epidemic in South Africa The evolving HIV epidemic in South Africa Salim S. Abdool Karim, MBChB, PhD and Quarraisha Abdool Karim, PhD

The authors Salim S Abdool Karim, MBChB, PhD, is a clinical infectious diseases epidemiologist whose current research interests are in microbicides and vaccines to prevent HIV infection and implementation of antiretroviral therapy in resource constrained settings. Quarraisha Abdool Karim, PhD, is an infectious diseases epidemiologist whose current research interests are in understanding the evolving HIV epidemic in South Africa; factors influencing acquisition of HIV infection in adolescent girls; and sustainable strategies to introduce HAART in resource-constrained settings. Salim Abdool Karim is Deputy Vice-Chancellor (Research) and Professor of Public Health at the University of Natal in Durban, South Africa. He is also Professor in Clinical Epidemiology at the Mailman School of Public Health at Columbia University and Adjunct Professor of Medicine at the Weill Medical College of Cornell University. He is Director of CAPRISA – Centre for the AIDS Program of Research in South Africa. www.CAPRISA.org Quarraisha Abdool Karim is an Associate Professor of Epidemiology at the Mailman School of Public Health at Columbia University. She is also an Honorary Associate Professor of Public Health and Family Medicine at the Nelson R Mandela School of Medicine, University of Natal, South Africa. She is an Executive Committee member of CAPRISA. In addition, she co-ordinates the Columbia-University Southern African Fogarty AIDS International Training and Research Programme

Learning objectives At the end of this lecture the student will: Be able to define transmission dynamics of HIV Have an understanding of the evolution of the HIV epidemic in South Africa through 5 distinct periods Know the distinct features of the South African HIV epidemic Gain knowledge of the essential interventions against HIV/AIDS.

Transmission dynamics Prevalence - How much disease at a point in time - Existing infected people Implications for health impact Indicates the need for health care Incidence rate - New infections in those without the infection - Rate at which new infections are acquired over a period of time More sensitive for assessing growth of epidemic Sensitive marker of effect of interventions The prevalence and incidence rates are calculated as follows: number of individuals who are infected with HIV at a specific time Prevalence = number of individuals in the population at that point in time number of new cases of HIV during a certain time period Incidence rates = Prevalence reflects the situation at one point in time, while incidence measure the rate at which the infection is spreading. The two measures are complementary ans together provide an understanding of the dynamic changes in an epidemic

South Africa's HIV/AIDS epidemic About 10% of global burden of infection Major and Minor epidemic Distinctive features of major epidemic - Prior to 1987 HIV infection rare in general pop - High prevalence - Highest rates of infection in young women - Predominantly subtype C South Africa is home to about 10% of the global burden of HIV infection. Since the first reported cases of AIDS in South Africa, both a major and minor epidemic has evolved. The minor epidemic was a well circumscribed epidemic caused by subtype B HIV and occurred predominantly in gay men and haemophiliacs. It started in the early 1980s and by 1990 was already on the wane. The major epidemic is caused by subtype C HIV and is spreading heterosexually in the general population. The major epidemic has already reached high prevalence rates in excess of 25% and the highest rates are in young women. Source: Abdool Karim Q, Abdool Karim SS. South Africa: Host to a new and emerging HIV epidemic. Sex Trasm Inf 1999; 75: 139-140 Abdool Karim Q, Abdool Karim SS. Epidemiology of HIV infection in South Africa. AIDS 1999; 13: S4 - S7.

HIV Infection in ANC attendees in South Africa 40 30 HIV prevalence (%) 20 10 Five distinct phases mark the evolution of the HIV epidemic in South Africa: i. Pre-1987: localised clade B epidemic ii. 1988-1993: generalised clade C epidemic starts iii. 1994-1998: explosive epidemic and low mortality iv. 1998 - 2002: Incidence high but stable and mortality rising rapidly v. Post 2002: AIDS-related mortality rates climb until they exceed the HIV incidence rates resulting in an observed decline in HIV prevalence 1988 1990 1992 1994 1996 1998 2000 2002 Source: National Department of Health, Pretoria, South Africa

Introduction of HIV in SA: Pre 1987 1982 – First reported cases of AIDS Epidemic largely limited to: - Men who have sex with men - Transfusion recipients and - Haemophiliacs Clade B The first reported cases of AIDS in South Africa occurred in 1982. This “minor” epidemic was largely limited to men who have sex with men; blood transfusion recipients and haemophiliacs. Infection with subtype B HIV was dominant.

