The growing challenge of HIV/AIDS in
developing countries
Alison D Grant* and Kevin M De Cock**
'London School of Hygiene and Tropical Medicine, London, UK and fDivision of HIV/AIDS
Prevention - Surveillance and Epidemiology, Centers for Disease Control and Prevention, Atlanta,
Georgia, USA
The burden of HIV infection and disease continues to increase in many
developing countries. An emerging theme is of an HIV pandemic composed of
mini-epidemics, each with its own characteristics in terms of the trends in HIV
prevalence, those affected, and the HIV-related opportunistic diseases observed.
A number of explanations for the observed differences in the spread of HIV
infection have been proposed but since the factors concerned, such as sexual
behaviour and the prevalence of other sexually transmitted diseases, are closely
interrelated, it is difficult to tease out which are the most important. Among
HIV-related opportunistic diseases, tuberculosis stands out as the most important
cause of morbidity and mortality in most developing countries, but the relative
prevalence of other diseases shows considerable regional variation. Thus, there
is a need for local approaches to the global problem of managing HIV disease.
The most pressing public health challenges are to use existing knowledge of
strategies to reduce HIV transmission, and to apply them in ways appropriate to
the local situation, and to develop, evaluate and implement interventions to
prolong healthy life in those already infected.
Correspondence to
Dr Alison Grant
Infectious Diseases
Epidemiology Unit
Department of Infectious
and Tropical Diseases,
London School of
Hygiene and Tropical
Medicine, Keppel Street
London WC1E 7HT, UK
The human immunodeficiency virus (HIV) pandemic has emerged, over
the 16 years since the first description of a cluster of cases of Pneumocystis carinii pneumonia (PCP) among homosexual men in Los Angeles1,
to become one of the most important global public health challenges of
recent times. Since the start of the epidemic, issues around HTV and the
acquired immunodeficiency syndrome (AIDS) have had a high profile in
industrialised countries. However, the burden of disease continues to fall
most heavily, and often less visibly, in developing countries, particularly
in Africa. In industrialised countries, the recent introduction of highly
active antiretroviral therapy has raised hopes of substantially improved
prognosis for HTV-infected individuals. By contrast, in developing
countries, very little has happened to improve the gloomy outlook,
particularly for those with symptomatic disease who have reached the
stage of severe immunosuppression.
British Medical Bulletin 1998;54 (No. 2) 369-381
C The British Council 1998
Tropical medicine: achievements and prospects
In this article, we review the current global situation of the HTV/AIDS
pandemic, highlighting the regional differences in epidemiology that are
becoming apparent, exploring possible reasons for this heterogeneity
and outlining the challenges that HTV7AIDS presents to pubhc health in
the developing world.
The current situation
Burden of HIV infection
The World Health Organization (WHO) estimated that, at the end of
1997, 30.6 million people worldwide were living with HTV/AIDS, of
whom over 90% were in developing countries, two-thirds in subSaharan Africa2. An emerging theme in the global epidemiology of HIV
is of regional variation; thus the global pandemic is composed of
different regional or local epidemics, each with its own characteristics3-4.
For example, within the countries of sub-Saharan Africa, there are
substantial differences in the observed trends in HTV prevalence. These
are most often compared using data from pregnant women, despite
potential difficulties in assuming that HTV prevalence in pregnant
women is representative of that in the general population5.
Trends in HTV prevalence in selected countries in sub-Saharan Africa
are illustrated in Figure 1. In some central and west African cities, such
as Kinshasa and Yaounde, HTV prevalence seems to have remained
stable at relatively low levels. By contrast, in other countries,
particularly in eastern and southern Africa, there has been an explosive
rise in prevalence to much higher levels. These differences cannot be
Fig. 1 Trends in HIV
prevalence among
pregnant women in
selected cities in subSaharan Africa.
Adapted from Buv6 et
a/1 with additional
data from the US
Bureau of the
Census".
