagnosis of HIV infection and AIDS in persons from other countries does not mean that they were already infected when they arrived; as at least a third of immigrants diagnosed with AIDS in Barcelona may have acquired the infection in Spain.38 • NUMBER AND CHARACTERISTICS OF PERSONS LIVING WITH HIV INFECTION The key feature of the current situation of the epidemic in Spain is the existence of a high number of persons living with HIV infection (Table 1).

Advances in antiretroviral therapy have improved survival considerably, but have been unable to achieve a cure, making HIV infection a chronic disease. New therapies have improved the quality of life of HIV-infected persons, although, once started, treatment must be maintained on an indefinite basis. HIV prevalence in the general population is approximately 3 infections per one thousand inhabitants, increasing to 6 per thousand in the 20 to 39 years age group.6,39 In line with the general pattern of the epidemic, seroprevalence in men is three times higher than in women. In mothers of newborns, i.e., in sexually active women of childbearing age, seroprevalence rates range from 1 to 3 per thousand in most autonomous communities.24,31 HIV AND AIDS IN SPAIN, 2001 9 Persons living with HIV infection 110,000 – 150,000 Prevalence of HIV infection (rate per 1000 inhabitants) 2.7 – 3.8 Probable mechanism of infection in persons living with HIV Injecting drug users 50% - 60% Men with homosexual practices 15% - 25% Heterosexual risk 20% - 30% Characteristics of persons living with HIV Men 75% - 80% Women 20% - 24% Children (under 13 years) < 1% Persons developing AIDS since the start of the epidemic* 65,000 – 75,000 New AIDS diagnoses in 2001* 2,500 – 3,000 AIDS incidence rate in 2001 (per 100,000 inhabitants)* 6.3 – 7.5 HIV/AIDS deaths since the start of the epidemic* 40,000 – 50,000 Persons living with HIV-hepatitis C coinfection 60,000 – 80,000 Table 1.

End-2001 estimates of the HIV/AIDS epidemic in Spain. * Estimates take into account underreporting.

Based on this seroprevalence data, there are an estimated 110,000- 150,000 persons living with HIV infection in Spain, although probably more than a quarter of them have not yet been diagnosed (Figure 10). In recent years, the population of persons living with HIV infection has remained relatively stable, since both the number of new infections and the number of deaths in infected persons have fallen to low levels.40 The epidemiological characteristics of these persons depend less on new infections than on those that have accumulated over the course of the epidemic. These characteristics can be approximated by studying the number of AIDS cases diagnosed in recent years3 or the number of patients with HIV infection reported in hospital surveys, as both figures arise directly from the population of persons living with HIV infection.

Based on either of these sources, we can estimate that a little more than half (50-60%) of HIV-infected living persons acquired the infection by sharing parenteral drug injection equipment, 20-30% from unprotected heterosexual practices and 15- 25% are men who became infected through unprotected homosexual practices. The proportion of men to women is approximately 4:1, and the average age of these persons is from 35 to 40 years, with a progressive trend toward aging.

The high frequency of intravenous drug use among persons living with HIV in Spain explains why more than half of them are also infected by hepatitis C virus. • REDUCTION OF HIV/AIDS MORBIDITY AND MORTALITY Most persons with HIV infection will tend to progress to AIDS if the natural course of the disease is allowed to go unchecked, resulting in high levels of morbidity and mortality from AIDS. Highly active antiretroviral therapies have changed this situation, dramatically improving the prognosis for infected persons.41 Following their introduction in 1997, they caused very sharp decreases in the incidence of AIDS and mortality (Figure 11).

In recent years, these decreases have become less pronounced, which leads us to suspect that the ceiling for their effectiveness may have been reached.3 In 2001, the lowest AIDS rates in the last ten years were recorded in Spain (5.8 new AIDS cases per 100,000 inhabitants), but despite this significant advance, they 10 HIV AND AIDS IN SPAIN, 2001 Figure 10. Estimated time trends of HIV epidemic in Spain.

20000 40000 60000 80000 100000 120000 140000 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 Year No. of persons Persons newly infected with HIV HIV related deaths Persons living with AIDS

were still high compared to other European countries, making Spain the second ranking country in the AIDS incidence rate, only surpassed by Portugal.7 Antiretroviral therapies currently play a fundamental role in continuing to reduce morbidity and mortality from HIV/AIDS and in preventing AIDS incidence and mortality from recovering past levels, since the number of HIV-infected living persons is still very high.

The main factors hindering greater impact of antiretroviral therapies are: late diagnosis of AIDS leading to delays in the start of treatment,42 lack of patient compliance with treatment, the emergence of resistance to antiretroviral drugs and adverse reactions requiring prescribed treatments to be withdrawn or changed.

Delayed diagnosis of HIV infection has been shown to be an important factor in reducing the impact of antiretroviral therapies,42,43 and probably of preventive measures as well.44 Its importance is illustrated by the fact that of all persons diagnosed with AIDS since 1998, over a third did not know they were infected by HIV, and this proportion exceeds 50% in AIDS cases due to sexual transmission (Figure 12). Improved life expectancy in HIV- infected persons is providing the opportunity for other late- developing health problems to appear. The most notable case of this is infection by hepatitis C virus, the high frequency of which in HIV- infected persons is leading to an increasing incidence of chronic liver disease and cirrhosis.

HIV AND AIDS IN SPAIN, 2001 11 Figure 11. Time trend in AIDS incidence and mortality in Spain. 2000 4000 6000 8000 1985 1987 1989 1991 1993 1995 1997 1999 2001 Year Number of persons New AIDS cases AIDS deaths Expanded AIDS case definition Highly active antiretroviral therapy Figure 12. AIDS cases unaware of their HIV infection up to AIDS diagnosis, 1998-2001. 35,6 17,3 56,3 59 0 10 20 30 40 50 60 70 TOTAL Injecting drug users Homo/bisexual men Heterosexual category %

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