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AIDS Care: Psychological and Sociomedical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
Natural history of HIV and AIDS C. A. Lee
a
a
Consultant Haematologist, Katherine Dormandy Haemophilia Centre and Haemostasis Unit , Royal Free Hospital , London, UK Published online: 25 Sep 2007.
To cite this article: C. A. Lee (1990) Natural history of HIV and AIDS, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 2:4, 353-357, DOI: 10.1080/09540129008257752 To link to this article: http://dx.doi.org/10.1080/09540129008257752
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
AIDS CARE,VOL. 2, NO.4, 1990
353
Natural history of HIV and AIDS
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
C. A. LEE Consultant Haematologist, Katherine D m a n d y Haemophilia Centre and Haemostasis Unit, Royal Free Hospital, Londg UK
Introduction This conference has reported updates of previously well-documented cohorts of homosexuals and haemophiliacs. A new development has been the reports of progression in intravenous drug users (IVDU) and African women. There has been an explosion in sero-prevalence data with two new areas of concern: Eastern Europe and India. Many workers have reported on the influence of treatment on progression rates, and there has been a great effort to establish surrogate markers which may measure the effect of treatment. The disease was set in context at an Introductory Seminar ‘Comprehensive Management of HIV Disease’ during which Ressler spoke on natural history. He pointed out that in the US, AIDS incidence had levelled off and there was a delay in the progression from asymptomatics to CDC IV. This was in part secondary to anti-viral treatment and anti-pneumocystis (pcp) primary prophylaxis. Progression rates in the most reliable San Francisco cohort were 50% at 10 years, and the CD4 count remained the best surrogate market. H N disease should be considered as a ‘chronic ongoing viral disease’ and similar to many other chronic medical conditions, e.g. diabetes and hypertension. Hessol reported on the San Francisco cohort (ThC33). This is a group of 359 men who were amongst 6705 studied during 1977-80 as part of a mal of hepatitis B
vaccine. There was a first anti-HIV positive serum in 135 of these men. These patients have been subject to annual clinical review. Since 1986 regular T subsets have been measured and the clinical outcome (asymptomatic; ARC-candida, leukoplakia, weight loss and fever, or AIDS) monitored. Depending on the year of seroconversion 1977-80, 1981-83, 1984-86 and 1986, the percentage of patients developing AIDS is 61%, 42%, 29% and 0%. The Kaplan-Meier estimate of progression was 49% at 10 years, and 53% at 11.1 years. The actual progression in this cohort diverges from the modelled progression, suggesting an influence of treatment. Forty-five per cent of the cohort are now receiving zidovudine and 43% aerolized pentamidine. It is however difficult to discern the precise effect of treatment from other factors. Pedersen (ThC34) gave an update of 162 anti-HIV positive Danish .patients in many of whom details of the original seroconversion illness was known. These patients had a known date of seroconversion defined as the mid-point between the last negative and first positive anti-HIV. The great majority were male homosexuals. The progression end-points were recurrence of p24, CD4 less than 200/ul, and development of AIDS. Five years from seroconversion 50% had progressed to a CD4 count less than 200/ul and 22% had progressed to AIDS. Amongst those who had endured a
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
354
SAN FRANCISCO SUMhiARIEs. C A. LEE
more severe, protracted seroconversion illness at 5 years, 65% progressed to immunodepression and 38% to AIDS. In contrast, those with less severe symptoms at seroconversion, at 5 years 36% progressed to immunodepression, and 6.5% progressed to AIDS. The MACS (Multicenter AIDS Cohort Study) was reported by Visscher (ThC35). This has 5000 participants and of those 1809 seropositive at entry, 518 (27.4%) have AIDS. The incidence of AIDS per 100 persons per 6 months is 4.2%. This incidence has levelled off since the second half of 1986. Clearly treatment has contributed to this levelling off in the incidence of AIDS. However, since treatment was not in use until the second half of 1987, other factors may have contributed to this slowing of progression. Progression in a cohort of IVDUs by Rainer (ThC36) determined the effects of cessation of drug use. Three hundred and fifty five IVDUs were recruited in 1984, and they did not