September 25, 2000

"REALITIES" OF AIDS EPIDEMIC SHARED AT IHV SCIENCE MEETING

BALTIMORE, Md.--While the HIV virus continues to attack without discrimination, the whole world shares a moral imperative to help places hardest hit by the AIDS epidemic.

That clear "take home message" from AIDS-fighting leaders of Africa and the Carribean to top U.S. and European AIDS research scientists meeting in Baltimore, was a call for more "North-South"scientific partnerships, said University of Maryland Biotechnology Institute (UMBI) scientist William Blattner. "They gave us an unvarnished view of their complex experiences dealing with the hard realities of the epidemic in the developing world."

The unusual "HIV/AIDS in the Developing World" session was the first of its kind for the annual conference of UMBI's Institute of Human Virology (IHV), which dates back more than 20 years when director Robert C. Gallo, Blattner and other IHV scientists conducted AIDS and other research at the National Cancer Institute (NCI).

The IHV conference was attended by nearly 800 scientists earlier this month. For six days, most of the 130 HIV and cancer research speakers presented details of experimental AIDS vaccines, genetics of ever-more subtypes of mutating HIV strains, advances in treatments, and sobering statistics of a still ravaging world epidemic of nearly 40 million people infected.

Blattner is a veteran AIDS epidemiologist who with NCI in the mid-1980's helped define HIV transmission routes in the population. This year, he organized the developing world session as a follow up to the "message," he said, of the World AIDS Conference held in Durban, South Africa earlier this year. "One of the things that came out of Durban is that AIDS, unlike any other major disease, affects every country. We set this up at a high-end science meeting as a real opportunity for scientists to take to heart the immediacy of their research to those whose lives depend upon affordable therapies and an effective preventative vaccine," said Blattner. "The moral and ethical challenge to each scientist is how the fruits of research can get to those who are infected or at risk."

However, speakers from the developing nations warned that scientific "interventions"--such as the AIDS vaccines entering clinical trials in several nations of Africa, Asia, and Latin America, and the reduction in costs of anti-HIV drug therapies--although promising, are not clear cut answers in all the hot spots of the epidemic. Studies show that around the world HIV occurs in two major forms, and for HIV-1, the type that has spread widely around the world, there are 6-8 major subtypes, as well as circulating recombinant forms of a mixture of genes of two or more subtypes. The malleability of the virus and evidence that some forms transmit better and cause more severe disease means that the potential impact on the epidemic of drugs and candidate vaccines is further complicated in developing nations, said Blattner.

"We do not know if a vaccine against one subtype will protect against other subtypes,"said Jorge Flores, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH). "Because of the complexity of the virus and differences in the risk factors among populations it is absolutely critical that any HIV vaccine require multiple trials conducted internationally." He added that coordination will be difficult and will raise extremely complex scientific, logistic and ethical issues. "But, the research effort is growing, maturing and there is more opportunity to grow. Said Flores, " I strongly recommend that scientists here at the meeting jump onto the vaccine development bandwagon if you have not done so yet."

In Baltimore, a partnership of IHV and the University of Maryland School of Medicine Center for Vaccine Development was selected by NIH earlier this year as one of only nine sites of the new HIV Vaccine Trials Network. The selection included $7 million funding that is helping the partnership conduct AIDS vaccine testing research in Baltimore in collaboration with investigators in Trinidad and Tobago and other sites in the Caribbean and, Uganda and Nigeria.

Courtenay Bartholomew of the Medical Research Foundation of Trinidad and Tobago said those nations not yet "twinned" with a major research program could "partner in a triangle with their brothers in Africa and the Caribbean." But he added, "but there is a flaw in partnership," if the gap continues to grow between far more successful AIDS prevention and treatment in developed nations of the North (northern latitudes) and struggling AIDS programs of nations in the South where the epidemic is at its worst and the scientific programs are desperately needed.

