Unanswered questions about AIDS
By Dr Walter Chin
April 22, 2001
Since the first cases of AIDS were detected two decades ago, scientists have learned a lot about this viral disease. Within a relatively short period of time, the virus (HIV) that caused AIDS was discovered and a test to detect it was developed.
Then the three routes by which the virus was transmitted (sexual intercourse, contaminated blood and other body fluids, and mother to infant during pregnancy) was learnt. Finally, drugs were brought into use that could slow the progress of, but which could not cure, the disease.
In spite of all that is knownabout HIV and AIDS, the AIDS epidemic continues almost unabated. Thirty-six (36) million people are now infected with the virus, while twenty-one (21) million have died. Of the 36 million infected, over 30 million are unaware of their infection.
The whole continent of Africa is extensively ravaged by the disease. It is projected that the life expectancy of many African countries will be reduced to around 30 years within this decade because of AIDS. These projections also apply to other countries such as India and Bangladesh.
There are still many unanswered questions about HIV/AIDS. One question is why in AIDS patients there is an increased risk of developing certain types of cancers and infections in comparison to other patients. AIDS patients, for example, are more likely to develop cancers such as non-Hodgkin's lymphomas and Kaposi's sarcoma, but not cancers of the breast, colon, and lung which are much more common in the rest of the population. This suggests that the impaired immune system in AIDS does not allow common cancers to develop.
Another intriguing point is that since the introduction of anti-HIV drugs, both non-Hodgkin's lymphoma and Kaposi's sarcoma have reduced in frequency, but Kaposi's much more so. It is not known why non- Hodgkin's lymphoma has not declined proportionately, but this is quite likely to become a significant problem, the longer HIV/AIDS patients survive. However, it is likely that with more successful treatment of AIDS patients, another set of cancers (Hodgkin's disease, testicular cancer, head and neck cancers) might increase in frequency. Another curious point of note is that AIDS patients are more prone to infections like pneumonia caused by uncommon organisms such as fungi. Why this is so is still not known.
Although the routes of transmission of HIV are known, it is not clear how the virus invades the body. It is thought that the virus is transmitted across a mucosal barrier and then infects monocytes, a form of white cell.
Within 36 hours, HIV travels through lymph vessels to lymph nodes and, within 4-5 days, to the rest of the lymph system. Normally, the level of virus in the circulation reaches a peak 3-4 weeks after infection.
Again, it is not known how the virus destroys the body's CD4 cells that are needed to combat invading infectious agents.
Although the infection induces a vigorous immune response that partially clears the virus and decreases the level, HIV is rarely, if ever eradicated. Knowing the way in which the virus travels in the body could provide the means of blocking it on in its journey and possibly preventing infection.
An extremely important question is, how is the immune system affected by HIV?
This question arises because there is widespread variation in the speed at which HIV infected persons develop AIDS. It is well known that some HIV infected persons may not develop AIDS until after a considerable period of time, while others become ill with AIDS fairly rapidly. In addition, there are groups of people who remained HIV negative despite having lived with infected HIV infected partners, while a group of sex workers was shown to have a reduced risk of HIV infection if they had remained uninfected after six years of high risk exposures.
The conclusion from the latter is that there might well have been some development of immunity at the mucosal sites. It would be valuable if the 'factors' responsible for this variation could be identified, as these could be used to develop vaccines or drugs to prevent the infection or to slow the progression of the disease.
There are some infected people known as long-term nonprogressors, who have lived with HIV without therapy for as long as 20 years. Again, researchers are trying to identify what in their immune system is responsible for this non-progression of the infection.
The HIV transmission rate from an infected mother to her baby is estimated to be from 25 to 40 per cent. Why do the other 75 to 60 per cent of infants escape infection? Not much research has been carried out to answer this question.
It is presumed that the viral load in the mother determines whether there will be transmission to the infant. As a consequence, antiretroviral drugs have been used during pregnancy to reduce the viral load in the mother, and decrease the risk of mother to baby transmission.
Since the mid-1980's, 15 drugs have been developed for use against HIV. These have been used in combinations of three or more, and have reduced the number of deaths and increased the life expectancy and quality of life of many.
The drugs have also reduced the incidence of mother to child transmission of HIV. However, HIV is so clever that many of those infected who have taken each of the 15 drugs at one time or another, are still not deriving benefit from them.
There is now some debate as to the best time to start anti-HIV therapy. Initially, in the mid-1990's, it was thought that early treatment offered the best chance of preserving immune function.
The policy then was to 'hit early, hit hard.' But it was realised eventually that the drugs did not completely eliminate HIV from the body, and they had dangerous side effects.
Moreover, it was likely that they would have to be taken for a lifetime. It is now recommended that treatment should be deferred until there are signs that the immune system is weakening. But questions such as what combinations of drugs should be started first and when, remain. One method now under trial is treating for specified periods of time, then restarting therapy in well-defined cycles, similar to some cancer therapy regimes. Studies are also in train to find out whether starting drug treatment soon after infection for a specified period only, might stimulate the immune system to produce a protective response.
Ultimately, preventive vaccination will be the most efficient and cost effective approach to halting the AIDS epidemic. Is a vaccine in the offing?
More than 70 vaccines have been tried out experimentally on people, but only one has reached the full stage of testing.
The others have produced levels of antibodies not regarded as adequate to guard against HIV infection, and have failed to stimulate the formation of so-called killer T cells (which attack and destroy HIV). At the present time, there is still a great deal of ignorance as to which antibodies produced in response to an HIV vaccine indicate the greatest likelihood of protection.
The dearth of knowledge suggests that a vaccine might not be available for at least 10 years.
Despite an extensive understanding of some aspects of HIV/AIDS, our knowledge of the interventions needed to prevent (by means of a vaccine) and cure HIV/AIDS remains weak.