receive anti-viral therapy. Progression to AIDS was considered in three groups: patients on methadone maintenance, persistent IVDU, and former IVDU. Progression to AIDS and symptomatic disease was much faster in those continuing to inject drugs. As Anzala (ThC37) pointed out, there has been little data on progression in women or African people. A cohort of Nairobi prostitutes was described, which had been established in 1985-90. There were 1,200 women, and in a selected group of 184 followed at 6 monthly intervals who were initially seronegative, 163 seroconverted. The median time taken to progress from asymptomatic to advanced disease was 36 months, and the median time to progress to AIDS was 44 months. There was no correlation with the length of time of prostitution, contraceptive use or pregnancy. There was some correlation with condom use. It is not clear why the progression to symptomatic disease and AIDS should be so rapid in African women. A national cohort of haemophiliacs was
presented by Schinaia (ThC38). This is a multicentre study with 499 participants. Patients were stratified into three groups: age (13 years, 13-34 years. >34 years; type of haemophilia A or B; zidovudine treatment, or no treatment. For the whole cohort, the 5 year progression was 15% and patients aged >34 years had faster progression rates. In contrast the type of haemophilia and zidovudine treatment had no effect on progression rates. Ragni (ThC642) provided a0 update on a cohort of haemophiliacs from Pennsylvania. These haemophiliacs seroconverted between 1978 and 1986. The progression to AIDS was 42%, and to CDC IV alone 11%. PCP had occurred in 4096, but whereas prior to 1989 it had occurred in 52% of AIDS diagnoses, since 1989 it occurred in only 10%. Furthermore, the survival time of haemophiliacs with AIDS who were treated with zidovudine and pentamidine was almost twice that of those diagnosed with AIDS in the pre-treatment era. Lee (ThC641) provided a 10-year follow-up of a cohort of 111 haemophiliacs from the Haemophilia Centre, Royal Free Hospital, London. These patients seroconverted between October 1979 and July 1985. For the 63 patients for whom there was a precise date of seroconversion, the 10 year progression rate of AIDS was 52% (Cl, 34, 70) and to symptoms 87% (C1 75, 99). The median survival time of patients with AIDS was 15 months (range 0-36 months). The therapeutic interventions which could have influenced progression and survival were: prescription of zidovudme since August 1987, secondary prophylaxis with pentamidine since March 1988, and primary prophylaxis with pentamidine since February 1989. This had resulted in improved 18 month survival for AIDS: 33% (C1 6, 59) before August 1987, and 49% (C1 21, 77) since August 1987, Two female partners had become anti-HIV positive and 13 babies (all anti-HIV negative) had been conceived at the time the father was anti-HIV positive. Royce (ThC39) reported on the effect
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
NATURAL HISTORY OF HIV AND AIDS
of cigarette smoking and progression to AIDS. Smoking increases the CD4 lymphocyte count independently of HIV infection. Three hundred and eighty six seropositive men were studied and amongst non-smokers the progression rates to thrush, AIDS and deaths were respectively 39%, 27%, and 12%. Amongst smokers the respective rates were 50%, 33%, and 15%. Even when CD4 was controlled the rates were s t i l l higher in smokers. The reason for this risk factor is not known, although there was some correlation between the number of sexual partners and smoking. Lange (FB81) reviewed the surrogate markers that could be used to measure the effect of anti-viral therapy on clinical progression. The decline in p24 shows the antiviral effect, but can only be used in a subset of data. Zidovudine produces a reduction in plasma viraemia, but this is technically a cumbersome method. Although the pcr technique can be used to assess anti-viral therapy, problems of quantitation are not solved. Zidovudine produces a decline in the B2 microglobulin level. It is possible that the type of biological variant of HIV may have prognostic sigruficance. Viral drug sensitivity or resistance is a problem of increasing concern: 16 or 18 patients showed mutations of codon 215 after 2 years treatment. Jacobson (FB82) reported on the important use of serum markers as candidate surrogate markers for the effect of antiretroviral therapy in delaying progression. Ninety patients with AIDS or ARC received anti-viral therapy, and the effect of zidovudine on markers was correlated with outcome. The markers studied were CD4, p24 antibody, B2 microglobulin, neopterin and p24 antigen. The entry criterion were HIV disease, a CD4 lymphocyte count >2OO/ul, and treatment with open-label zidovudine. Of the 90 patients, 87 were male and three female; p24 antigen was present in 5946, p24 antibody in 63%, and the CD4 count was >200/ul in 90%. By 17 months, 56 of 90 died. The median follow-up of those who survived, 34 of 90,was 25 months. After 12
