MALAWI MEDICAL JOURNAL; 18 (3):99-121 September 2006

Epidemiology of HIV/AIDS in adults in Malawi Eveline Geubbels1 and Cameron Bowie Center for Reproductive Health, Department of Community Health, College of Medicine, Malawi Department of Community Health, College of Medicine, Blantyre, Malawi 1. Current affiliation: International Antiviral Treatment Evaluation Center, Pietersbergweg 9, 1105 BM, Amsterdam and Projet Ubuzima, Rue Akagera 716, PO Box 4560, Kigali, Rwanda; 00250 08672971, [email protected].

General introduction Methodology of this review We searched for references of published literature about Malawi through Pubmed and obtained full text papers from HINARI, Popline, EBSCO, journals´ open access initiatives, local libraries, and – through the gratefully acknowledged help of Dr. Ian Holtby - libraries in the UK. Non peer-reviewed published documents were obtained from the documentation centres of the Ministry of Health, National AIDS Commission, College of Medicine and UN and through Popline. Local researchers were contacted to provide additional grey literature. The Cochrane library was used (through HINARI and the free WHO Reproductive Health Library) for information on the current state of effective interventions for HIV/ AIDS.

malignancies and is the hallmark of Acquired Immune Deficiency Syndrome (AIDS). The rate at which the immune system is destroyed is directly related to the rate of viral replication. During acute HIV infection, viral load is high because replication occurs in the absence of an immune response. CD4 count drops and about half of recently infected individuals will experience a non-specific viral illness, characterized by fever, sweats, malaise, myalgia, pharyngitis, gastrointestinal disturbance, headache, generalised lymphadenopathy and hepatosplenomegaly. Transmission risk is high during this period. After the immune response has developed, the viral load drops to a plateau and CD4 count increases (but not to pre-HIV levels) and then slowly declines over the years until it reaches such a low level that opportunistic infections and malignancies develop.

We made extensive use of Yolande Coombes’ review on sexual and reproductive health behaviour in Malawi that was used as input for the national BCI strategy for paragraph 3.2 (behavioural determinants) and 3.3 (structural determinants).1

About 5-10% of people are rapid progressors, who develop AIDS within one to two years following HIV infection. This is associated with high levels of viral replication and a steep decline in CD4 count. Another 5-10% are able to control HIV very effectively. These Virological, immunological and pathogenic aspects of long-term non-progressors, who sometimes have been HIVb infected for more than 20 years, have very low viral loads Human Immunodeficiency Virus type 1 (HIV-1) is the and competent immune systems. However, the majority virus responsible for the global HIV pandemic, whereas of HIV infected people in developed countries, when not the less pathogenic HIV-2 is largely restricted to West on antiretroviral therapy, progress from HIV infection to Africa. Within the HIV-1 type, subtypes A, C and D are AIDS in 8-10 years. There is some evidence that poor most common in Africa, with subtype C estimated to be socio-economic conditions, including malnutrition and responsible for 90% of infections in southern Africa. limited access to health care, may contribute to a 1-2 year HIV primarily infects and destroys cells in the immune shorter latent period in developing countries. system, particularly CD4+ T-lymphocytes. The immune system is not able to eliminate the HIV virus, although it may control viral replication to some extent through The final progression to AIDS is characterised by very humoral and cellular immune responses. Because it cannot low CD4 counts and rising viral load, thus leading to remove the antigen, the immune system remains highly increased transmission risk in this period. The stage of activated and in the process burns out and falls apart. the immune function in HIV infected individuals can be This degeneration of the immune system over the years clinically assessed, using the standardised criteria of the results in increased risk of opportunistic infections and WHO Clinical Staging System (table 1). Malawi Medical Journal: Special Edition on Burden of Disease in Malawi I

112 The Epidemiology of HIV in Malawi

Diagnosis and monitoring of HIV2

Diagnosis In most contexts, HIV infection is diagnosed by detecting antibodies against HIV, e.g. through enzymelinked immunosorbent assay (ELISA), Western Blot or rapid test devices. However, antibodies against HIV only become detectable in blood from approximately 4 weeks after infection. Tests for the virus itself reveal infection earlier. The p24 antigen test, which targets one of HIV’s core proteins, is positive in the majority of patients a week before an antibody ELISA test becomes reactive. Polymerase Chain Reaction (PCR) testing, which targets a portion of the HIV RNA or DNA, can detect HIV two weeks before ELISA and is best way at the moment to measure viral load. HIV can also be grown in cell culture. The third-generation ELISA-tests have a sensitivity approaching 100% and specificity > 99%. Used correctly, rapid tests have an accuracy closely approaching that of ELISA tests.

