The basic tenets for the prevention of any disease have to be based on a good understanding of the aetiology as well as the natural progression of that disease. Chapter 2 of this report reflected the split of the panel into two factions around the aetiology of AIDS. The diametrically opposing views on the causal link between HIV and AIDS made the deliberations on prevention strategies extremely challenging. This split on aetiology produced the unavoidable consequence that the deliberations on the prevention of AIDS necessarily had to take place in two parallel streams. Some proponents of HIV as the primary cause of AIDS declared their disinterest in discussing preventive strategies with panellists who did not believe that HIV causes AIDS. Similarly, panellists who do not support the causal link between HIV and AIDS argued that prevention strategies based on this assumption were doomed to fail. The report will therefore present two sets of recommendations in order to capture the arguments accurately.
In support of the view that the severe immune deficiency that is currently observed in Africa was due to exposure to toxins and a variety of stressors of a chemical, biological, and sometimes physical nature, Dr Giraldo emphasised that prevention should focus on these stressors and not on an innocent virus. He expressed scepticism about the prevention strategies recommended by the CDC since these had been published even before Prof Montagnier had isolated the virus. Prof Montaigner countered this line of argument by highlighting the fact that these recommendations were based on epidemiological evidence of how transmission occurred. This approach was scientifically acceptable and was the basis for interventions for many other diseases.
Pursuing the argument for a toxicological basis for AIDS, Dr Duesberg argued that despite propaganda generated from the west on what the real cause of AIDS is, there was enough evidence that the epidemic was concentrated on specific groups of people who had in common malnutrition, poor sanitation and constant exposure to environmental toxins.
Dr Giraldo recommended that the first point of entry for prevention was to stop the media-generated hysteria on AIDS. He argued that this hysteria and fear contributed to suppression of the immune system of people who were told that they are HIV-positive on the basis of unreliable tests and were doomed to die. The recommendations, he suggested, should focus on:
For those whose immune system had been compromised already, it was important to detoxify their bodies using naturally occurring anti-oxidants such as vitamins A, C, E, glutathione and others. The use of immune-boosters to stimulate the immune system was also recommended.
In a passionate presentation, Dr Giraldo submitted that the focus on HIV was distracting leaders in the developing world from focussing on the real causes of AIDS — such as poverty, malnutrition and poor sanitation. He argued that the developed world was forcing African governments to focus on the use of anti-retroviral drugs, which did nothing more than compound the problem. He urged the South African government to resist the violation of its integrity by the international community and to continue its quest for African solutions to this problem.
Dr Bertozzi shared his experiences on his work on the epidemiology of the disease in Africa. He shared his experiences from several countries in Africa, arguing that although there were gaps in the knowledge on the epidemiology of this epidemic, there were clear transmission patterns and groups, and people at risk could be identified even on the basis of such limited knowledge. His experience had convinced him that sub-Saharan Africa is 'on fire' due to this epidemic. The nature of the problem was so urgent that emphasis had to be placed on what could be done now to halt the spread of this epidemic. To Dr Bertozzi South Africa was like “a building that is burning and our first focus needs to be on getting people out of the building and putting out the fire. We will have time over the decades to come to debate the mechanisms of how the fire was started….”
In support of this view, Mr Scondras argued that historically public health had benefited very little from arguments on aetiology but more benefit had been derived from the application of proven therapeutic and prevention techniques vis-à-vis any illness. Emphasis should therefore be placed on the wide-scale implementation of effective interventions in a controlled and sustainable manner.
There was consensus that whilst the search for scientific solutions was being pursued, everything should be done to slow the spread of the disease and to mitigate its impact.
Sections 2.3 and 2.4 of this report captured the submissions on the causes of AIDS from the point of view of those panellists who do not subscribe to the notion that HIV causes AIDS.
The recommendations listed below were proposed as necessary and sufficient to combat all the risk factors that are the real cause of AIDS:
Panellists who support the causal link of HIV to AIDS proposed that preventive strategies be linked more specifically to the different modes of transmission of HIV/AIDS. These panellists did, however, also support some of the more general medical and public health interventions listed in section 6.1.1 above as critical to ensuring a healthy society.
Three specific modes of transmission of HIV/AIDS were identified in Chapter 2 of this report as follows:
Dr Fiala suggested that although he did not support the view of the sexual transmission of HIV, the above recommendations did make sense as long as the focus was on a broader approach to healthy sexual habits which encompass prevention of unwanted pregnancy, rather than a single focus on HIV.
Panellists who believe that infants can be infected during pregnancy and delivery and through breast-feeding provided several recommendations on preventing these forms of transmission from mother to infant.
Dr Stein cautioned that the recommendations on breastfeeding had to be done in such a way that the long-established benefits of breastfeeding for other women are not undermined.
Evidence of the efficacy of anti-retroviral drugs is obtained from randomised-controlled trials as well as systemic reviews.
(a) Zidovudine (AZT) – Efficacy and toxicity
The efficacy of AZT in preventing vertical transmission of HIV has been sufficiently demonstrated in several randomised-controlled trials. The reduction in the risk of transmission varies from 37% to 67% in the different studies.
