PSF Clinic

I have just a few pictures from the medical clinic at PSF...

CDC Guidelines for CVCT

At the end of last year, through the President's Emergency Plan for AIDS Relief (PEPFAR), the U.S. Centers for Disease Control and Prevention (CDC) collaborated with the Rwanda Zambia HIV Research Group (RZHRG), the Liverpool School of Tropical Medicine (LSTM), and other national and international partners to develop the Couples HIV Counseling and Testing (CHCT) Intervention and Training Curriculum. Although the CDC is calling this intervention "CHCT", it is the same thing that RZHRG has developed and is using with the name "CVCT". The curriculum was developed in response to increased demand from field partners for interventions and training that would help them address the complex issues related to HIV counseling and testing with couples, who currently constitute the largest risk group in Africa for HIV transmission. The curriculum can be found online here.

RZHRG in 'The Lancet'

This week, RZHRG published an article in 'The Lancet', one of the oldest and most well-respected, peer-reviewed medical journals, that strongly supports the argument to expand couples' voluntary HIV counseling and testing services. Since the article is quite long, I've only pasted its summary here.

Background Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year.

Methods We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001–02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year.

Findings We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55·1% to 92·7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60·3% to 94·2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35·7% to 60·3% of heterosexually transmitted HIV infections that would otherwise occur.

Interpretation Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.

Funding US National Institute of Mental Health, National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, Fogarty AIDS International Training and Research Program, Emory Center for AIDS Research, and the International AIDS Vaccine Initiative.

National HIV Testing Day

Do you know your HIV status? I don't mean, "do you think you know your HIV status?" or "are you pretty sure you know your HIV status?" I mean, "have you been tested and are you sure you know your HIV status?"

The CDC estimates that approximately 25% of American infected with HIV are unaware of their status. That's 180,000 to 280,000 people. And it's not just black women or homosexual men or poor African or Hispanic immigrants; HIV isn't a disease that only affects a particular group. Did you know that while the South represents a little more than one-third of the U.S. population, it accounts for 40% of people who have AIDS and 46% of new cases?

If you don't know your HIV status, you can visit http://www.hivtest.org/index.cfm to find a testing site near you. There are a number of locations that offer free, confidential testing. In Greenville, one is AID Upstate and, in Atlanta, one is AID Atlanta.

To quote this year's theme - "Take the test. Take control."

Pictures of ZEHRP

This week I took a few pictures around ZEHRP that I wanted to share, and I realized that I never did the same in Kigali, so I'll be sure to take some pictures there when I return.

ZEHRP has two sites, just like PSF, one for clinical trials and one for other studies. The former is referred to as "IAVI", after its major funder, and the latter is referred to as "main site". Unlike PSF, ZEHRP's main site is consolidated within a single compound that contains the administrative building, lab, clinic, etc.

This is our administrative building, which houses the administration department, data department and offices for several others.
As I mentioned, the data department is housed within the administrative building. (I know it looks like a mess in these pictures; I've been trying to get things in better order!)
The main site lab is just to the right of the administrative building.And, finally, this is the clinic building, which is just behind the administrative building. The tented area in front is where lunch is served every day at the project. The second picture is the back of the building, just outside the phlebotomy room.

HIV tests and ARVs

I recently discovered two interesting cases among individuals enrolled in studies at PSF. I was working on a query for a publication and noticed that there were two individuals who were HIV-negative but reported a date on which they began anti-retroviral (ARV) therapy, the treatment used for individuals who are HIV-positive. I assumed an error had been made during data entry, but, as I investigated these cases further, I became really concerned.

The first individual tested positive at PSF's couples' voluntary counseling and testing center on two out of three rapid tests, which, according to the national algorithm for HIV-testing, identifies this individual as HIV-positive. (It is not at all uncommon for individuals to have different results on different tests.) For several months, this individual continued to test positive. When a CD4 count (the test used as a diagnostic for HIV treatment) was ordered, it was found to be very low, so the individual began ARV treatment. At this point there was no indication that something was strange, no red flag that something was wrong, no indication that a protocol that had been followed incorrectly. But then, the individual began to test HIV-negative, and with more sophisticated laboratory tests, it was resolved that the individual was indeed HIV-negative.