WHO Stage 3 - More than 10% weight loss - Chronic diarrhoea for > 1 month - Prolonged fever for > 1 month - Oral candida, chronic vaginal candidiasis - Oral hairy leukoplakia - Severe bacterial infections - Pulmonary TB - Performance status 3 (in bed < 50% of past month)

WHO Stage 4 (AIDS) - Extrapulmonary TB - Pneumocystis Jirovecii Pneumonia (PcP) - Cryptococcal meningitis - Herpes simplex virus ulcer > 1 month

The p24 test and culture are mainly used in research, not in routine clinical settings and have been largely superseded by PCR. In resource poor settings none of these tests are routinely available.

- Oesophageal or pulmonary candidiasis

Malawi relies on two different rapid tests for diagnosis of HIV in individuals, as per WHO testing recommendations for regions where HIV prevalence exceeds 10% and ELISA for quality control purposes and research. Single ELISA tests are used for ANC sentinel surveillance, in accordance with the recommendations of WHO on HIV testing for surveillance purposes.

- Cytomegalovirus (CMV) (other than liver,

Table 1. World Health Organization clinical staging system WHO Stage 1: - Seroconversion illness - Asymptomatic infection - Persistent generalised lymphadenopathy

- Cerebral Toxoplasmosis - Extra-pulmonary Cryptosporidiosis - Isosporiasis

spleen, or lymph nodes) - HIV wasting syndrome - HIV encephalopathy - Kaposi’s sarcoma (KS) - Progressive multifocal leukoencephalopathy - Disseminated endemic mycosis - Atypical mycobacteriosis - Non-typhoid Salmonella bacteraemia - Lymphoma - Performance status 4 (in bed > 50% of past month)

- Performance status 1 (fully active and asymptomatic)

Monitoring WHO Stage 2 - Less than 10% weight loss - Herpes zoster - Minor mucocutaneous manifestations - Recurrent upper respiratory tract infections - Performance status 2 (symptomatic but near fully active)

To keep track of the progress of HIV disease, CD4 count and viral load are used. Viral load predicts the rate of disease progression and CD4 count indicates the stage of disease the patient has reached. Viral load tests measure the concentration of free virus in the blood plasma, in the form of HIV RNA. A viral load change of more than a 0.5 log10 copies/ml (i.e. a factor 2) is significant. These tests can be used when deciding to start therapy or for monitoring the response to therapy. Malawi Medical Journal: Special Edition on Burden of Disease in Malawi I

The Epidemiology of HIV in Malawi 113

CD4 cells are detected using monoclonal antibodies to the CD4 molecule. Adults with normal immune function have a CD4 count of > 1000 cells/μl. Levels of 200-500 cells/ μl, < 200 cells/μl and < 50 cells/μl constitute moderate, advanced and severe immune suppression respectively. As of now, CD4 and viral load testing is available only in referral hospitals and research laboratories in Malawi.

Distribution of disease Incidence of HIV The first documented case of HIV-1 in Malawi occurred in 1982, as molecular epidemiological analysis of stored blood spot from the Karonga Prevention Study has shown3. From 1982 to 1984 subtypes A, C and D were all present. By 1987 to 1989, subtype C had become the predominant subtype and AC, AD and DC recombinants had emerged. This study supports the general notion that HIV-1 subtype C spread from Central Africa to East and Southern Africa.

less afflicted by factors like widowhood, divorce and STI associated with fertility and HIV). Overall, in subSaharan Africa, ANC data overestimate the risk in men and underestimate the risk in women.7 Crampin and colleagues confirmed that this was indeed the case in Karonga district.8 Directly standardised estimates of men and women from ANC data were 9.4% and 9.2 % versus 11.4% and 13.9% in the community. The prevalence of HIV among sexually active women in Karonga who did not attend ANC was 27%, against 12% in ANC women.12