HIV infection in selected groups from 1985 - 1987 Year Province Group N % 1985 KwaZulu Natal Rural community 441 1986 Transvaal Miners 17 021 0.01 Sex workers 1 200 1987 Antenatal women 500 Outpatient 268 Studies in rural and urban communities as well as health care services showed that HIV was rare in the general population prior to 1998. Source: Abdool Karim SS. Making AIDS a notifiable disease- is it an appropriate policy for South Africa? S Afr Med J, 1999; 89: 609-611 Dusheiko GM. Regional prevalence of hepatitis B, delta, and human immunodeficiency virus infection in southern Africa: a large population survey. Am J Epidemiol. 1989; 129(1):138-45.

HIV Infection in ANC attendees in South Africa 40 30 HIV prevalence (%) 20 10 Phase 2: Generalised epidemic begins 1988-1993 The major epidemic as a result of heterosexual spread of HIV is associated with a concomitant epidemic in infants born to HIV infected mothers. The period 1988-1993 marks the beginning of the generalised or “major” epidemic of Clade C HIV infection in South Africa. This exponential increase in HIV infection had a doubling time of approximately 15.1 months. 1988 1990 1992 1994 1996 1998 2000 2002 Source: Department of Health

Age and gender distribution of HIV infection in South Africa 10 Male JUN/JUL 1992 Female 8 6 Prevalence (%) 4 2 Population-based surveys undertaken during this period demonstrate, in addition to the rapid rise in HIV infection, the striking difference in age and gender distribution of HIV infection. The figure illustrates the early rise of infection in young women between the ages of 15-19 years compared to a later rise of infection in men at about age 25-29 years. The high incidence rates in young women is a key factor driving the spread of HIV in South Africa during this period. <9 10-14 15-19 20-24 25-29 30-39 40-49 Source: Abdool Karim Q, Abdool Karim SS, Singh B, Short R, Ngxongo S. Prevalence of HIV infection in Rural South Africa. AIDS 1992; 6: 1535 - 1539

HIV Infection in ANC attendees in South Africa 40 30 HIV prevalence (%) 20 10 Phase 3: Explosive spread of HIV - 1994-1998 The period 1994-1998 is the most critical period in the evolving HIV epidemic in South Africa. This period marks the explosive growth in HIV transmission fuelled by high incidence rates in young women and the coalescence of genetically diverse epidemics. Ironically this period coincided with the establishment of democracy in South Africa. 1988 1990 1992 1994 1996 1998 2000 2002 Source: Department of Health

HIV incidence rates in a cohort of sex workers in KwaZulu-Natal Year Person-months of follow-up Incidence Rate (%); 95% CI 1996/97 996 16.8 (8.0-26.0) 1998 1644 18.2 (11.0-25.0) 1999 780 20.0 (9.0-31.0) Overall (1996-99) 3420 18.2 (13.0-23.0) This period of rapid growth in the HIV epidemic was marked by very high incidence rates. In one trial, follow-up of several hundred sex-workers in the KwaZulu-Natal Province of South Africa showed an average incidence rate of 18.2 per 100 women-years over the period from 1996 to 1999. Source: Abdool Karim SS, Ramjee G and Gouws E – Data from COL-1492 trial

Prevalence and incidence of HIV: Hlabisa clinic attendees aged 15-49: 1992-2001 Year N Prev(%)(95% CI) Incidence % 1992 884 4.2 (3.0-5.7) 2.0 1993 709 7.9 (6.0-10.1) 3.3 1995 314 14.0 (10.4-18.4) 7.1 1997 4731 27.2 (25.9-28.5) 10.2 1998 3166 29.9 (28.4-31.6) 10.5 1999 3001 34.0 (32.5-35.7) 10.3 2001 906 36.1 (32.9-39.2) Data from rural women attending antenatal clinics in one district of KwaZulu Natal Province of South Africa shows the rapid growth in the epidemic during this period, due largely to the high incidence rates creating large numbers of newly infected people within the population. Source: Williams BG, Gouws E, Wilkinson D, Abdool Karim SS. Estimating HIV from Age Prevalence data e epidemic situation. Statistic in Medicine 2000.

