AIDS Care
ISSN: 0954-0121 (Print) 1360-0451 (Online) Journal homepage: http://www.tandfonline.com/loi/caic20
HIV infection and intervention: The first decade E. J. Beck To cite this article: E. J. Beck (1991) HIV infection and intervention: The first decade, AIDS Care, 3:3, 295-302, DOI: 10.1080/09540129108253076 To link to this article: http://dx.doi.org/10.1080/09540129108253076
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AIDS CARE, VOL. 3, NO. 3,1991
295
HIV infection and intervention: the first decade E. J. BECK
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Academic Department of Public Health, St Mary’s Hospital Medical School, London, UK
Introduction
Since the recognition of the Acquired Immunodeficiency Syndrome (AIDS) a decade ago (CDC, 1981a,b), the morbidity and mortality attributable to HIV disease has increased dramatically. The number of AIDS cases reported to WHO at the end of 1990 was 0.4 million (Anonymous, 1991), while the estimated global number of AIDS cases for this period was 1.3 million (Merson, 1991). This is projected to increase to 6 million cases by the year 2000 (Chin et al., 1990). The estimated number of HIV-infected adults up to 1990 was 9 million (Merson, 1991), projected to 18 million HIV-infected adults by the year 2000 (Chin et al., 1990). This paper provides an overview of some of the developments in our understanding of HIV-infection over this last decade. It will review the intervention measures successfully employed against this pandemic to date and will also describe the outline of an integrated intervention strategy. Such an approach needs to be developed to devise specific interventions, appropriate to the social and economic context in which they are required.
HIV transmission The agent associated with AIDS is a retrovirus, Human Immunodeficiency Virus (HIV). Two related, though genetically distinct (Gallo & Nerurkar, 1987), viruses have been identified: HIV-1 and HIV-2 (Barre-Sinoussi et al., 1983; Guyader et al., 1987). Though they have different prevalence patterns (De Cock & Brun-Vezinet, 1989), their transmission characteristics and natural history of infection are similar (De Cock et al., 1990). HIV transmission involves sexual, parenteral and transplacental routes (Mann & Chin, 1988). The sexual route involves both heterosexual and homosexual transmission, while parenteral transmission involves both infected blood/blood products and infected (re-used) needles or syringes. Global regional differences according to transmission characteristics have been described (Sato et al., 1989). Pattern 1, observed in industrialized nations including Western Europe and the US, is characterized by the predominance of homosexual and parenteral transmission, the latter predominantly involving injecting drug users (IDUs). Pattern 2, observed in Subsaharan Africa and the Caribbean is characterized by predominant heterosexAddress for correspondence: Dr E. J. Beck, Academic Department of Public Health, St Mary’s Hospital Medical School, Norfolk Place, London, W2 lPG, UK.
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296 E. J.BECK ual transmission and iatrogenic parenteral transmission through infected blood/blood products or reused needles and syringes. Transplacental transmission is high in this context because of the large number of infected females. A third pattern, pattern 112, is currently observed in Central and South America and constitutes a transitory phase from a predominance of pattern 1 to pattern 2, specifically a switch from predominant homosexual to heterosexual transmission. A similar transition was observed in the Caribbean in the mid1980s and heterosexual transmission is likely to predominate in Central and South America in the near future. Away from the global epicentres of the HIV pandemic, pattern 3 countries are characterized by the heterogeneity of both sexual and parenteral transmission, while the overall prevalence of infection in these countries is currently thought to be relatively low. Again, within some of these pattern 3 countries epicentres of high prevalence are now developing (Kumnuan et al., 1990). The importance of sexual transmission was recognized early within the course of the pandemic, though initially only predominantly within the context of homosexual transmission (Peterman et al., 1985). The increasing importance of heterosexual transmission has received prominence only since the mid-1980s (Editorial, 1986). While it is estimated that in 1985 50% of global transmission was due to heterosexual transmission, this is thought to have increased to 60% in 1990 and estimated to increase to 75% by the year 2000 (Merson, 1991). Though these global patterns provide us with a useful conceptual framework, they are based on prevalence patterns and therefore of limited value. The occurrence and importance of heterosexual transmission is currently well recognized in pattern 1 countries (Padian, 1987; Beck et al., 1989; Anonymous, 1990) and the transition currently observed to be occurring in Central and South America reinforces their limitation. Another transition which has been observed is the shift of burden associated with HIV infection. While 50% of global transmission in 1985 was estimated to occur in Third World countries, this has increased to 65% in 1990 and 80% is anticipated by the year 2000 (Merson, 1991). These transmission changes can be expected to result in a concomitant increase in HIV-disease burden, which is reflected in increased morbidity and mortality. HIV transmission has been associated with the occurrence of other sexually transmitted diseases (STDs) (Pepin et al., 1989). Whether this association is direct, mediated through sexual activity or both is currently being addressed (Mertens et al., 1990). Once an individual is infected, HIV-DNA is incorporated into the host cell DNA. Many cells are targeted, particularly CD4-lymphocytes and macrophages or monocytes. Whereas the cytopathic effect of HIV on the CD4-lymphocytes is thought to result in immunosuppression, infected monocytes and macrophages not only constitute the main reservoir of HIV in infected individuals but also act as a transport mechanism within hosts and between individuals (Rosenberg & Fauci, 1989; Levy, 1989). The latter could explain enhanced transmission of HIV in the presence of other STDs.