The second individual had a similar testing history.

Were these individuals were cured by ARV therapy? No. Had an error been made in their lab tests or results? No.

Both of these cases were what we call "seroreverters", individuals who test HIV-positive for some period of time before reverting to HIV-negative test results. It is a curious situation that is not yet well-understood, but false-positive HIV test results are not uncommon. In fact, it is fairly common for HIV-negative individuals to test positive on a single rapid test, somewhat less common to test positive on multiple tests. Yet there are individuals who have separate infections or cross-reacting viruses that cause positive results on HIV tests even though the individuals are not actually infected with HIV. When the individuals' immune systems later clear this cross-reacting virus, they revert to negative HIV test results. This is what happened in both of these cases.

As for these individuals' low CD4 counts that indicated a need to begin ARV therapy, it is purely coincidence. Some individuals just have naturally low CD4 counts.

Even though there have only been two individuals for which this has happened at PSF, I feel like the implications of these facts are significant.

While we follow a strict testing algorithm at PSF and ZEHRP that involves diagnosis based on three rapid tests followed by more sensitive ELISA tests in cases of discrepant results, we have seen in Rwanda that most health centers use only a single rapid test for HIV diagnosis. Nurses and counselors report that there are just too many clients and too little time to do even one confirmatory test. Yet the single rapid test that they use is one that has shown a particularly high number of false positive results at PSF. While we at PSF can identify these false positive results by use of confirmatory tests, if the health centers are not using any confirmatory tests, then how many HIV-negative individuals are receiving positive diagnoses? The numbers must be high. And how many of these then have naturally low CD4 counts?

A whole series of questions and concerns then fills my mind - How many individuals are on ARVs who are actually HIV-negative? What effects do intense ARVs have on the bodies of individuals who are not infected with HIV? What are the economic implications when expensive ARVs are wasted on individuals who are actually HIV-negative? How does providing ARV therapy to HIV-negative individuals contribute to drug resistance if these individuals are later exposed to the HIV virus? What effect does this have on the community's understanding of HIV and ARV therapy when these individuals later receive HIV-negative results? Does the community believe they have been cured or do they believe HIV is a myth made up by the Western world?

About ZEHRP

I realized that some of you may be wondering about my sudden move to Zambia, or perhaps why the organization for which I work has projects in Rwanda and Zambia, of all countries.

As I've mentioned previously (see 'About RZHRG and PSF' posted in September 2007), Projet San Francisco (PSF), where I was working in Kigali, Rwanda, was founded in 1986. Its sister project in Lusaka, Zambia, was later established in 1994, when Dr. Allen, the founder of the organization, and many of her staff fled to Zambia for safety during the Rwandan genocide. Rather than give up their work, those who made it to Zambia established a sister project here that is now known as the Zambia Emory HIV Research Group (ZEHRP).

Since 1994, the project has offered couples' voluntary counseling and testing (CVCT) services to over 20,000 couples in Lusaka. Among these 20,000 couples, over 13,000 HIV-infections have been diagnosed and 6,000 syphilis infections have been treated. Like PSF, ZERHP has couples' voluntary counseling and testing facilities, two medical clinics, laboratories and a pharmacy. The project employs around 150 Zambian medical and support staff and 5 to 10 expatriate staff.

The most recent news for ZEHRP was the awarding of a large grant from the Centers for Disease Control and Prevention (CDC) to expand CVCT services to a greater number of clinics in Lusaka and throughout the southern province of Zambia. With this grant, CVCT services have expanded over the last couple months from three fixed sites in Lusaka to more than twelve district health centers and other sites in the region. As exciting as this expansion has been and as many people as are benefiting from the new CVCT services, it's created lots and lots of work for ZEHRP staff, which is the reason I've come down here from Kigali for a couple months. Hopefully I'll be able to help set up and organize some of the systems for this expansion and will then be able to return to Kigali to help do the same as we look forward to expansion there as well.

Need for a vaccine

Another article was published this week that only further supports the need for an HIV vaccine.

UN: New HIV infections outpaces drug treatment
by: John Heilprin

Despite a stepped up global battle against AIDS, the numbers of people newly infected with HIV are far and away outpacing the numbers beginning antiretroviral drug treatments, U.N. officials said Monday.