370
1985
1986
1987 1988 1989 1990 1991 1992 1993 1994
«-Kampala -"-Lusaka -*-Kinshasa
-*-Abidjan -*-Yaound6 -x-Francistown
1995
1996
British Medical Bulletin 1998;54 (No. 2)
HIV/AIDS in developing countries
accounted for simply by differences in the duration of the epidemic. For
example, the first AIDS cases in Kinshasa, Lusaka and Kampala were all
observed in 1983; HIV prevalence has increased dramatically in Lusaka
and Kampala, but not in Kinshasa6.
There are some encouraging data which suggest that the situation may
be improving in some countries. Declining HIV prevalence has been
reported in a rural population cohort in Uganda7, and among military
recruits in Thailand8, both of which have been attributed to changes in
sexual behaviour. However, an alternative explanation for the falling
prevalence in Uganda is maturing of the epidemic, with falling
prevalence accounted for by high mortality in the presence of stable and
high incidence9. Stabilisation or decrease in HTV prevalence is far from
universal. Over the same time period, rapid increases in HTV prevalence
have been observed in India, Vietnam, Myanmar (Burma) and South
Africa2-10, and it is predicted that South Africa will experience one of the
worst HTV epidemics in Africa11.
Burden of HIV-related disease
Estimates of the cumulative numbers of AIDS cases point to the burden
of disease falling most heavily in developing countries, particularly subSaharan Africa, which is thought to have accounted for 5 million of the
cumulative total of 6.7 million AIDS cases from the late 1970s to the
end of 199612. In other developing countries, particularly those in Asia,
the epidemic started later and so the burden of AIDS cases may be
expected to increase sharply over the next few years. In some countries
where the epidemic is well established, HTV infection is the leading cause
of death among adults1314.
Spectrum of disease: causes of morbidity and mortality
In industrialised countries, the spectrum of HIV-related disease is well
described: in the US and Europe, the most frequent AIDS-defining
disorders are PCP, Kaposi's sarcoma and oesophageal candidiasis15'16.
There are far fewer data from developing countries, largely because of
lack of access to the necessary diagnostic facilities.
In Table 1, the relative frequencies of HIV-related opportunistic
infections among hospitalised patients in Africa, South America and
Asia are compared. It is difficult to make direct comparison between
these studies because of differences in methodology. In the two studies
from Africa, patients admitted to hospital were recruited systematically,
regardless of HTV status or clinical presentation. In the other studies,
British Medical Bulletin-\998;5* {No. 2)
371
Tropical medicine: achievements and prospects
Table 1 Spectrum of opportunistic disease in HIV-infected adults in different regions
Region
Sub-Saharan Africa
Latin America
South & southeast Asia
Country
Reference No.
C6te d'lvoire
Grant
(Unpublished)
Kenya
17-19
Brazil
20
India
22
Hospitalized
HIV*
patients'
HIV*
medical
ward
admissions
No HIV* patients
349
95
111
107
100
307
Tuberculosis (%)
Bacteraemia (%)
HIV wasting (%)
Meningitis (%)
Isosporiasis (%)
Bacterial pneumonia (%)
Cerebral toxoplasmosis (%)
Bacterial enteritis (%)
Non-specific diarrhoea (%)
Oesophageal candidiasis (%)
Cryptococcosis (%)
Kaposi's sarcoma (%)
Cytomegalovirus (%)
PCP
Cryptosporidlosis (%)
Penicilhosis (%)
28
18
11
10
7
6
6
5
5
3
2
1
0
0
0
0
18
26
32
-
30"
-
61
-
31
13C
-
5
5
-
-"
1
Population
6
16*
15
1
2
-
Thailand
23
Hospitalised Hospitalised
Patients
Patients
patients
with AIDS, with AIDS
patients
with AIDS
specialist
(sexually
with AIDS
clinic
transmitted)
-
Mexico
21
8
16
14
6
24
5
5
5h
22
8
-
8*
12
47
22
25
-
8«
1
16
-
T
4
24
1
<1
13
5
16
'Patients a d m i t t e d t o infectious diseases and respiratory wards; b m y c o b a c t e n u m ' ; 'salmonellosis (nont y p h i ) ; d t o t a l meningitis n o t listed, but 2 4 % o f all patients had cryptococcal meningitis (listed as
cryptococcosis); ' a c u t e cough and fever' - 4 6 % of this subgroup had pneumococci isolated f r o m blood
culture; 'site of toxoplasmosis not specified; ' p a r a s i t i c diarrhoea'; h ' C M V chorioretinitis'.