Bartholomew, who has directed cooperative research in Trinidad since 1982 with IHV's Blattner, Gallo and others, said the AIDS gap is illustrated by a contrast in the ratio of new infections in 1999 of North America, 44,000 in a population of more than 400 million, to those in the Carribean, 57,000 in a population of only 6 million.

Progressive AIDS programs in Uganda have helped reduce HIV infections from 15 percent of the population six years ago to eight percent last year. But only modest success in Uganda also underscores the lack of African infrastructure in AIDS research and prevention programs, said Phillipa Musoke, lecturer at Uganda's Makerere University and a local leader in combating mother to child HIV transmission. HIV infection rates in African cities average 10 percent, she said, but range from ten to 50 percent in antenatal clinics; some in southern Africa reporting rates of 70 percent.

In Uganda the rate of mother to child transmissions is now 15 percent, down from 30 percent in 1989. Musoke sited a series of studies since showing a reduction of costs of anti-HIV drugs for preventing mother-to-child transmissions since 1994 when AZT was shown to be effective in the United States but far too expensive for Africa. Most recently, researchers found better options. For example, Nevarapine, given as a single intrapartum dose to a mother at the onset of labor and a single dose to the infant with 72 hours can help reduce "vertical" transmission for about $4 a dose, she said.

"Still there are implementation issues. Just because you have a (scientific) regimen does not mean there will be a difference for the African child," said Musoke. In her hospital, there are 20,000 deliveries per year, she said, with 200 to 300 women at a time in antenatal clinics. "It is quite difficult to implement counseling in such limited space and logistics, when only a screen separates one patient from another. A new program this year provided pre-testing for HIV to 3,000 women in groups of 15 at a time. "We only had about 50 percent acceptance of testing and 88 percent of those came back for post-test counseling and willingness to take the drug .

"We have to invest in prevention programs too in Africa where the mothers who are HIV-infected can be given family counseling and planning so they do not become pregnant and also counseling for adolescents and young women and men in reproductive age groups," she added.

Studies show that the longer an HIV-positive woman breast feeds, the higher the chance of transmitting the virus to the child, she said. But breast feeding is encouraged in African cultures for up to two years. The majority of women in Africa are breast fed and a woman can be stigmatized or even physically attacked in some countries when her use of infant feeding formula marks her as HIV positive. Often women leave formula in clinics rather than take a chance at being identified as positive, said Musoke.

Edward Mbidde, director of the Uganda Cancer Center, spoke dramatically of the AIDS gap between the North and South, "Yes we all want prevention or therapeutic vaccine, but these come with a cost to our infrastructure." He added, "We have to show that we can help ourselves. In the past year, there were 4 million new infections in Africa and there was a measly $150 million spent on them. Sadly only ten percent of that came from the governments of Africa. We have a total of 250 million, 25 million are HIV infected. How do we protect the other 225 million from getting infected?"

Mbidde added, the epidemic "has stretched our health sector budgets beyond imagination." Seven of 16 African countries surveyed by the International AIDS Vaccine Initiative spent over two percent of their gross domestic product on treating HIV, but most of the countries had only budgeted three percent of their entire national budgets on three to five percent on the health sector, he said. "The epidemic has caused havoc--life expectancies down, increased orphans, destruction of the very fiber of our society, which is the family." He added that 40 percent of HIV-positive people also contract tuberculosis (TB), further straining the health care sectors in Africa.

"People talk about Uganda as a success story. It is not because we have got antiretroviral therapy (anti-HIV drugs). And no, there is no vaccine to talk about yet." Instead, Mbidde said, Uganda has had success because new national leadership has set up programs to cover a long list of chores to treat people and thus limit some HIV spread: treatment of other sexually transmitted diseases and TB, distribution of condoms, direct observed therapy for HIV cases, better nutrition, and others. "When you add these up, you begin to wonder if the answers work and if they are sustainable.....Well, we have put all this together as an arm of sustainable therapy to give us the success story."

UMBI's Institute of Human Virology was recently selected by the non-profit IAVI for trials of a vaccine in Uganda and Baltimore. Further, IHV has signed a memorandum of understanding with the newly elected government of Nigeria for cooperative HIV research on that country's emerging AIDS epidemic.