Secretary-General Ban Ki-moon, opening several days of U.N. debate on AIDS prevention, told world leaders that 2.5 million people became infected with HIV last year compared with 1 million who started using important antiretroviral drugs.

"Unless greater and swifter advances are made in reaching those who need essential services, the epidemic's burden on households, communities and societies will continue to mount," Ban said.

Some 2.1 million people died of AIDS last year and at least 33 million people world wide have the HIV infection, according to U.N. figures.

In addition, people with weakened immune systems from HIV are up to 50 times more likely to develop tuberculosis, U.N. officials say.

"We cannot separate the fight against HIV/AIDS from the fight against TB," said General Assembly President Srgjan Kerim, who will preside over a two-day meeting on AIDS starting Tuesday.

Former President Bill Clinton pointed out ramifications that rising oil prices have on battling the disease.

"This oil price spike has taken away 100 percent of the value of foreign aid and debt relief to very many countries," he told the U.N. "It has dramatically increased the cost of producing food, and it has increased therefore the number of people who are at risk of these diseases."

Dr. Peter Piot, executive director of UNAIDS, said 2 million people were getting antiretroviral drugs in Africa.

Antiretroviral drugs have made HIV a manageable illness for many patients and prolonged their lives beyond what once seemed possible.

The U.N.-backed Global Fund to Fight AIDS Tuberculosis and Malaria announced Monday it helped 1.75 million get antiretroviral treatment — a 59 percent increase over last year.

But slightly more than two-thirds of people with HIV globally are not getting any such treatment, according to U.N. figures.

Vaccine search is vital

In response to the article from the AIDS Healthcare Foundation (see 'Enough is enough'), several leaders in the HIV/AIDS research community, including Dr. Eric Hunger, who works closely with Projet San Francisco and our field sites in Zambia, published another article in the Atlanta Journal-Constitution.

Vaccine search is vital in HIV/AIDS arsenal
by: Mark Mulligan, James Curran, Eric Hunter, Carlos del Rio

In an April 7 opinion column, Drs. Homayoon Khanlou and Michael Weinstein of the AIDS Healthcare Foundation made several statements with which we strongly disagree ("The best way to fight AIDS," @issue).

Global access to HIV/AIDS prevention, testing and antiretroviral treatment is inadequate, and increased funding is needed. We strongly disagree, however, with the suggestion by Khanlou and Weinstein that the best way to fight AIDS is to end government funding for HIV vaccine research and to redirect those funds to prevention, testing and treatment.

History teaches that it is wrong to take an either/or approach to the provision of health care services and vaccine research. In the U.S., despite sustained prevention efforts and widespread use of antiretroviral treatment, 40,000 people are infected with HIV each year. Globally, more than 33 million are infected with HIV. UNAIDS estimates that in 2007, 2.5 million people became infected and 2.1 million deaths occurred from AIDS. Each day, 6,800 persons become infected and 5,700 die from AIDS.

Despite impressive initial steps in antiretroviral rollout in developing countries - due to the U.S. President's Emergency Plan for AIDS Relief and other programs - only a fraction of those in need of treatment have received it. The number of HIV-infected persons being treated with antiretroviral drugs in less developed countries is fewer than either the number of deaths or new infections in a single year. Since therapy does not cure HIV, every new infection represents a person who ultimately must be treated for life.

More attention to HIV prevention is urgently needed, and quality education, counseling and testing and other services are warranted. Even when these are fully utilized, it is likely that the number of new infections will remain high.

New and better HIV prevention interventions are clearly required. Historically, vaccines have been the most effective weapons against infectious diseases. The world desperately needs a vaccine for HIV prevention. Khanlou and Weinstein incorrectly stated that there is no precedent for a vaccine against the retroviruses, the viral family to which HIV belongs. Veterinarians administer a vaccine for protection against the leading viral killer of cats, a retrovirus called feline leukemia virus.

Research is a time-consuming process of trial and error, hypothesis generation and testing, refinement and retesting. Vaccine development historically has taken decades, with each interim result contributing new knowledge. The recent clinical trial called the Step Study tested one candidate HIV vaccine. It was disappointing that the vaccine did not protect those who received it. But the study was successful in that it was well-executed and efficiently provided an answer, albeit not the desired one.