— indicates data not available. Patients could have more t h a n one diagnosis.
only patients classified as having AIDS were included and, hence, severe
illness in HIV-infected patients who did not fulfil the ADDS case
definition would have been underestimated. In some studies, only
diseases classified as HIV-related were enumerated: in particular, blood
cultures were performed systematically in both African studies, and in
most patients in the Thai study, but not in the others. This is the most
likely explanation for the high prevalence of bacteraemia in the African
and Thai studies and its absence in the others. In Table 2, data from
three autopsy studies from Cote d'lvoire, Zaire and Mexico are
compared. Again, caveats are necessary when making comparisons: the
study from Cote d'lvoire includes all HTV-infected patients regardless of
their clinical presentations, whereas the other two include only patients
with a clinical diagnosis of AIDS. In addition, there may be differences
372
British Medical Bulletin 1998;54 (No. 2)
HIV/AIDS in developing countries
Table 2 Prevalence of opportunistic diseases identified at autopsy of HlV-infected adults in
different developing countries
Region
Country
Reference No.
Population
No. HIV* patients
Tuberculosis (%)
Bacterial pneumonia (%)
Cytomegalovirus (%)
Bacteraemia (%)
Cerebral toxoplasmosis (%)
Non-specific enteritis (%)
Kaposi's sarcoma (%)
Nocardiosis (%)
Cryptococcosis (%)
Atypical mycobactenosis (%)
PCP(%)
Cryptosporidiosis (%)
Non-Hodgkln's lymphoma (%)
Histoplasmosis (%)
Candidiasis (%)
Sub-Saharan Africa
Cote d'lvoire
Zaire
24
25
HIV patients
Patients with
dying in
AIDS dying
hospital
in hospital
Latin America
Mexico
26
Patients with
AIDS dying
in hospital
247
63
177
38
30
18
16
15
10
9
4
3
3
3
3
3
2
41*
34
13
-
25b
11
69<
-
11 d
16
-
17
30
1
11
6
24
7
5
10
5«
-
19*
<2
<2
<2
31'
1
Mycobacterial disease, extrapulmonary, probably Mytobacterium
tuberculosis';bdisseminated
d
tuberculosis;'cytomegalovirus infection, disease not specified; brain only available in one case - 10%
disseminated toxoplasmosis, 1 % cerebral; • cry ptococcoses, extrapulmonan/; 'candidiasis, esophagus or
trachea';'oral and oesophageal candidiasis, and fungal pneumonia.
in the definition of specific diseases, particularly with respect to cytomegalovirus and candidiasis.
Despite the difficulties in making comparisons, it is striking that in
almost every study from developing regions, tuberculosis is the most
frequently identified opportunistic disease. There are marked variations
in the prevalence of other diseases usually regarded as HTV-associated.
This may be due partly to differences in ascertainment, but data from
other studies support the idea that there are important regional
variations in HTV-related diseases; for example PCP, which is relatively
common in Central and South America20"21 •2<s and in Thailand n, but rare
in most African countries27. The implications are that tuberculosis
control is a major priority in limiting the effects of HTV on public health
in developing countries in all regions, but that differences in the relative
prevalences of other opportunistic diseases mean that guidelines for
appropriate presumptive treatment and prophylaxis for HTV-infected
individuals should be region-specific28.