355
weeks of zidovudine treatment, there was an increase in the CD4 lymphocyte count and decreases in p24 antigen, B2 microglobulin, and neopterin levels. The baseline neopterin level had the strongest predictive power of the effect of therapy with zidovudine. A poor prognosis was associated with a raised neopterin, AIDS and age >45 years at the outset. If these three values are controlled, then over the period of 12 weeks a decrease in CD4 count and an increase in serum microglobulin were the only good predictors of death. The value of B2 microglobulin at 12 weeks of therapy divided participants into good responders and bad responders. It is not clear why neopterin, a marker of monocyte activation, was a good predictor at the outset of therapy, but not after 12 weeks of therapy. In contrast, the CD4 count and B2 microglobulin level were better predictors when treatment had begun. Shoenfeld (FB83) looked at the effect of zidovudine therapy over a short period of 12 weeks in the context of four trials: zidovudine versus placebo, zidovudine in three dose levels; zidovudine versus placebo in patients with AIDS and ARC, and patients being treated with dextran sulphate-effectively a placebo since it is not absorbed. Data were collected at baseline and over 12 weeks of therapy to see if there was an increase in CD4 counts. There was an increase in CD4 counts which emphasizes that in the context of zidovudine, only a short period of study is required. Thus, CD4 counts can be used in phase I1 studies to see which drugs to study. Gail (FB86) reported the effect of therapy on the national epidemic in the United States. There has been a fall-off from the projected curve, i.e. a difference between the projected curve of AIDS incidence and the curve of AIDS incidence. It is questioned as to whether prevention programmes are resulting in a reduced number of people becoming infected. However, if one assumes that no-one was infected from 1982, there is still an improvement in the curve of AIDS incidence. The flattening occurs from mid-
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
356 S A N FRANCISCO SUMMARIES C. A. LEE 1987. It is possible to calculate the percentage of individuals who would need to be prescribed zidovudine to account for such a flattening. The calculated amount for 1988 is 48%, but the actual percentage is 38%. Thus, although zidovudine prescription accounts for some improvements in the AIDS incidence curve, there are other factors. Griensven (a Lecture during the Plenary Session) reviewed risk factors and HIV progression. The 11-year progressions to AIDS of 52% in the San Francisco cohort was the longest progression study. In the international registry of seroconverters reported by Biggar, there was a 40% progression rate to AIDS at 7 years and &IS was more rapid if there was sex with a person with AIDS. In a cohort of 319 haemophiliacs reported by Goedert, 64 older patients had a progression rate of 43%, 130 adolescents a progression rate of 27%, and 125 children a progression rate of 13%. Progression was 50% at 7 years in blood transfusion recipients and more rapid if the blood transfusion recipients were older or if the donor developed AIDS soon after the blood transfusion. In a cohort of 382 IVDUs, the progression rate to AIDS was relatively slower-15% at 6 years, presumably because these patients were younger. Amongst 159 females prostitutes in Nairobi, 80% progressed to CDC IV within 44 years. It was noted that the National Cancer Institute progression rate had reduced, and that the incidence of AIDS in Europe had fallen-off from mid-1988. The survival of AIDS patients was also improving: in San Francisco in 1985, the median survival was 10 months, but in 1987 the median survival was 15 months. Thus the clearly identified risk factors were age and the disease state of the index case. The only proven intervention at present was zidovudine therapy. The incubation period was a median 10 years. It was considered that following the reduction in AIDS cases due to zidovudine therapy, there would follow a rise in AIDS cases due to other causes, e.g. lymphoma. A new feature of the Sixth World AIDS