History provides powerful lessons. The virus that causes polio was discovered in the 1930s. Initial vaccines tested in the 1930s were ineffective. In the 1940s and early 1950s, summertime polio epidemics caused fear and panic in industrialized countries. Fortunately, vaccine research continued despite initial failures. Progress was based on incremental scientific advances such as the discovery in 1949 by John Enders and his colleagues of how to grow the polio virus in the laboratory. Six years later Jonas Salk's inactivated, injected polio vaccine became available.

By 1957, the number of new polio cases annually had fallen by 90 percent, and over time - thanks to sustained scientific effort even in the face of early failures - the iron lung became a museum relic. Imagine if the polio vaccine developers had given up after 20 years, or after a couple of failed vaccine trials.

The National Institutes of Health Summit on HIV Vaccine Research and Development was held in Washington on March 25, led by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. At this meeting of vaccine and AIDS scientists, care providers and community members, Fauci unequivocally expressed the government's commitment to sustained HIV vaccine research. Based on the input of the summit participants, NIAID will review the balance of resources devoted to HIV/AIDS research and make adjustments to match the state of the science.

Funding for HIV vaccine research must not be cut. If anything, it needs to be increased. Persistence, sustained scientific effort and increased collaboration will drive the quest for an HIV vaccine forward - just as they did for the polio vaccine.

Mark Mulligan is executive director of the Hope Clinic of the Emory Vaccine Center. James Curran is dean of the Rollins School of Public Health and co-director of the Center for AIDS Research at Emory University. Eric Hunter is a professor of pathology and laboratory medicine at Emory and co-director of Emory's Center for AIDS Research. Carlos del Rio is a professor of medicine at Emory and co-director of the university's Center for AIDS Research.

Empty office

Usually the rains don't come until the afternoon, but, when I woke up this morning, they had come early, in full force. The sound of the rain pouring on the tile roof made it difficult to get out of bed and even harder to leave my front doorway and walk to the office. Even with my raincoat, I was pretty well soaked by the time I arrived at the office a few minutes after eight o'clock. I was nervous that I would be the last to arrive, but when I opened the door, my office, which is normally full of at least eight data techs, a few counselors, several nurses and a couple lab techs, I saw no one. The office was completely empty, and it was obvious that no one had been there yet today. After a few minutes, one of my expatriate coworkers walked in. She was confused as I was, and we began to wonder if perhaps today was a holiday that had not been announced (amazingly, this is not a completely uncommon occurrence). Since there was no one to ask for clarification, and since even if it were a holiday, we were both already in the office, we began to work. Two hours later, the rains stopped, and approximately half an hour after that, people began to show up for work. At that point it became clear. I had forgotten that no one wants to get wet on their walk to the bus or the moto, so when it rains in the mornings, no one comes to work until after the rains have stopped. The rain is actually a valid excuse to come to work two and a half hours late, and I really can't argue with that.

Update on failed vaccine

More news came out this week about Merck's failed HIV vaccine trial. Below is an article from TIME magazine that was published today.

Assessing a Failed AIDS Vaccine
by: Alice Park

After 20 years of defeat, it appeared that science may have finally developed a viable vaccine against AIDS. Merck's new drug, V520, was being tested in a huge clinical trial, involving 3,000 people in 15 cities, and it was widely considered the most promising new candidate in the field. But last September, when Merck analyzed its initial trial data, it found that the vaccine had failed — and failed miserably. On Wednesday, the company issued its first report on the V520 trials, revealing that the drug did not protect against HIV, and more disturbingly, actually increased some people's susceptibility to the virus. "I don't think anyone imagined the results would be so definitively negative so quickly," says Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health.

V520 may have failed, but somewhere in the details of the drug's nonsuccess, scientists hope to find insight into what will make future vaccines work. After all, V520 is just one of about 50 experimental HIV vaccines that are currently being tested in clinical trials, and almost all of them are designed to function the same way. While most vaccines expose the body to weakened or killed viruses, or pieces of them, to boost production of antibodies — proteins that recognize invading cells and flag them for destruction — that tack alone was too feeble to fend off HIV. The new class of vaccines, including V520, takes a more direct route: They trigger cell-mediated immunity, which marshals killer T cells that both recognize and destroy viruses and bacteria, and can lead to a more robust, specific and longer-lived immune defense.