Alash'le Abimiku, a visiting research professor at IHV from Nigeria's Jos University Teaching Hospital, said the young average Nigerian population "makes it at high risk for HIV infections. There are 2.6 million infected in the country and a half million children. In areas where the epidemic is most pronounced, you find that infection rates reach to ten to 20 percent." Abimiku said infrastructure in Nigeria is adequate for successful HIV programs--advertisements, condom distribution, blood screening guidelines, integration of HIV programs in the schools, etc.--but previous efforts have failed because of "total lack of coordination." However, the new Nigerian government, has set in motion a "political will," she said, with new programs to build up training of AIDS workers and research.

"What is your advice for nations that do not have a partnership with a major research lab like IHV," and audience member asked Bartholomew of Trinidad. While recognizing a catch-22 dilemma for some hot spots where speed to implement research is of the essence, Bartholomew said that a "track record of previous virus research, data collecting, trials" is necessary for good science. But in addition, such nations should form triangles of cooperation "with their brothers in African and the Caribbean," South to South to North partnerships, he suggested.

"We feel that it is our problem--Africa and the Caribbean, the second highest infection rates are in the Caribbean. Those of us in Africa and the Caribbean who have the expertise to assist in finding a vaccine should collaborate together with the First World countries because, this is our problem mainly--90 percent of the world's infections," said Bartholomew.

"Why is this so important?" he asked. "Because of the high risk of new infections, different clades (strains) of the virus. Immunization of vaccines in the developed world may not predict the response of the vaccine in the developing countries. And it is becoming apparent that different strains of the virus are associated with different infection progression rates of HIV1.

" In terms of the diversity of the HIV viruses, the AIDS epidemic throughout the world has become an extremely complex one compared with when it was first detected in the early 1980's, observed epidemiologist Mauro Schector of the Federal University of Rio de Janeiro, Brazil. He said subtypes of HIV affect how each nation handles its transmission problems, pathogenicity and clinical responses to drug therapies. "How important is the molecular epidemiology of HIV to AIDS programs? It is based on RNA or DNA differences in microbes. For HIV, we need to determine the modes of transmission, sources of infections, and establish principals of exploiting (each type)."

In Brazil, for example, a new subtype b-br has branched from the more common subtype b. He described studies showing that some subtypes progressed much faster in causing AIDS than others. Other studies show that people with some subtypes have poorer responses to therapies. Also, there is some evidence that some subtypes are more transmissible heterosexually than others, he said. In Thailand, Schector said, there are two separate epidemics going on, two subtypes requiring different treatments and studies.

EDITORS NOTES: Statistics from IAVI and UNAIDS were often sited at the IHV conference to reference the need for North-South AIDS research cooperation. Here are a few examples:

• In Africa, AIDS now kills ten times more people a year than war.
• In Botswana, 35.8% of adults are now infected with HIV, while in South Africa, 19.9% are infected, up from 12.9% just two years ago. The adult HIV prevalence rate in Botswana has more than tripled since 1992, when it was an estimated 10%.
• Since the epidemic began, AIDS has created some 12.1 million orphans in Africa. Before AIDS, about 2% of all children in developing countries were orphans. By 1997, the proportion of children with one or both parents dead had skyrocketed to 7% in many African countries.
• In the six countries of southern Africa, AIDS is expected to claim the lives of between 8% and 25% of today's practicing doctors by the year 2005.
• In Zimbabwe, by 1997, the likelihood of a 15-year-old woman dying before the end of her reproductive years quadrupled from around 11% in the early 1980s to over 40% by 1997. More than 2000 Zimbabweans die of AIDS each week.
• In West Africa, relatively less affected, prevalence rates in some countries are creeping up. In Nigeria, by far the most populous country in sub-Saharan Africa, over 2.7 million people are infected with HIV.
• Asia is emerging as a new epicenter of the epidemic. Almost four million people in India are infected.
• There are 15,000 new infections every day, eleven every minute.