Meeting was a Rapporteur or Summary Session on the final day. Lifson summarized Track C, Epidemiology and Prevention. He discussed the importance of genital ulcers, general trauma and exposure to blood as risk factors in heterosexual transmission. For IVDUs, HIV transmission was increased in individuals using ‘crack’ since they were more likely to proceed to intravenous drug use. The blood-borne transmission epidemic in Roumania secondary to shared needles was discussed. An abstract had also been presented (ThC48) recording the spread of HIV from a Russian baby to mother from stomatitis in the baby to cracked nipples in the mother. The similarity in progression rates of homosexuals in San Francisco at 53% (1 1 years) and haemophiliacs in London at 52% (10 years) was commented on. The co-factors which had been shown to influence HIV progression were: older age, continued drug use and smoking. The role of CMV remained controversial. The impact of anti-viral and prophylactic therapy had made comparison of progressions difficult. The sero-prevalence patterns were changing throughout the world: young people, adolescents, were increasingly becoming infected in North America; in Central and South America the disease was changing from the type I to type I1 pattern with a declining male to female ratio; in Europe and Eastern Europe infection was occurring in IVDU and secondary to shared needles; in Africa there was spread from the urban areas to the rural areas; there was spread in Asia and the Western Pacific with 20% prostitutes in Bombay infected, and a spread in Thailand prostitutes making heterosexual spread a possibility. The major recent development had thus been the effect of therapy on the progression of HIV disease and the establishing of surrogate markers to assess the effect of therapy. However, this is in the context of the developed world-in the under-developed world, HIV continues to spread into areas previously unaffected, e.g. Eastern Europe and India. T h s meeting in San Francisco was
NATURAL HISTORY OF HIV AND AIDS
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
inevitably pre-occupied with the natural history in the homosexual epidemic. The concern of the global pandemic is that the major impact is still to come, the gap be-
357
tween the rich and poor is increasing and zidovudine is more expensive than most can afford.
AIDS Care: Psychological and Sociomedical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
Natural history of HIV and AIDS C. A. Lee
a
a
Consultant Haematologist, Katherine Dormandy Haemophilia Centre and Haemostasis Unit , Royal Free Hospital , London, UK Published online: 25 Sep 2007.
To cite this article: C. A. Lee (1990) Natural history of HIV and AIDS, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 2:4, 353-357, DOI: 10.1080/09540129008257752 To link to this article: http://dx.doi.org/10.1080/09540129008257752
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
AIDS CARE,VOL. 2, NO.4, 1990
353
Natural history of HIV and AIDS
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
C. A. LEE Consultant Haematologist, Katherine D m a n d y Haemophilia Centre and Haemostasis Unit, Royal Free Hospital, Londg UK
Introduction This conference has reported updates of previously well-documented cohorts of homosexuals and haemophiliacs. A new development has been the reports of progression in intravenous drug users (IVDU) and African women. There has been an explosion in sero-prevalence data with two new areas of concern: Eastern Europe and India. Many workers have reported on the influence of treatment on progression rates, and there has been a great effort to establish surrogate markers which may measure the effect of treatment. The disease was set in context at an Introductory Seminar ‘Comprehensive Management of HIV Disease’ during which Ressler spoke on natural history. He pointed out that in the US, AIDS incidence had levelled off and there was a delay in the progression from asymptomatics to CDC IV. This was in part secondary to anti-viral treatment and anti-pneumocystis (pcp) primary prophylaxis. Progression rates in the most reliable San Francisco cohort were 50% at 10 years, and the CD4 count remained the best surrogate market. H N disease should be considered as a ‘chronic ongoing viral disease’ and similar to many other chronic medical conditions, e.g. diabetes and hypertension. Hessol reported on the San Francisco cohort (ThC33). This is a group of 359 men who were amongst 6705 studied during 1977-80 as part of a mal of hepatitis B