HIV disease A period of viral latency is now recognized to occur between time of HIV-infection and the development of HIV-disease. HIV-disease constitutes the symptomatic phase of HIVinfection and covers a spectrum ranging from non-specific manifestation of immunosuppression, like oral candidiasis or non-specific constitutional symptoms (weight losdnight sweats), to specific opportunistic infections or tumours, like Pneumocystis carinii pneumonia and Kaposi’s sarcoma (CDC, 1987). Important questions concerning the natural history of HIV infection which remain unanswered include whether all infected individuals necessarily develop symptomatic disease, for those who progress what the average duration between
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time of infection and developing symptomatic disease is and the general relationship between viral latency and reactivation. As HIV-DNA is incorporated within the DNA of the host cell, each cell is infected for the remainder of its existence. While many infected individuals may eventually develop symptomatic disease (Biggar et al., 1990), evidence is accumulating that this may not always be the case (Farzadegan et al., 1988; Bolognesia, 1989). If substantiated HIV-infection would conform to other infectious diseases where the condition of asymptomatic infected individuals is well recognised (Petersdorf, 1983). This issue is closely related to the incubation period for progression from asymptomatic infection to symptomatic disease. Whereas earlier studies suggested an incubation period of 5 years, current studies point to a median incubation period of around 10 years (Biggar et al., 1990; Rutherford et al., 1990). Whether this increased incubation period is due to less aggressive disease or our increased understanding of the natural history of HIV infection is currently controversial. As viral reactivation appears to be dependent on some extracellular stimulus (Rosenberg & Fauci, 1988), other STDs and long latency viral infection have been postulated as cofactors for disease progression. Whereas the evidence for STDs acting as cofactors is currently contradictory (Weber et al., 1986; Coates et al., 1990), early evidence suggests that long latency viral infection can influence disease progression (Rosenberg & Fauci, 1988; Webster et al., 1989).
Agent, host and environment Any disease process occurs because of the interaction between agent, host and environmental factors (Beck, 1985 and in press). Not only does this model provide us with an analytic framework in which to interpret disease causation, it also provides a framework in which appropriate intervention policies can be devised and evaluated. For the HIV-pandemic, any comprehensive intervention policy needs to address two levels. The first level is centred on HIV-infected individuals and is primarily aimed at minimizing the deleterious effect of HIV-infection or disease. The second level is geared towards breaking HIV-transmission in populations.
Infected individuals To date the best documented intervention for retarding progression from asymptomatic infection to symptomatic disease is the introduction of zidovudine during the latter stage of the asymptomatic phase (Volberding et al., 1990). The importance of cofactors as described above remains controversial. Once symptomatic disease has developed, intervention is aimed at treating the opportunistic infections and tumours caused by the immunosuppression, reversing the immunosuppression and treating the side effects of the therapeutic compounds used. Contemporary antiviral therapy, particularly zidovudine, does not reverse the immunosuppression caused by HIV infection but slows down viral replication (De Clercq, 1991). Since the widespread introduction of zidovudine in 1987, a number of other antiviral agents are currently under investigation. Some of these act early in the course of infection, preventing viral entry or transcription while others act during viral replication (De Clercq, 1991). While zidovudine has proved successful (Fischl et al., 1987), its limitations (Dournon et al., 1988) suggest that future anti-viral treatment will probably involve combination therapy (De Clercq, 1991; Johnson & Hirsch, 1990). Morbidity and mortality patterns for people with HIV disease have changed during the
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second half of the decade. The median two year survival time has doubled from 10 months prior to 1987 to 20 months since then, a phenomenon not only observed in the UK (Peters et al., 1991) but also the US, Denmark and Australia (Rothenberg et al., 1987; Pedersen et al., 1990; Solomon, 1990). These improvements have been primarily linked to a reduction in mortality associated with pneumocystis pneumonia (Peters et al., 1991; Harris, 1990; Lemp et al., 1990). The reduced case fatality is probably due to a number of reasons, including earlier patient presentation (Beck et al., 1991), increased diagnostic and therapeutic skills (Bennett et al., 1989) and the effect of therapy including zidovudine (Fischl et al., 1987; Peters et al., 1990). Conversely, while the mortality associated with symptomatic disease has improved this has resulted in an increase in associated morbidity. Not only have the number of episodes of Pneumocystis pneumonia increased for individual patients, those AIDS patients who survive longer develop more intractable opportunistic infections, like cytomegaloviral disease (Peters et d.,in press) and tumours like visceral Kaposi’s sarcomas and non-Hodgkin lymphomas (Peters et al., 1991). While the increased use of prophylactic compounds against Pneumocystis (Fisch et al., 1988) may reduce future number of episodes of pneumocystis per patient, the more intractable opportunistic infections and tumours are currently less amenable to therapeutic intervention. The increased use of specific therapeutic agents may itself give rise to significant morbidity. Side effects (De Clercq, 1991; Richman et al., 1987) may require intervention, like repeat blood transfusion for anaemic patients, adding to increased demands on health service resources.