It's not yet clear why V520 didn't work, but one theory involves its vector, or delivery vehicle. Like almost every other AIDS vaccine in development, Merck's drug used the common cold virus to transport its payload — three synthetic HIV genes — into the body's cells. What makes the adenovirus ideal for the task is precisely the reason colds make us so miserable — once inside a host, the cold virus infects cells and starts to replicate quickly. The down side to that efficiency, however, is that cold viruses are so common that most people have developed a certain level of tolerance to them; if the adenovirus fails to excite the immune system, then any bugs piggybacked on the virus, such as HIV genes, will also slip past immune defenses. That's exactly what appears to have happened in the Merck trial: People with the highest pre-existing immunity to the common cold also had the highest rates of infection with HIV.

"It could be due to chance, or to differences in the populations we studied, or to something related to the vaccine itself," says Dr. Keith Gottesdiener, vice president of Vaccine and Infectious Disease Clinical Research at Merck. "The 'why' is still not well known."

Researchers have already set about trying to figure it out. "We have to remember that Merck's was a single product testing a vaccine concept, which is that T cell immunity can protect against HIV infection," says Nabel. "And we know there are other ways to stimulate T cell immunity." Nabel is ready to test one such method, a vaccine similar to Merck's that uses different HIV genes and a "prime-boost" approach that involves two injections spaced a few months apart, instead of one shot, to maximize the stimulation of the body's T cells. Other researchers, like Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York City and the recipient of a $25 million grant from the Gates Foundation to study novel vaccine strategies, think that the cold virus isn't the best way to deliver HIV. Ho is exploring the possibility that a different vector, such as the chicken pox virus, or perhaps no vector at all — simply injecting snippets of naked HIV DNA — could yield stronger immune responses.

At the International AIDS Vaccine Initiative (IAVI), a non-profit group of public and private partners focused on funding and accelerating AIDS vaccine research, scientists are studying the use of crippled, live strains of HIV — based on the success of other such live attenuated vaccines against polio and measles — which they think might be critical to waking up the right immune system defenses. "There is something magical about the replicating virus, because it has virtually its entire genome," says Dr. Seth Berkley, president of IAVI. His group is also investigating ways to stimulate so-called neutralizing antibodies, a special class of antibodies that appear to be able to defuse HIV.

Despite the ongoing study, experts argue that none of it will succeed without some basic changes in the way it's conducted. Most research occurs in isolation; there's little coordination among labs and no network through which data can be shared, making it difficult for scientists to learn from each other's missteps. Worse, it takes years to get regulatory approval to start a human trial for a new vaccine — not to mention enrolling the volunteers and training the right personnel — so, by the time experiments get underway, the science around which the vaccine was built has long since become outdated. "The trials are not informing science at the moment," says Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, an alliance of independent organizations dedicated to accelerating HIV vaccine research. "Science — and vaccine development — is an iterative process, except that in HIV vaccine research, there isn't a lot of iteration going on."

The Enterprise, which was founded in 2005, intends to change that. With funding from the Gates Foundation, Wellcome Trust, National Institutes of Health and the European Union, it will serve as a hub for guiding worldwide HIV vaccine research. “We want to ensure that the trials are done faster, better and smarter,” says Bernstein. And hopefully, with more success.

Projet San Francisco

I’ve recently realized that even though I’ve been writing on a regular basis, I haven’t really explained Projet San Francisco (PSF) or the work that I do on a daily basis. I’ll start today with the project, which is easiest to explain by breaking it into three parts.

The first aspect of the project is couples’ voluntary counseling and testing (CVCT). PSF operates three centers throughout Kigali that provide services to married and cohabiting couples. The centers are open three days per week for couples to come to receive information, testing and counseling for HIV and syphilis. The project promotes these services in a number of ways. Sometimes radio announcements and billboards are used, but our predominant means of promotion involves recruiting community leaders (such as ministers, civic leaders, public officials, teachers and others) to publicize our services within the community and distribute information and invitations to couples interested in our services. I’ve already described what happens at CVCT in a posting on 13 September 2007, so I won’t repeat myself, but I will mention that lately we’ve been seeing approximately one hundred couples each week.