The differences between ANC and community results in the Karonga study8 were mainly the result of sociodemographic factors like age, area of residence, marital status and moving household, but fertility differences have been important in other studies.7 This underscores the need to carefully adjust ANC data before making extrapolations to the general population, and Information about incidence of HIV (number of new emphasises that adjustment procedures might need to HIV infection in a given time period) was found in two vary between populations. ANC sentinel surveillance studies from Malawi. data are used as input into the Estimation and Projection Pilcher and colleagues found a proportion of 1.8% acute Package (EPP) software of UNAIDS to estimate the (antibody negative) HIV infection among STD and prevalence per location and region. These projections take dermatology clinic attendees, which has high transmission into account the biases associated with over-represented potential because of high viral load and presence of urban ANC sites, but ignore the other biases. STDs.6 We have no recent incidence data of young people to assess changing incidence following health education The estimated average adult (15-49 yrs) prevalence behaviour modification campaigns. in Malawi for 2003 was 14.4% (95% CI: 12%-17%). Prevalence of HIV Estimated prevalence in urban adults (23.0%; 95% CI: Malawi monitors its HIV prevalence (number of HIV 19%-28%) was nearly twice as high as in rural adults infections existing at a certain point in time) through (12.4%; 95% CI 10-15%). The estimated prevalence in sentinel surveillance at antenatal clinics (ANC). The most the South in 2004 was 19.5%, almost double that of the recent ANC sentinel data were collected from February North (11.3%) and Central regions (9.7%) and is projected to April 2003 and resulted in the HIV prevalence rates to stay at that level if HIV prevention programs were to have no impact (figure 1). reported in table 2. Women who visit the antenatal clinic do not represent the general population and thus ANC prevalence data do not represent the prevalence in the general population. When compared with community-based samples, ANC data generally overestimate the prevalence in young women (because ANC women are a selection of sexually active women) and underestimate the risk in older women (because ANC women are a selection of women

Adjusting for the ANC underestimates found in Karonga, the national prevalence of 19.8% found in the ANCs is equivalent to an average national community prevalence of 20.0% and is higher than the NAC estimate of 14.4%. Other sources of HIV prevalence data are clinical research studies, community based surveys and the data of the Malawi AIDS Counselling and Resource Organisation (MACRO). Their results are tabulated and range from 0% Malawi Medical Journal: Special Edition on Burden of Disease in Malawi I

114 The Epidemiology of HIV in Malawi

Table 2. HIV prevalence by ANC site, 2003

Rural Rural Semi-urban Semi-urban Urban Rural Rural Rural Semi-Urban Semi-Urban Semi-Urban Urban Rural Rural Rural Semi-Urban Semi-Urban Semi-Urban Urban Rural

Number sampled 210 193 517 522 846 238 219 153 548 272 500 810 206 205 203 510 510 511 804 1,627

Number HIV + 43 28 84 126 176 16 25 11 99 27 110 137 35 31 47 74 122 168 222 236

Semi-urban

3,890

Urban

Sentinel Site

Locality

Kaporo Health Centre Mbalachanda Health Centre Rumphi District Hospital Nkhata-Bay District Hospital Mzuzu Health Centre Kamboni Health Centre Thonje Health Centre Kasina Health Centre Mchinji District Hospital St. Anne’s Mission Hospital Ntcheu District Hospital Lilongwe Bottom Hospital Gawanani Health Centre Milepa Health centre Mianga Health centre Mangochi District Hospital Mulanje Mission Hospital Nsanje District Hospital Limbe Health Centre Subtotal

Total

% HIV +

(95% CI)

20.5 14.5 16.2 24.1 20.8 6.7 11.4 7.2 18.1 9.9 22.0 16.9 17.0 15.1 23.2 14.5 23.9 32.9 27.6 14.5

(15.2-26.6) (9.9-20.3) (13.2-19.8) (20.6-28.1) (18.1-23.7) (3.9-10.7) (7.5-16.4) (3.6-12.5) (15.0-21.6) (6.6-14.1) (18.5-25.9) (14.4-19.7) (12.1-22.8) (10.5-20.8) (17.5-29.6) (11.6-17.9) (20.3-27.9) (28.9-37.2) (24.6-30.9) (12.8-16.3)

810

20.8

(19.6-22.1)

2,460

535

21.7

(20.1-23.4)

7,977

1,581

19.8

(19.0-20.7)

Source: National AIDS Commission. HIV Sentinel Surveillance Report 2003. ���������������� Lilongwe, 2003.

in pregnant women in the early 1980s to 99% in patient The Malawi National Blood Transfusion Service screens the blood of donors who receive prior advice about when populations. not to give blood. The donors are therefore a highly selected group. Of 10246 donations between January Figure 1. Projected HIV prevalence per region, 1982-2010 and July 2005 342 (3.34%) were HIV positive using a p24 antigen test (personal communication – Dr J Emmanuel, Director of MNBTS). 25. 00%

20. 00%

South

Nor th Centr al

15. 00%

10. 00%

5. 00%

0. 00%

Yea r

Source: Malawi HIV/AIDS estimates 2003. Technical report. Lilongwe, 2004.