Breaking transmission in populations This requires a multidisciplinary approach which can be categorized in terms of agent, host and environmental factors. The development of an effective HIV-vaccine has long been sought since the recognition of the HIV-pandemic. Because of the mutation rates of these viruses (Rosenberg & Fauci, 1989; Levy, 1989), progress on its development has to date been limited, though current prospects seem more optimistic (Green, 1991). It will, however, be some time before an effective vaccine will become available for mass immunization (Brown, 1991). As HIV infection is associated with other STDs current evidence suggests that HIV containment strategies need to be promoted in conjunction with the development of containment programmes for other STDs (Pepin et al., 1989). While genotypic host features are currently not thought to be important, the cultural characteristics of the host are. The social, economic and psychological forces acting on and within individuals influence their attitudinal and behavioural characteristics, and thus influence the extent to which individuals are willing and able to adopt ‘safer sex’ and ‘safer shooting’ principles. That attitudinal changes have occurred subsequent to the various media campaigns has been demonstrated (Beck et al., 1990; DHHS, 1987). In certain circumstances this has resulted in behavioural changes (Weller et al., 1984) though these changes have not occurred universally (French et al., 1990). The economic condition which operate on the host will influence whether individuals can actually implement some of these attitudinal changes. Those individuals wanting to adopt particular behavioural changes will require access to condoms to practice ‘safer sex’ or sterile needledsyringes to implement ‘safer shooting’ principles. Individuals in need of further professional advice on HIV infection will require access to centres where they can go for counselling or testing. To ensure supplies of noninfected blood/blood products all donations will need to be carefully screened by blood
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banks before used to produce particular blood products. Thus, publicly sanctioned provisions of these resources are part of the environmental context enabling individuals to take appropriate measures. While the industrialized nations are pressed to adequately meet these requirements, Third World countries are struggling to meet many of them.
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Mass media Accurate information on HIV infection and possible intervention measures underpin the effective use of these resources. During the mid-1980s a number of media campaigns were undertaken to provide the public with some of this information. While mass campaigns have been successful in putting HIV-infection on the public’s health agenda (Beck et al., 1990) targeted follow-up campaigns will need to continue. The nature of these campaigns will need to be clearly defined. Due to the element of fear associated with some of the earlier campaigns (IPPF, 1988; Morgan, 1987), a significant level of public anxiety was created in the UK (Wellings, 1988). While this anxiety has partly translated itself into an increased public awareness of the problem it has also resulted in the reappearance of a mistaken complacency, especially among heterosexuals in Britain (French ef al., 1990; Coleman, 1988). A major aim of any educational campaign is to raise sufficient awareness to motivate individuals and groups to incorporate its message and to make appropriate behavioural changes. This should, however, occur without raising anxiety levels to the extent that a public scarce or panic is created. Government departments, the popular press and television all exert enormous influence on public opinion (Wellings, 1988) and therefore need to share the responsibility to determine the appropriate nature and intensity of future campaigns. The relationship between the ‘general’ public and those groups most severely affected during the first decade of the epidemic needs constant evaluation. To further marginalize HIV-infected individuals and the groups to which they belong not only raises serious humanitarian issues but will severely limit effective intervention strategies (Muir, 1990; Cohen & Faragher, 1991). Public attitudes towards sex and sexuality, drug use and racial discrimination are but some issues which set the moral background, in which these strategies need to be implemented. Resources
It will require the ongoing provision of resources in order to establish, run and accommodate the necessary services in line with the changing nature of the epidemic. While health care systems in many industrialized societies are currently groaning under the yolk of costcontainment (Beck & Adam, 1990), the increasing caseload in conjunction with prolonged survival will place increasing resource demands on both therapeutic and preventive services. While many industrialized nations are finding it hard to meet these demands the situation in the Third World has become progressively worse over the last decade. The anticipated increase in disease burden will exacerbate an already precarious situation, and provides another impetus to solve the problem of Third World debt (Rodgers, 1991). It has already been stated that a major irony of the HIV pandemic is that it highlights old problems in a new format (Beck et al., 1989). In the first decade of the HIV pandemic we have learnt a lot about the natural history of HIV infection, raising new questions while some pertinent old ones have remained unanswered. Awareness concerning the seriousness of this public health problem has been raised while we have scored modest successes in terms of ameliorating some of the consequences of this pandemic. Successful intervention can occur for those infected with
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HIV, increasing the period of asymptomatic infection and improving survival with HIV disease. Similarly, viral transmission can be interrupted but only through a comprehensive strategy addressing agent, host and environmental factors in a complementary fashion. Such policy implementation will require ongoing multidisciplinary research and policy evaluation. While we have successfully addressed some of the earlier challenges of the HIV pandemic, if we have the political will to develop appropriate containment strategies, some of the challenges which will face us in the second decade of the HIV pandemic may even be more formidable than during the first.
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