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February 2004 ECI/HIVAN HIV/AIDS Journal Club
Judith King. February 2004. HIVAN Media Office.
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The first session of the Journal Club's 2004 series was held on 6th February at the Nelson R Mandela School of Medicine, UKZN, and featured presentations by Professor Jerry Coovadia on "Alternatives to HIV RNA concentration and CD4 count to predict mortality in resource-poor settings" and Ms Uvani Bodasing on "Resistance to anti-HIV drugs created by good pill-takers - not poor pill-takers".
Prof Coovadia began his presentation with a brief overview of recently published data on the topic of anti-HIV drug treatment and patterns of resistance in poor communities, as well as mention of current debate on the accuracy of HIV-prevalence and AIDS mortality statistics. The relevant references included:
Taha, E. et al: Lancet 2003; 362: 1171-77 Williams, B.G. and Dye, C.: Science 2003, 301 1335-37
The current debate on this topic had been sparked by a controversial article published in The Spectator by author Rian Malan questioning whether, [as summarised by journalist Kerry Cullinan of Health-e News, "AIDS Stats - Just how many of us are dying?", 22 January 2004]: "...AIDS deaths have been exaggerated and whether there is a conspiracy to deliberately distort these deaths to ensure that huge resources are allocated to AIDS."
Cullinan points out: "Actuaries concede that with more information about the epidemic, the prevalence in the population is probably lower than initially projected. The Actuarial Society of Southern Africa (ASSA) is currently revising its figures and expects its new model to be available in late February. This model is expected to produce a population prevalence that is around 90% of the estimates of the current 2000 model."
In her article, Cullinan also quotes Professor Carel van Aardt from Unisa's Bureau of Market Research, who draws from the available death registration data, as saying that his demographic research division estimates an overall 2003 HIV-prevaence rate of 14.87%, but emphasises the need to examine the differential stage of the HIV epidemic in each province rather than to focus solely on a national figure. For the full transcript of Cullinan's article, visit http://www.health-e.org.za/news/article.php?uid=20030919
Prof Coovadia commented that in making inferences from the findings of these studies and the concomitant discourse being shaped through the media, one should bear in mind that no practice works as perfectly as researched theories. "It is widely acknowledged that projections for the South African experience of the epidemic as derived from ante-natal clinic studies and the recent HSRC household survey are flawed, and that the truth is probably somewhere in between these figures." He also cited the latest UNAIDS / WHO publication entitled "AIDS Epidemic Update, December 2003" as a useful reference for the latest estimates, which show an increasing number of people living with HIV/AIDS globally. (See www.unaids.org)
He then turned to the study undertaken by Mofenson, L. et al, (The Lancet Vol 362, November 2003, 1625-27) as the primary reference for this presentation, which looked at cheaper markers for viral load tests, including total and CD4 lymphocyte counts as well as serum albumin concentration assays. These indicators appeared to be simple and cost-effective for use in resource-poor settings, particularly in children. Further research would need to be conducted to demonstrate the reliability of these findings and their applicability in the South African context. Professor Willem Sturm noted that there are results available from studies on adults in South Africa.
Ms Uvani Bodasing, a junior biomedical researcher working at UKZN's Medical School, then presented on a paper published by Bangsberg, D.R. et al in AIDS September 2003 17: 1925-32, which claims that resistance mutations to anti-HIV drugs are more likely to develop in patients who take most of their medications rather than in those who do not. She explained that these prospective trials, conducted on a REACH cohort of homeless individuals in San Fransisco, USA, showed mutation as well as incomplete viral suppression in moderate to high adherence case-studies. Previous studies relating to high levels of adherence and drug resistance had been cross-sectional, but this study showed that drug resistance mutations were high in patients who had moderate to good levels of adherence. The more pills that were taken, the more drug selection pressure was increased and the greater the resistance caused - but this occurred only in the case of ongoing viral replication.
Quoting comment sought from HIV/AIDS drug-adherence specialist Professor Gerald Friedland of Yale University's School of Medicine, Ms Bodasing reported that his view of the article was positive, although he warned that it could be misleading because the issues underlying adherence and viral interaction are complicated, and that the achievement of 100% adherence is still the goal for HIV/AIDS practitioners and patients.
The factors that have typically confounded measurements of adherence in studies undertaken in the developed world have involved determinants such as patient characteristics, (i.e. demography of age, sex, race/tribe/language and socio-economic status); information, knowledge and cognition; motivation in terms of beliefs, depression, drug use; behaviour skills (pill-taking and scheduling); provider-expertise; trust between clinicians and patients; the complexity of regimens; toxicity and side-effects, disruption; disease stage; social isolation and the nature of the clinical setting.
Once comment was invited from the floor, Professor Willem Sturm observed that when an ineffective drug does not ensure full viral suppression, the virus within the organism responds by mutating into a resistant form. Ms Mandisa Mbali asked whether self-report, as was deployed for data-gathering and analysis in this study, could be regarded as a valid method of established an accurate profile of adherence. Ms Bodasing replied that although self-report could be, in some instances, subjective and to an extent untruthful, the more "objective" method of pill-counts was also flawed, in that sharing of medications or failure to produce the pills for counting during a consultation could also prove unreliable; it was generally accepted that the use of both methods in combination was best in terms of monitoring.
The meeting concluded with the general observation that the "wild" virus was stronger or "fitter" than the mutated virus, and that, as no standardised, categorical measurement for ideal adherence was yet available, all the current research data had to be regarded as "naive". |
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