The second aspect of the project – observational studies – stems from CVCT. Of the couples who are tested at CVCT, couples who are discordant, meaning one partner is HIV-positive and one is HIV-negative, and who meet certain eligibility criteria are invited to join our study of heterosexual transmission of HIV, which we refer to as the HT study. This is an observational study to understand the behavioral, virologic, immunologic and immunogenetic correlates of HIV transmission, so these couples come to our main site every one to three months for follow-up and testing. We also have an observational study of a cohort of 85 long-term nonprogressors, many of whom have been HIV-positive for twenty years. These women are studied to identify why they remain healthy despite HIV infection and to analyze host and receiver genetics related to the progression of HIV. They come to the clinic every three months. All observational study participants receive some benefits for their time and effort. At each visit they are reimbursed for their transportation cost and are given lunch. They are also welcome to receive reproductive health care from PSF and are given mutuelle cards so that they are able to obtain free health care at their local clinic. Currently we have approximately 900 individuals in these observational studies, the largest cohort of discordant couples in the world (the second largest is our project’s cohort in Zambia), and we see forty to fifty individuals at the clinic each morning.

The third aspect consists of more specialized research, currently focusing vaccine feasibility studies and clinical trials. Participants in these studies are usually recruited from the HT study. Some recent and ongoing studies include a clinical trial to evaluate whether HIV-transmission could be reduced by suppressive treatment of genital herpes with acyclovir, the establishment of reference ranges for lab results to identify adverse events in a trial, studies of disease progression in newly-infected individuals and follow up of long term nonprogressors (a different study from the one I mentioned above). We were prepared to begin a clinical trial of an HIV vaccine this month, but with the disappointing results from the Merck trial, it’s been postponed.

I’ll try to write soon about my role within all of this, but let me know if you have any questions so far. Below is a picture of one of the project buildings and the road on which most of our offices are located.

Vaccine research nightmare

I mentioned a few weeks ago that an HIV-vaccine trial by Merck had been canceled, but now more details are coming out about the results of the trial, and it really doesn't look good. It seems the vaccine actually put people at greater risk of getting HIV rather than decreasing their risk. The results from the trials in North America won't be available for a couple more weeks, but if they show the same results, this has several serious implications: (1) the most obvious implication is that now all the people who participated in the trial and received the vaccine are now at greater risk of getting HIV, (2) when another vaccine is ready to be tested, it will be much harder to recruit participants to be in the trial, (3) this may be the end of the road for a number of other vaccine candidates because many of the vaccines that are in advanced stages of research have the same basic mechanism as the Merck vaccine, and (4) we most likely will not be going through with our vaccine trial here at PSF. Here's the article from the Washington Post.

Warning is sent to AIDS vaccine volunteers
by: Craig Timberg

South African AIDS researchers have begun warning hundreds of volunteers that a highly touted experimental vaccine they received in recent months might make them more, not less, likely to contract HIV in the midst of one of the world's most rampant epidemics.

The move stems from the discovery last month that an AIDS vaccine developed by Merck & Co. might have led to more infections than it averted among study subjects in the United States and other countries. Among those who received at least two doses of the vaccine, 19 contracted HIV compared with 11 of those given placebos.

Researchers shut down the trial on the grounds that the vaccine was proving ineffective, but the surge in infection among vaccinated volunteers prompted intense scientific debate and anxiety among researchers. The failure of the Merck vaccine is the latest in a series of disappointing results for research projects aimed at curbing AIDS.

"This is my worst nightmare," said Glenda Gray, the lead South Africa investigator for the vaccine study. "I haven't slept for days. I have a headache. I'm ready to resign from trials for the rest of my life."

Researchers in Soweto, Cape Town, Durban and two other sites began contacting South Africa's 801 trial participants on Tuesday, mainly by cellphone text message. The goal is to tell each one individually whether they had received a placebo or the vaccine, a process called "unblinding" the trial. Researchers are telling the roughly half who received the vaccine that it might have increased their risk of contracting HIV.