Number of people living with HIV/AIDS The EPP software also estimates the absolute number of people living with HIV/AIDS (PLWHA) from the ANC sentinel data (table 3). Although the urban HIV prevalence is double the rural HIV prevalence, in absolute numbers, more than twice as many HIV infected people live in rural areas as compared to cities. Like elsewhere in sub-Saharan Africa, the HIV epidemic has become a ‘women’s epidemic’ in Malawi, with almost 1.4 times as many women as men infected. Combinations of the nineteen sentinel sites reported in table 2 were used to represent the 27 districts and 4 urban centres of Malawi. The resulting estimates of rural and urban prevalence were applied to the population structure to come up with estimates of the current number of HIV-infected Malawi Medical Journal: Special Edition on Burden of Disease in Malawi I

The Epidemiology of HIV in Malawi 115

Table 3. Estimated number of HIV infected persons in Malawi, 2003 Indicator

Number of PLWHA

95% Confidence Interval

Number of infected adults (15-49 yrs)

760,000

(630,000-910,000)

Number of infected adult women (15-49 yrs)

440,000

(370,000-530,000)

Number of infected urban adults (15-49 yrs)

240,000

(200,000-290,000)

Number of infected rural adults (15-49 yrs)

530,000

(440,000-640,000)

Number of infected older people (50 yrs and >)

60,000

(50,000-70,000)

Source: National AIDS Commission. HIV/AIDS in Malawi. 2003 estimates and implications. Lilongwe, 2004.

Table 4. Estimated number of HIV infected persons per district and region District Chitipa Karonga Rumphi Nkhata Bay

Number of PLWHA 7,000 16,000 6,000 10,000

District Mzimba Mzuzu City Likoma

Number of PLWHA 22,000 13,000 1,000

Total Northern Region Kasungu Nkhotakota Ntchisi Dowa Salima

75,000 21,000 10,000 9,000 21,000 24,000

Lilongwe Rural Lilongwe City Mchinji Dedza Ntcheu

Total Central Region Mangochi Machingaw Balaka Zomba Rural Zomba Municipality Chiradzulu Mwanza

29,000 63,000 12,000 16,000 12,000 216,000

54,000 32,000 22,000 41,000 13,000 18,000 12,000

Blantyre Rural Blantyre City Thyolo Mulanje Phalombe Chikwawa Nsanje

Total Southern Region

29,000 99,000 46,000 42,000 17,000 33,000 17,000 475,000

Source: Malawi HIV/AIDS estimates 2003. Technical report. Lilongwe, 2004

individuals per district and urban centre (Table 4)

common symptoms and diseases during follow-up of home based care patients with stage 3 or 4 AIDS disease. Patients most often complained of cough, chest pain and fever, Incidence of AIDS-related diseases A 16 month follow up study of 660 HIV positive and like in the Ndirande study, uncomplicated diarrhoea people in Ndirande reported the incidence of AIDS was the most commonly diagnosed disease, followed by and related diseases prior to the availability of ARVsj. oral candidiasis and uncomplicated malaria. The hospitalisation and death rate by CD4 count and WHO staging at enrolment are found in a copy of their Prevalence of AIDS-related diseases table 5. Note TS is an abbreviation of Trimethoprim- The joint Salvation Army/College of Medicine Bangwe Sulfamethoxazole. The most common event was non- home based care project also assessed the presence of specific diarrhoea (37 events per 100 person-years) symptoms at first assessment, severity and duration. followed by oral candidiasis, uncomplicated malaria, and Headache was the most common presenting symptom, fever of unknown origin. Bacterial disease was common closely followed by fever, chest pain, shortness of breath (16.2 new events per 100 person-years), but the majority and cough. A few studies have reported on specific of bacterial isolates were resistant to TS in vitro. The AIDS related diseases. For TB, please refer to the TB joint Salvation Army/College of Medicine Bangwe home chapter. A study of stroke-like illness in HIV seropositive based care project has also enumerated the incidence of Malawi Medical Journal: Special Edition on Burden of Disease in Malawi I

116 The Epidemiology of HIV in Malawi

Table 5. Incidence of hospitalisation and deaths per 100 person-years of observation by CD4 strata and WHO clinical stage, Ndirande (Ref 10) CD4 Cells/ mm3 350

P

I

II

III

IV

n=289

n=215

n=135

n=21

P

n=125

n=159

n=173

n=175

172 (138-212)

84 (64- 106)

27 (12-39)

90 (11-29)

0.003

15 (3-9)

60 (46-76)

178 (144-217)

237 (142-370)

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