Just When You Thought the Global HIV/AIDS Picture Couldn’t Get Any Worse — It Did
What could a vaccine do?
As people in the North America, Western Europe and Australia begin to live longer with HIV and AIDS (and even begin to savor the first wafts of what might turn out to be a kind of cure), the bitter contrast between the haves and the have nots grows all the more stark. The United Nations reports that a staggering 16,000 people are newly infected with HIV each day, and a total of 30 million people are now estimated to be living with HIV worldwide. TAGs Spencer Cox has transcribed the dire statistics straight from the source. His report from this past autumns ICAAC plenary reminds us how far weve yet to go — and offers the first etchings of a road map, even while those living the nightmare scenario see only political posturing and empty promises.
Despite last years wistful pronouncement of “The End of AIDS,” observers world-wide report that the global HIV pandemic continues to pick up steam. In September, Dr. Peter Piot of the United Nations Joint Program on HIV/AIDS told delegates to the 37th Interscience Conference on Anti-microbial Agents and Chemotherapy (ICAAC) of the toll which HIV continues to extract world-wide.
Piot began his talk with the startling statistic that worldwide there are an estimated 16,000 new HIV infections each day (1,600 of them children); 90% of cases occur in developing countries; 40% among women and greater than 50% in persons between the ages of 15 and 25 years of age.
The number of cases of AIDS is still greatest in sub-Saharan Africa, South and South-east Asia, followed by Latin America, and then North America and Western and Eastern Europe.
| Global Infectious Causes of Death | ||
| 1996 | 1997 (est.) |
|
| Tuberculosis | 3.0 M | |
| Malaria | 1.7 M | |
| AIDS | 1.5 M | 2.3 M |
| Source: United Nations | ||
Dr. Piot described AIDS as now as common as malaria as a cause of death worldwide, with an estimated 1.5 million deaths annually. Despite the recent advances in new antiretroviral treatments in the developed world, AIDS mortality is dramatically accelerating, with one quarter of all deaths from AIDS having occurred in the last year alone.
The front line of the epidemic today is quite clearly Asia. For example, there are four million HIV-infected persons in India (most of these individuals infected within the last two to three years). Seroprevalence among Bombay sex workers is estimated to be 51%; STD clinic patients, 40%; pregnant women, 3%. In Sub-Saharan Africa, AIDS has been concentrated primarily in the Southern, East Coast and Central African countries, with pockets of disease in the Ivory Coast. HIV prevalence among pregnant women ranged from 17%-40% in these countries, the majority of mothers infected between the ages of 15 and 25.
Among Latin America countries, Brazil has the greatest number of HIV-infected persons; as many as 23% of gay men, 27% of sex workers and 60% of injection drug users being HIV-infected. In the state of Sao Paulo, the economic powerhouse of Brazil, AIDS is now the leading cause of death — even though Sao Paulo state now pays for triple combination therapy for “Paulistas” with an AIDS diagnosis.
The projected life expectancy has been reduced by as much as 25 years in countries in Sub-Saharan Africa where HIV is endemic. The economic and social impact of the epidemic in these countries will be devastating. AIDS is reversing any gains in human development made in this part of the world prior to the onset of the epidemic.
While Africa continues to have the most severe epidemic in the world, Piot warned that we are poised for a “new epidemic explosion” in Eastern Europe and parts of the former Soviet Union, where needle use and heterosexual transmission are the most frequent routes for the disease. A recent series in Newsday by Pulitzer-prize winning journalist Laurie Garrett noted that as a result of the collapsed public health system in nations of the former Soviet Union, infectious disease experts were forced to stand by as HIV infection rates increased by up to 300% annually. In addition, Piot warned, Asia — and particularly India — comprise the “front line of the epidemic,” with skyrocketing rates of new infections.
Piot also noted that HIV was contributing to the resurgence of other infectious diseases: tuberculosis rates, according to data from the UN, is rising in tandem with the HIV pandemic, “like its shadow.” Because the public health infrastructures and economies of the different countries and continents vary widely, the UN has developed a set of strategies for combating HIV infection world-wide.
Amidst all the dire statistics, Dr. Piot explained that significant gains had been made in the prevention of new infections in several parts of the world. In Switzerland, Thailand and Uganda, aggressive sex education (including information on sexually transmitted diseases and condom use) has been met with initial success. In Uganda, for example, rigorous prevention campaigns in prenatal clinics had reduced the HIV seroprevalence rate in pregnant women from 21% in 1990-1993 to 15% in 1994-1995. In Thailand, an aggressive behavioral modification among pregnant women and 21-year old military conscripts from 1989-1995 has led to a significant reduction in the rate of new seroconversions in these populations.