British Medical Bulletin 1998,54 (No. 2)
373
Tropical medicine: achievements and prospects
Reasons for heterogeneity of the epidemic
Proposed explanations for regional variations in the HTV epidemic may
be divided into factors which may influence HIV prevalence and those
which may influence the clinical manifestations of HTV disease.
Heterogeneity in HIV prevalence
Virus factors There are striking differences in the epidemiology of the
two types of human immunodeficiency virus: HTV-1 has caused a global
epidemic, whereas HTV-2 has remained largely confined to west Africa,
where its prevalence is stable or declining29. It is therefore plausible that
differences between the subtypes of HTV-1 may contribute to regional
differences in epidemiology. In Thailand, a case-control study suggested
that there might be increased heterosexual transmission of subtype E
compared with subtype B30, although it was not possible to control for
the effect of the mode of HTV acquisition (sexual or intravenous drug
use)31. Subtype A is predominant in all parts of sub-Saharan Africa
except for South Africa and Malawi32, and so differences in subtype
alone cannot account for the marked differences in HTV prevalence
observed in African countries.
Host factors Host factors are generally thought to be the most
important determinants of global differences in the epidemiology of HTV
infection. These can be divided into, first, factors that influence the risk
of exposure to HTV, such as patterns of sexual mixing, the extent of
concurrent sexual partnerships and rate of partner change; and second,
factors which influence the risk of transmission of HTV during contact
with an infected individual, including sexual practices, the prevalence of
other sexually transmitted diseases, circumcision, condom use, and the
stage of HTV disease of the infected individual6.
Existing data demonstrate regional differences in some of these
factors, but their relative importance is difficult to determine, not least
because many of them are interrelated, such as sexual behaviour and the
prevalence of sexually transmitted diseases. A multicentre study to
explore the role of differences in sexual behaviour, the prevalence of
sexually transmitted diseases and circumcision in determining
differential spread of HTV infection in Africa is currently in progress:
this is a collaborative project between the Institute of Tropical Medicine
in Antwerp, the London School of Hygiene and Tropical Medicine
(LSHTM), INSERM and UNAIDS.
In addition, studies of individuals who remain seronegative despite
being highly exposed to HTV suggest that there may be biological factors
374
British Medical Bulletin 1998,54 (No. 2)
HIV/AIDS in developing countries
which confer protection against infection ('natural immunity') although
the mechanism for this phenomenon is unclear33.
Environmental factors Environmental factors which may influence the
spread of HIV infection include societal factors such as socio-economic
status, urbanisation and migration, the stage of the HIV epidemic in the
population (since this may affect infectiousness), differences in duration
of survival with HIV infection (since the prevalence of a disease is
related to its duration) and societal responses to the epidemic34.
Migrant populations are particularly vulnerable to HTV infection. In
West Africa, the migration of agricultural workers to all-male camps,
where many men share the services of a small number of female
prostitutes, results in a pattern of sexual mixing which promotes the
spread of HIV infection35. Women also migrate in search of
employment, for example Ghanaian women to neighbouring Cote
d'lvoire, where many work as prostitutes35. Cote d'lvoire is the major
destination for migrant workers in West Africa, and this may be one of
the reasons why it has the highest HTV prevalence in the region36. The
observed trends in HTV prevalence in Abidjan are consistent with
migration being an important contributor to the epidemic: the
male:female ratio of AIDS cases was 4.8:1 in 1988, but had fallen to
1.9:1 by 1993, consistent with the early epidemic being concentrated
among a core group of female sex workers and their male clients37.
HTV and developmental issues are also closely linked. The highest HTV
prevalences are seen among those who are poor, marginalised or
displaced, and the most likely consequence of the HTV epidemic in
developing countries is to increase the gap between rich and poor38.