No serious side effects in pregnancy were detected in the above studies and in the infants born to these mothers followed up to the age of four years. There is enough evidence to show that the benefits outweigh the risks, and it is recommended that this drug be provided to women in pregnancy where resources are available to do so.
(b) Nevirapine – Efficacy and toxicity
The HIVNET 012 trial, a randomised-controlled trial comparing Nevirapine and AZT, was conducted in Uganda. Nevirapine use resulted in a decrease in vertical transmission of 48% (95% CI 17 to 60%). The regime is easy and cheap to administer.
Concerns have been raised over the development of resistance in women who have been exposed to a single dose of Nevirapine. Further research on the implications of this resistance is necessary.
There are concerns regarding the impact of breast-feeding on the transmission
of HIV. Follow-up studies on mother–infant pairs where anti-retroviral
drugs have been used show a reversal of efficacy when breast-feeding continues
beyond six months. More research in this area is warranted. In the interim,
the best feeding advice would be formula feeding for those who can afford it
and exclusive breast-feeding with early weaning when women cannot afford to
purchase formul
(c) Combination anti-retroviral use for MTCT prevention
Good evidence has been presented from the PETRA trial. This randomised trial assessed the combination of AZT and Lamivudine (3TC). This regimen resulted in a 48% risk reduction of HIV transmission.
The role of caesarean section has been tested in a recent randomised-controlled trial (RCT). This demonstrated an 87% reduction in vertical transmission in the group randomised to caesarean section. In a further analysis of this subgroup, which focused on women who had had prior exposure to AZT, the effect of caesarean section became less dramatic.
This intervention however, cannot be recommended as policy in South Africa for several reasons:
The evidence from a RCT indicates that vaginal lavage is only of value if the labour is longer than four hours in duration. Reasonable guidelines would include not rupturing membranes in active labour unless there is an obstetric or foetal indication. Invasive monitoring techniques are not recommended. Routine performance of an episiotomy is also contraindicated.
Dr Sonnabend pointed out that the control of AIDS infections should not be seen in isolation from other morbidity factors that exist in society, but should be considered in the context of broader social conditions. There is a need to improve overall public health measures in order to improve the health of the population in general. The control of endemic diseases such as TB, malaria, helminthic infections and diarrhoeal diseases and the general provision of clean water have a major impact on the reduction of morbidity and on the spread of the AIDS epidemic in the population. Although HIV infection is diagnosed by antibody tests, other very important baseline tests need to be conducted to provide an indication of the presence of other infections, namely, the Skin test for TB, as well as tests for syphilis, toxoplasmosis and hepatitis A, B and C. For female patients, tests for chlamydia, gonorrhoea and varicella are important.
After a diagnosis of HIV infection, it is necessary to determine the risk for opportunistic infections. Patients with a declining CD4 are more susceptible to opportunistic infections and therefore prophylactic treatment becomes more appropriate with declining CD4 counts. Drugs such as Bactrim (cortrimaxozole) to prevent general bacterial infections and Isoniazid (INH) for tuberculosis are inexpensive and affordable for prophylaxis.
Dr Sonnabend presented a convincing case for prophylactic therapies for the treatment of opportunistic infections rather than treating the so-called surrogate markers.
The most important step is to determine the common causes of mortality in AIDS and determine the most appropriate prophylactic intervention strategy or drugs. For example, if much of the AIDS mortality is due to TB, a prophylactic regimen for tuberculosis, such as INH, will be the most suitable intervention strategy.
Generally, the earlier the treatment is started, the better the chance of preventing and managing opportunistic infections. There are two types of prophylaxis, namely:
The most common opportunistic infections are cryptococcal meningitis, TB, bacterial, yeast and parasitic infections, Pneumocystis carinii, as well as cervical cancer associated with the human papilloma virus.
A frequent question is how early prophylactic therapy against opportunistic infection should be initiated after HIV infection/diagnosis. Work done in the Ivory Coast suggests that early intervention for opportunistic infections with co-trimoxazole is beneficial and effective. Where facilities exist for conducting a CD4 cell count, an additional guideline is that anyone with a CD4 cell count of less than 500 should be given prophylactic treatment.
INH is the most effective prophylactic drug against TB, but care should be taken to monitor any emergence of resistance against INH. The recommendation for the prophylactic treatment of TB should only be considered, however, where there are facilities for counselling, testing for and excluding active TB infections. Moreover, it is recommended that INH prophylaxis be considered only in countries with a well-established TB control programme, without which INH prophylaxis might lead to further resistance to TB. The recommendation thus needs to be adapted to country specificities.
Bactrim is the most generally used prophylactic drug against many bacterial infections. It is an inexpensive drug that many developing countries can afford.
There is some debate around whether one should institute primary prophylaxis for cryptococcal infections. If it is instigated, the drug of choice is Fluconazole. A concern is the possible development of resistance to the drug, which would reduce its usefulness when needed in the future treatment of the patient.
For cytomegalovirus (CMV) disease, the drug of choice for prophylaxis is Ganciclovir, which is useful for patients with CD4 counts lower than 50. However, this drug is expensive and is beyond the means of many patients.
For prophylactic therapy against mycobacterium avium, the drugs of choice are Perithromicin and Rifobutin.