"It's quite shocking," said Nelly Nonoise, 26, who had received three injections of the vaccine in her left shoulder.

She added, "I probably wouldn't have joined the study knowing there's a risk."

Another participant, Nonhlanhla Nqakala, 22, said she thought the text message urging her to visit the vaccine test site meant she had tested positive for HIV. Her brother and a close friend had the disease and died, she said.

Nqakala said she was relieved when a doctor explained that she was not infected, but the news of a possible problem with the vaccine -- she had received three doses, not placebos -- left her distressed. "I thought the trial would help us find a cure for HIV," she said.

Merck developed the vaccine in conjunction with the U.S. National Institutes of Health, and until September's announcement, researchers worldwide considered it the most promising candidate yet in a multibillion-dollar quest for an AIDS vaccine dating to the 1980s.

Scientists crafted the vaccine by genetically altering a common virus to include elements of HIV. They hoped that it would trigger an immune response that would make recipients less likely to contract HIV, or at least delay the onset of full-blown AIDS.

The vaccine could not have caused infection, researchers say, but it could have caused immunological changes that made it easier for the virus to take hold during a later exposure.

The Merck vaccine trials took place in 15 cities in the United States, including Boston, Los Angeles and New York, and three in Canada. There were also sites in Peru, Brazil, Australia, Haiti, the Dominican Republic and Jamaica. Those trials began in December 2004 and included 3,000 participants, mostly gay men.

In South Africa -- where an estimated 5.5 million people are infected with HIV, more than in any other country -- the study used the same vaccine but was administered separately. The trial here started later, with the first injections this year, and had its own ethics oversight board. Most of the subjects were heterosexual.

The ethics oversight board in the United States, which monitored the trial everywhere but in South Africa, has not decided whether to tell participants if they received the placebo or the vaccine, said Mark Feinberg, vice president for medical affairs and policy for Merck.

Continuing research could be compromised, he said, if participants were told immediately whether they received the placebo or the vaccine. Vaccine researchers are scheduled to meet in Seattle on Nov. 7.

"Given the complexity of the issue, we feel the best conclusions will be reached when all the data are analyzed in their entirety," Feinberg said from Atlanta, where he was traveling.

He added that individual participants who want to know whether they received the vaccine will be told. Researchers also are counseling all study participants that the vaccine may have increased HIV risk for those who received it.

Other AIDS studies also have had unexpected results. Trials of two vaginal microbicide gels to prevent HIV led to more infections among those using the products instead of placebos. A massive study in Zimbabwe of the ability of HIV counseling and testing to prevent the spread of the epidemic found more infections among those with expanded access to testing.

Seroconversions

At work today, we had our third seroconversion in two weeks, meaning that, in only fourteen days, three of our study participants who were initially HIV-negative have been infected with the virus. That’s three more individuals added to the forty million already living with HIV/AIDS. Three more who will ultimately die from a disease that has been around for twenty years and yet we still can’t find a way to prevent or cure it. These three individuals weren’t infected because they were part of a classic ‘high risk’ group such as sex workers or injecting drug users. And they weren’t uneducated about HIV; on the contrary, they received counseling and education from the project at least once every three months. Their only downfall was being married to or cohabiting with someone who was HIV-positive. So if these individuals weren’t participating in ‘high risk’ behavior and they weren’t unaware of the disease, how much, then, are our prevention strategies really doing? In the world of HIV, we continue to preach the ABCs, but are those interventions really appropriate for the largest risk group in the world? Abstinence promotion isn’t exactly an appropriate intervention when you’re working with married and cohabiting couples. Being faithful is a suitable message, but it does nothing for discordant couples where one partner is already HIV-positive. Condom use is the only other strategy, and while it has been proven effective, it isn’t always an option. What about those with religious beliefs which prohibit contraceptive use? Or those in relationships with partners who refuse to use them? Or those who want to have children? Maybe the ABCs are the best option we have right now, but if the best we have doesn’t work for the largest risk group in the world, then what do we really have?