Heterogeneity in spectrum of disease
Environmental factors Environmental factors are likely to be the most
important determinants of regional differences in the prevalence of HTVrelated diseases. The majority of adults in developing countries are
infected with tuberculosis, and the development of HTV infection
provides the strongest known risk factor for the development of
tuberculosis disease39-40. It is, therefore, not surprising that tuberculosis
is the most common HTV-related disease in most developing countries,
but is less prevalent in industrialised countries where infection with
tuberculosis is less widespread.
In African countries, bacterial infections are the second major cause of
HTV-related disease27. The high prevalence of disease due to enteric
pathogens such as non-typhoid salmonellosis is probably attributable to
the overcrowded, insanitary living conditions associated with poverty in
British Medical Bulletin 1998;54 (No. 2)
375
Tropical medicine: achievements and prospects
many developing countries41. HTV-related diseases caused by pathogens
which have a restricted global distribution, such as Penicilliunt
marneffei in southeast Asia, are confined to HTV-infected individuals in
those regions.
The regional differences in the prevalence of PCP are harder to
understand. As shown in Tables 1 and 2, PCP is a common HTV-related
illness in those countries in Latin America, India and southeast Asia
where appropriate studies have been carried out. In Africa, PCP has
been identified in HTV-infected adults and children in autopsy studies24-42
and in adults with respiratory disease43"*8. However, it is less important
as a respiratory pathogen than tuberculosis and bacterial infections48"51.
In a study from Abidjan, Cote d'lvoire, most HTV-infected adults
hospitalised with respiratory disease had CD4 counts below 200 x
106/l51. It is, therefore, unlikely that the reason for the lack of PCP in
African populations is because patients die of other diseases before they
reach the level of advanced immunosuppression at which PCP occurs.
Host factors Host factors may influence the expression of some HTVrelated diseases. For example, Kaposi's sarcoma-associated herpes virus
(HHV-8) has been identified from a high proportion of Kaposi's sarcoma
lesions in a number of populations52. The seroprevalence of HHV-8
among HTV-negative persons who do not have Kaposi's sarcoma is much
higher in Uganda than in North America53. It remains to be determined
whether the association between HHV-8 and Kaposi's sarcoma is causal,
and if so what factors determine whether Kaposi's sarcoma develops in
HHV-8-infected individuals. Among heterosexual populations, the higher
prevalence of Kaposi's sarcoma in men than women suggests a hormonal
influence on susceptibility to tumour development54.
An individual's HIV transmission category may also influence
susceptibility to opportunistic disease. Among HFV-infected individuals
in Thailand, intravenous drug users were more likely to have
tuberculosis and bacterial infections, and less likely to have cryptococcal
meningitis and PCP compared with those who were infected by sexual
transmission55.
Public health challenges
Prevention of HIV infection
The great majority of HIV infections worldwide are heterosexually
transmitted, and a number of strategies have already been shown to be
effective in reducing sexual transmission. For example, at the individual
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HIV/AIDS in developing countries
level, consistent condom use reduced transmission between HIVdiscordant couples56; at the community level, improved management of
sexually transmitted diseases reduced HTV incidence57; and at the
national level, campaigns in Thailand promoting condom use seem to
have been effective in changing sexual behaviour and reducing HTV
incidence8. Successful programmes to prevent sexual transmission need
to integrate condom promotion, behaviour change and control of
sexually transmitted diseases: other important strategies include the
provision of voluntary counselling and testing services, youth
interventions and education for girls. The main priority in reducing the
sexual transmission of HTV is to ensure that strategies of proven
effectiveness are applied in a way appropriate to the local situation.
As more women become infected with HIV, mother-to-child
transmission becomes an increasingly important problem. The
ACTG076 trial showed that mother-to-child transmission can be
reduced using a complex regime of zidovudine58. The zidovudine regime
as used in this trial is neither feasible nor affordable for most women in
developing countries, and trials are underway to evaluate the efficacy of
more practical regimes. Breast feeding has been shown to confer an
additional risk of HTV transmission to children who are uninfected at
birth59 but, in populations that have difficulty in preparing formula feed
safely, the relative risks and benefits of early weaning need to be
investigated.