vaccine. There was a first anti-HIV positive serum in 135 of these men. These patients have been subject to annual clinical review. Since 1986 regular T subsets have been measured and the clinical outcome (asymptomatic; ARC-candida, leukoplakia, weight loss and fever, or AIDS) monitored. Depending on the year of seroconversion 1977-80, 1981-83, 1984-86 and 1986, the percentage of patients developing AIDS is 61%, 42%, 29% and 0%. The Kaplan-Meier estimate of progression was 49% at 10 years, and 53% at 11.1 years. The actual progression in this cohort diverges from the modelled progression, suggesting an influence of treatment. Forty-five per cent of the cohort are now receiving zidovudine and 43% aerolized pentamidine. It is however difficult to discern the precise effect of treatment from other factors. Pedersen (ThC34) gave an update of 162 anti-HIV positive Danish .patients in many of whom details of the original seroconversion illness was known. These patients had a known date of seroconversion defined as the mid-point between the last negative and first positive anti-HIV. The great majority were male homosexuals. The progression end-points were recurrence of p24, CD4 less than 200/ul, and development of AIDS. Five years from seroconversion 50% had progressed to a CD4 count less than 200/ul and 22% had progressed to AIDS. Amongst those who had endured a
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
354
SAN FRANCISCO SUMhiARIEs. C A. LEE
more severe, protracted seroconversion illness at 5 years, 65% progressed to immunodepression and 38% to AIDS. In contrast, those with less severe symptoms at seroconversion, at 5 years 36% progressed to immunodepression, and 6.5% progressed to AIDS. The MACS (Multicenter AIDS Cohort Study) was reported by Visscher (ThC35). This has 5000 participants and of those 1809 seropositive at entry, 518 (27.4%) have AIDS. The incidence of AIDS per 100 persons per 6 months is 4.2%. This incidence has levelled off since the second half of 1986. Clearly treatment has contributed to this levelling off in the incidence of AIDS. However, since treatment was not in use until the second half of 1987, other factors may have contributed to this slowing of progression. Progression in a cohort of IVDUs by Rainer (ThC36) determined the effects of cessation of drug use. Three hundred and fifty five IVDUs were recruited in 1984, and they did not receive anti-viral therapy. Progression to AIDS was considered in three groups: patients on methadone maintenance, persistent IVDU, and former IVDU. Progression to AIDS and symptomatic disease was much faster in those continuing to inject drugs. As Anzala (ThC37) pointed out, there has been little data on progression in women or African people. A cohort of Nairobi prostitutes was described, which had been established in 1985-90. There were 1,200 women, and in a selected group of 184 followed at 6 monthly intervals who were initially seronegative, 163 seroconverted. The median time taken to progress from asymptomatic to advanced disease was 36 months, and the median time to progress to AIDS was 44 months. There was no correlation with the length of time of prostitution, contraceptive use or pregnancy. There was some correlation with condom use. It is not clear why the progression to symptomatic disease and AIDS should be so rapid in African women. A national cohort of haemophiliacs was
presented by Schinaia (ThC38). This is a multicentre study with 499 participants. Patients were stratified into three groups: age (13 years, 13-34 years. >34 years; type of haemophilia A or B; zidovudine treatment, or no treatment. For the whole cohort, the 5 year progression was 15% and patients aged >34 years had faster progression rates. In contrast the type of haemophilia and zidovudine treatment had no effect on progression rates. Ragni (ThC642) provided a0 update on a cohort of haemophiliacs from Pennsylvania. These haemophiliacs seroconverted between 1978 and 1986. The progression to AIDS was 42%, and to CDC IV alone 11%. PCP had occurred in 4096, but whereas prior to 1989 it had occurred in 52% of AIDS diagnoses, since 1989 it occurred in only 10%. Furthermore, the survival time of haemophiliacs with AIDS who were treated with zidovudine and pentamidine was almost twice that of those diagnosed with AIDS in the pre-treatment era. Lee (ThC641) provided a 10-year follow-up of a cohort of 111 haemophiliacs from the Haemophilia Centre, Royal Free Hospital, London. These patients seroconverted between October 1979 and July 1985. For the 63 patients for whom there was a precise date of seroconversion, the 10 year progression rate of AIDS was 52% (Cl, 34, 70) and to symptoms 87% (C1 75, 99). The median survival time of patients with AIDS was 15 months (range 0-36 months). The therapeutic interventions which could have influenced progression and survival were: prescription of zidovudme since August 1987, secondary prophylaxis with pentamidine since March 1988, and primary prophylaxis with pentamidine since February 1989. This had resulted in improved 18 month survival for AIDS: 33% (C1 6, 59) before August 1987, and 49% (C1 21, 77) since August 1987, Two female partners had become anti-HIV positive and 13 babies (all anti-HIV negative) had been conceived at the time the father was anti-HIV positive. Royce (ThC39) reported on the effect