According to Piot, the UN program is also attempting to improve access to generic drugs in the developing world, and to assist in bringing antiretroviral therapy to those countries whose public health infrastructures and economies would permit their use. (This claim, however, sparks fury in the eyes of our Venezuelan ex-patriate translator — who is also the co-founder of a group (Aid for AIDS, 212.358.9715) that collects and distributes AIDS medicines to South American and the Caribbean PWHIVs. So apparently, alot of this is still just politically correct posturing and hollow lip service.) Piot also says that by working with the World Bank, the UN is making an effort to improve the public health infrastructure in other countries. The World Bank, it seems, is increasingly concerned that the AIDS epidemic is posing a significant barrier to economic development of “third-world” countries.
In his closing summary, Dr. Piot summed up the current situation with AIDS as being “very, very grim.” “None of us could have predicted this 15 years ago,” he said. “The AIDS epidemic,” he continued, “is far, far from over. And we will have to cope with it for many generations to come.”
Many observers believe that the only way that the world-wide epidemic can be brought under control is through the development of a vaccine to prevent infection. Dr. David Baltimore, soon to leave MITs Whitehead Institute to become the president of California Institute of Technology (Cal Tech) and chairman of the NIH AIDS Vaccine Research Committee (AVRC), reviewed the current approaches to vaccine development and the hurdles which still need to be overcome before a safe and effective candidate vaccine can move forward into large-scale human trials.
In a quick retrospective homage to effective vaccines strategies, Baltimore noted that some were successful because they stimulated T-cell memory; while others were successful because they induced an antibody-mediated response. The best historical models for antiviral vaccines, Baltimore explained, are the live, attenuated vaccine (à la the Sabin polio vaccine) and the whole, killed vaccine (à la the polio vaccine of Jonas Salk). Of the seven current approaches to the development of an HIV vaccine, the best results to date have been achieved with a live attenuated vaccine using the simian immunodeficiency virus (SIV) in monkeys. Baltimore was quick to point out, however, that even though some of these animals resisted infection with a highly virulent strain of SIV subsequent to vaccination, the vaccine itself caused disease in some of the animals.
Earlier approaches to HIV vaccines, which used recombinant subunit proteins of HIV (e.g., gp120 and gp160) have not proved effective in producing neutralizing antibodies to wild-type HIV. Other approaches to vaccine constructs include live vectors (pox and non-pox), pseudovirions, naked DNA, peptide epitopes and whole, killed viruses.
At this point in the presentation, Dr. Baltimore departed from the specifics of vaccine constructs to raise the practical question of “What could a vaccine do?” Specifically, if the gold standard — sterilizing immunity — is not currently a realistic expectation with an HIV vaccine, would a vaccine that reduced the initial multiplication of HIV (and resulted in a lower viral “set point”) enable the maintenance of a long-term low viral load which would lead to more long-term non-progressors — and a significant reduction in new transmissions?
In summary, Dr. Baltimore enumerated the requirements for a successful vaccine program; he especially emphasized the need to integrate the latest knowledge of HIV into the current vaccine development programs and that human testing of vaccine candidates “is integral.” Baltimore also pressed for better organization among government, university and industry entities. He then ended with a final plea for “creative, new ideas.”
In addition, Dr. Baltimore noted that the current government funding for the United States HIV vaccine effort is in excess of $100 million a year, and that the President of the United States and Secretary of Health and Human Services, Donna Shalala, have promised that “more funds could be found if they were needed.” At the present time the National Institute of Allergy and Infectious Disease and National Cancer Institute are committed to constructing a joint vaccine laboratory which is expected to be housed under a single roof at a vaccine-dedicated site by the year 2000. A search for a Director of the program is currently underway. Baltimore closed by stating that if a preventive vaccine is not developed soon, “it will not be a pretty future” for the world and we must “redouble our efforts to make vaccine efforts work.”
| The Future of AIDS | ||
| Previous Estimate 1996 |
Current Estimate 1997 |
|
| People with HIV or AIDS | 22.6 M | 30.6 M |
| Sub-Saharan Africa | 20.8 M | |
| South and Southeast Asia | 6.0 M | |
| Latin America | 1.3 M | |
| North America | 860,000 | |
| Western Europe | 530,000 | |
| East Asia and Pacific | 440,000 | |
| Caribbean | 310,000 | |
| North Africa, Middle East | 210,000 | |
| Eastern Europe, Central Asia | 150,000 | |
| Australia, New Zealand | 12,000 | |
| New Infections per Year | ||
| Total | 3.0 M | 5.8 M |
| Children | 350,000 | 580,000 |
| Deaths per Year | ||
| Total | 1.5 M | 2.3 M |
| Children | 350,000 | 440,000 |
Source: United Nations