In industrialised countries, strategies to reduce HIV transmission by
blood transfusion have been highly effective, and less than 0.1% of
infections are transmitted by this route60. However, the same success has
not been achieved in all regions: in many African countries, about 10%
of new HTV infections are attributable to blood transfusion60. Reduction
of HTV transmission by this route requires that blood is transfused only
when it is essential to save life; that blood is donated by unpaid,
altruistic volunteers, with exclusion of potential donors at high risk of
recent HIV infection; and that donated blood is screened for HTV
antibodies using a test with high sensitivity60.
Mitigation of HIV disease
Most public health strategies in developing countries to date have
justifiably focussed on prevention of HIV transmission. However, the
increasing burden of HIV disease in many countries cannot be ignored.
There is a continuing lack of basic epidemiological data concerning the
relative prevalences of opportunistic infections in many regions, for
example southern Africa, and without such data it is difficult to develop
appropriate strategies for the management and prevention of HW-related
British Medical Bulletin 1998;54 (No. 2)
377
Tropical medicine: achievements and prospects
disease. It is clear, however, that tuberculosis is the major cause of HTVrelated disease in the majority of developing countries, and improving
the control of tuberculosis is vital to protect the health of both HTVinfected and uninfected individuals.
Management of other HTV-related diseases in resource-poor settings is
made difficult by the lack of laboratory facilities, without which precise
diagnosis is often impossible, and the prohibitive cost of treatment of
many opportunistic infections. Clinical algorithms for diagnosis and
management of the opportunistic diseases most prevalent in a particular
region need to be developed and tested, and essential drugs lists
implemented. Prophylactic regimes aimed at preventing the most common
opportunistic infections in a particular region need to be evaluated.
The use of antiretroviral treatments in developing countries is an issue
which is increasingly pressing. The dramatic short-term benefits of
highly active antiretroviral therapy seen in industrialised countries draw
attention to their unavailability to the majority of people in countries
where the burden of HTV disease is heaviest. In reality, the newer
antiretrovirals are already available to a privileged minority in many
resource-poor countries, and there is concern that incorrect use of these
treatments could lead to the development of resistance, rendering the
drugs useless. Discussion of these difficult issues needs to continue with
the aim of reversing the trend of increasing inequality between rich and
poor countries in access to effective treatment.
Research priorities
Priorities for research on HTV prevention in developing countries
include evaluation of female-controlled methods to prevent sexual
transmission of HIV, such as vaginal microbicides, developing practical
strategies to improve the control of sexually transmitted diseases, and
developing and evaluating programmes to promote sexual health among
adolescents; evaluation of feasible antiretroviral regimes to reduce
mother-to-child transmission in developing countries; and examining the
relative risks and benefits of breast feeding in different situations.
Priorities for the mitigation of HTV disease include defining the
spectrum of HTV-related disease in different regions; developing and
evaluating clinical algorithms for diagnosis and management of
common HTV-related conditions, and primary prophylactic regimes
directed against the most prevalent opportunistic infections in specific
regions; and working towards effective and sustainable use of
antiretroviral therapy in resource-poor countries.
Perhaps the greatest challenge is to avoid becoming discouraged in the
face of a problem which may seem overwhelming. To quote someone
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British Medical Bulletin 1998;54 (No. 2)
HIV/AIDS in developing countries
living with HIV/AIDS, on the subject of access to antiretroviral
treatments: This is not an overnight process. Let us build slowly. Each
day and each month, more people will have access to antiretrovirals. Let
us take it a step at a time, a day at a time - the way I live my life61.
Acknowledgments
ADG was an MRC Training Fellow. Additional funding for work in
Abidjan was received from the Roche African Research Foundation and
the Rockefeller Foundation.
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