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
NATURAL HISTORY OF HIV AND AIDS
of cigarette smoking and progression to AIDS. Smoking increases the CD4 lymphocyte count independently of HIV infection. Three hundred and eighty six seropositive men were studied and amongst non-smokers the progression rates to thrush, AIDS and deaths were respectively 39%, 27%, and 12%. Amongst smokers the respective rates were 50%, 33%, and 15%. Even when CD4 was controlled the rates were s t i l l higher in smokers. The reason for this risk factor is not known, although there was some correlation between the number of sexual partners and smoking. Lange (FB81) reviewed the surrogate markers that could be used to measure the effect of anti-viral therapy on clinical progression. The decline in p24 shows the antiviral effect, but can only be used in a subset of data. Zidovudine produces a reduction in plasma viraemia, but this is technically a cumbersome method. Although the pcr technique can be used to assess anti-viral therapy, problems of quantitation are not solved. Zidovudine produces a decline in the B2 microglobulin level. It is possible that the type of biological variant of HIV may have prognostic sigruficance. Viral drug sensitivity or resistance is a problem of increasing concern: 16 or 18 patients showed mutations of codon 215 after 2 years treatment. Jacobson (FB82) reported on the important use of serum markers as candidate surrogate markers for the effect of antiretroviral therapy in delaying progression. Ninety patients with AIDS or ARC received anti-viral therapy, and the effect of zidovudine on markers was correlated with outcome. The markers studied were CD4, p24 antibody, B2 microglobulin, neopterin and p24 antigen. The entry criterion were HIV disease, a CD4 lymphocyte count >2OO/ul, and treatment with open-label zidovudine. Of the 90 patients, 87 were male and three female; p24 antigen was present in 5946, p24 antibody in 63%, and the CD4 count was >200/ul in 90%. By 17 months, 56 of 90 died. The median follow-up of those who survived, 34 of 90,was 25 months. After 12
355
weeks of zidovudine treatment, there was an increase in the CD4 lymphocyte count and decreases in p24 antigen, B2 microglobulin, and neopterin levels. The baseline neopterin level had the strongest predictive power of the effect of therapy with zidovudine. A poor prognosis was associated with a raised neopterin, AIDS and age >45 years at the outset. If these three values are controlled, then over the period of 12 weeks a decrease in CD4 count and an increase in serum microglobulin were the only good predictors of death. The value of B2 microglobulin at 12 weeks of therapy divided participants into good responders and bad responders. It is not clear why neopterin, a marker of monocyte activation, was a good predictor at the outset of therapy, but not after 12 weeks of therapy. In contrast, the CD4 count and B2 microglobulin level were better predictors when treatment had begun. Shoenfeld (FB83) looked at the effect of zidovudine therapy over a short period of 12 weeks in the context of four trials: zidovudine versus placebo, zidovudine in three dose levels; zidovudine versus placebo in patients with AIDS and ARC, and patients being treated with dextran sulphate-effectively a placebo since it is not absorbed. Data were collected at baseline and over 12 weeks of therapy to see if there was an increase in CD4 counts. There was an increase in CD4 counts which emphasizes that in the context of zidovudine, only a short period of study is required. Thus, CD4 counts can be used in phase I1 studies to see which drugs to study. Gail (FB86) reported the effect of therapy on the national epidemic in the United States. There has been a fall-off from the projected curve, i.e. a difference between the projected curve of AIDS incidence and the curve of AIDS incidence. It is questioned as to whether prevention programmes are resulting in a reduced number of people becoming infected. However, if one assumes that no-one was infected from 1982, there is still an improvement in the curve of AIDS incidence. The flattening occurs from mid-