Temporal trends in the age-specific prevalence of HIV infection in antenatal clinic attendees in Hlabisa Age Group 1992 1995 1998 2001 20-24 6.9% 21.1% 39.3% 50.8% 25-29 2.7% 18.8% 36.4% 47.2% 30-34 1.4% 15.0% 23.4% 38.4% 35-39 0.0% 3.4% 23.0% This analysis of HIV prevalence in each age group band over 3-year cycles, knows how HIV prevalence grew from 6.9% in 1992 to 50.8% in 2001 among young girls in the rural area of KwaZulu Natal. Source: Wilkinson D, Abdool Karim SS, Williams B, Gouws E. High HIV incidence and prevalence among young women in rural South Africa: developing a cohort for Intervention Trials. J Acquir Immune Defic Syndr 2000; 23: 405-409

HIV Infection in ANC attendees in South Africa 40 30 HIV prevalence (%) 20 10 Phase 4: 1999-2002 The period 1999-2002 epitomises the maturation of the major HIV epidemic in South Africa characterised by the epidemic reaching saturation. The HIV prevalence is almost static, masking the rapidly rising mortality and continued high incidence rates. 1988 1990 1992 1994 1996 1998 2000 2002 Source: Department of Health

Prevalence among antenatal clinic attendees by Province 1999 – 2001 10 20 30 40 KwaZulu- Natal Mpumalanga Gauteng Free State North West East Cape Limpopo Northern Cape Western Cape Province Prevalence (%) 1999 2000 2001 This figure demonstrates the stabilisation of HIV prevalence by province. While KwaZulu-Natal continues to be at the epicentre and the gradient of infection from east to west coast continues, there is stabilisation in HIV prevalence across most of the nine provinces of South Africa. Source: Dept. Health – 12th National HIV and Syphilis Sero-prevalence survey of women attending public antenatal clinics in South Africa 2001

Tuberculosis caseload and antenatal HIV prevalence in Hlabisa district Tuberculosis is the most common presenting opportunistic infection associated with advancing HIV disease. The figure illustrates how the TB burden in one rural community has increased as the HIV prevalence has increased. The high prevalence of HIV infection during this period is indicative of the demand for health care to be anticipated in the next period as individuals progress to AIDS. Source: Hlabisa Hospital Records

AIDS in King Edward Hospital -1998 54% of Medical in-patients were HIV+ 84% of HIV+ met WHO AIDS case criteria 56% HIV+ co-infected with tuberculosis Case fatality rates: HIV+ = 22% vs HIV- = 9% HIV/AIDS now dominates medical practice in South Africa. At a tertiary hospital, more than half the patients were HIV infected in 1998. A case fatality rate has also more than doubled since the pre-HIV era. Source: Colvin M, Dawood S, Kleinschmidt I, Mullick S, Lalloo U. Int J STD AIDS 2001, 386-389

Age specific mortality rate 1985 baseline for men 50 100 150 200 250 300 350 PERCENTAGE OF 1985-1990 AVERAGE 1996-1998 1999-2000 Mortality rates in 1999-2000 are already beginning to rise among men. The increase is predominantly in the 20-40 year age group. 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 AGE Source: Dorrington R, Bourne D, Bradshaw D, Laubscher R, Timæus IM. The Impact of HIV/AIDS on Adult Mortality in South Africa. MRC Technical Report. 2001

Age specific mortality rate 1985 baseline for women 3.500 3.000 2.500 1994 2.000 1996 Ratio 1997/8 1.500 1998/99 1999/2000 1.000 0.500 The situation in women is substantially worse. Mortality rates in young women have quadrupled since the start of the epidemic, especially in young women between the ages of 20-34 years. 0.000 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 Age Source: Dorrington R, Bourne D, Bradshaw D, Laubscher R, Timæus IM. The Impact of HIV/AIDS on Adult Mortality in South Africa. MRC Technical Report. 2001

Conclusion Current epidemic phase has 5 parallel effects: - Continuing large numbers of new HIV infections - Ongoing high mother-to-child transmission rates - Rising morbidity and its impact on health services - Rapidly rising deaths - Increase in numbers of orphans Essential to intervene with: - Prevention of new infections - PMTCT programmes - Care including OI prophylaxis and ARV treatment - Social services for families impacted by AIDS deaths - Programs and social services for orphans

Conclusion HIV affecting mainly young women in SA, highlighting the importance of: - interventions targeting youth - addressing gender inequity - greater involvement of men in prevention programs South Africa is experiencing a devastating epidemic

Acknowledgements Sources of Data - National Department of Health, Pretoria, South Africa - Debbie Bradshaw, South African Medical Research Council - Rob Dorrington, University of Cape Town Brian Williams, WHO, Geneva Eleanor Gouws, WHO, Geneva Cheryl Baxter, CAPRISA