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
356 S A N FRANCISCO SUMMARIES C. A. LEE 1987. It is possible to calculate the percentage of individuals who would need to be prescribed zidovudine to account for such a flattening. The calculated amount for 1988 is 48%, but the actual percentage is 38%. Thus, although zidovudine prescription accounts for some improvements in the AIDS incidence curve, there are other factors. Griensven (a Lecture during the Plenary Session) reviewed risk factors and HIV progression. The 11-year progressions to AIDS of 52% in the San Francisco cohort was the longest progression study. In the international registry of seroconverters reported by Biggar, there was a 40% progression rate to AIDS at 7 years and &IS was more rapid if there was sex with a person with AIDS. In a cohort of 319 haemophiliacs reported by Goedert, 64 older patients had a progression rate of 43%, 130 adolescents a progression rate of 27%, and 125 children a progression rate of 13%. Progression was 50% at 7 years in blood transfusion recipients and more rapid if the blood transfusion recipients were older or if the donor developed AIDS soon after the blood transfusion. In a cohort of 382 IVDUs, the progression rate to AIDS was relatively slower-15% at 6 years, presumably because these patients were younger. Amongst 159 females prostitutes in Nairobi, 80% progressed to CDC IV within 44 years. It was noted that the National Cancer Institute progression rate had reduced, and that the incidence of AIDS in Europe had fallen-off from mid-1988. The survival of AIDS patients was also improving: in San Francisco in 1985, the median survival was 10 months, but in 1987 the median survival was 15 months. Thus the clearly identified risk factors were age and the disease state of the index case. The only proven intervention at present was zidovudine therapy. The incubation period was a median 10 years. It was considered that following the reduction in AIDS cases due to zidovudine therapy, there would follow a rise in AIDS cases due to other causes, e.g. lymphoma. A new feature of the Sixth World AIDS
Meeting was a Rapporteur or Summary Session on the final day. Lifson summarized Track C, Epidemiology and Prevention. He discussed the importance of genital ulcers, general trauma and exposure to blood as risk factors in heterosexual transmission. For IVDUs, HIV transmission was increased in individuals using ‘crack’ since they were more likely to proceed to intravenous drug use. The blood-borne transmission epidemic in Roumania secondary to shared needles was discussed. An abstract had also been presented (ThC48) recording the spread of HIV from a Russian baby to mother from stomatitis in the baby to cracked nipples in the mother. The similarity in progression rates of homosexuals in San Francisco at 53% (1 1 years) and haemophiliacs in London at 52% (10 years) was commented on. The co-factors which had been shown to influence HIV progression were: older age, continued drug use and smoking. The role of CMV remained controversial. The impact of anti-viral and prophylactic therapy had made comparison of progressions difficult. The sero-prevalence patterns were changing throughout the world: young people, adolescents, were increasingly becoming infected in North America; in Central and South America the disease was changing from the type I to type I1 pattern with a declining male to female ratio; in Europe and Eastern Europe infection was occurring in IVDU and secondary to shared needles; in Africa there was spread from the urban areas to the rural areas; there was spread in Asia and the Western Pacific with 20% prostitutes in Bombay infected, and a spread in Thailand prostitutes making heterosexual spread a possibility. The major recent development had thus been the effect of therapy on the progression of HIV disease and the establishing of surrogate markers to assess the effect of therapy. However, this is in the context of the developed world-in the under-developed world, HIV continues to spread into areas previously unaffected, e.g. Eastern Europe and India. T h s meeting in San Francisco was
NATURAL HISTORY OF HIV AND AIDS
Downloaded by [The University of Manchester Library] at 23:33 24 January 2015
inevitably pre-occupied with the natural history in the homosexual epidemic. The concern of the global pandemic is that the major impact is still to come, the gap be-
357
tween the rich and poor is increasing and zidovudine is more expensive than most can afford.