Global HIV/AIDS timeline

The Kaiser Family Foundation has put together an interactive timeline that provides information on key HIV/AIDS-related events since 1981. Also, if you look just below the timeline, there is an estimate of the number of people living with HIV/AIDS for each year. If you're interested, visit http://www.kff.org/hivaids/timeline/hivtimeline.cfm.

CVCT

Before I begin my own work at Projet San Francisco (PSF), I will complete rotations through each of the departments and aspects of the project. I began today with the Couples’ Voluntary Counseling and Testing (CVCT) centers.

PSF operates three CVCT centers that are spread throughout Kigali. When couples arrive at one of the three PSF sites in town for CVCT, they first go through verification to ensure that they are truly a cohabiting couple (a later requirement for participation in our studies). They then participate in a group session, which I observed at Gitega (the CVCT site located at our main site), where ten couples were present for testing. The group first participates in an information session that covers topics including background information on PSF, the differences between HIV and AIDS, possible test results (both partners positive, both negative, one positive and one negative), how to prevent transmission (including how to use a condom), and various other topics such as prevention of mother to child transmission (PMTCT) and sexually transmitted infections. After each topic is presented in a video, a senior nurse counselor highlights important points and answers any questions. The group then watches a video about informed consent. Since we are a research institution, all couples must sign a document that states their consent to participate before they are even counseled.

After the group sessions, each couple is seen separately for pre-test counseling. For this session, I went to the PSF site at Gatsata, which is about a 15 minute drive away. I sat in on two pre-test counseling sessions, during which a nurse counselor makes sure the couple understands testing and is prepared for whatever results they may receive. Although these sessions (like all others) are conducted in Kinyarwanda (the local language here), I could tell that the nurse counselor is very thorough and very sensitive to the couples. After pre-test counseling, the couples are sent to the lab, where blood is drawn for testing. They then return to the group room, where they receive lunch while waiting for their results. I joined the lab technicians to centrifuge samples and run rapid tests for HIV and syphilis. We then prepared the results for each couple, sealing each person’s results in a separate envelope. After lunch, the couples return to nurse counselors for post-test counseling and to receive their results. Before giving results to the couple, the nurse counselor was careful to make sure that couples again understood and were prepared for the results they were about to receive. Then each individual was handed his or her envelope, which he/she opened for his/her results. Both couples I joined for CVCT were concordant negative, meaning both partners received negative results from their HIV tests. And both were so thankful – one couple even jumped to their feet and hugged the nurse counselor and I after reading their results. I was thankful too; it’s going to be really difficult to be in the room with a couple when at least one partner is positive. The nurse counselor again made sure the couple understood the results after reading them and, for the two discordant negative couples, discussed the importance of fidelity in order to maintain their negative status.

After all the couples were counseled and dismissed, I joined the nurse counselors and lab technicians for lunch. We had a truly hearty lunch of rice, beans, meat (I couldn’t tell you what kind, but it was good), and cassava. I don’t know if I can eat that large and hearty of a meal every day, but it was a good introduction to Rwandan cuisine.

At the end of the day, I left the site and stopped by the third PSF site at Kicukiro to check on the day’s results there.

It was a good first day, but very busy and very full. There's a lot of work to be done.

About RZHRG and PSF

(Note: This post is copied from the RZHRG website with only a few updates and a little editing from me. If you still have questions about RZHRG or PSF after reading this, let me know, and I'll be happy to answer them!)

About RZHRG

The principal research objectives of RZHRG are to uncover factors relating to HIV risk and transmission, to gain a better understanding of how to prevent the spread of HIV and to improve the quality of life among HIV infected African adults. To achieve these goals, the project sites in Kigali, Rwanda, and Lusaka, Ndola, and Kitwe, Zambia, operate couples’ voluntary counseling and testing (CVCT) centers where couples receive education about HIV/AIDS, pre- and post-test counseling and free testing for HIV. Couples eligible for ongoing studies are invited to participate in follow-up research and provided with free outpatient reproductive and general health care.

Until an effective HIV vaccine is found, prevention of new infections in African adults must rely on behavioral interventions. RZHRG and its many collaborators first published the beneficial impact of CVCT on risk reduction in African couples in 1991 but widespread implementation of VCT was delayed 10 years by a variety of controversies. There is now consensus that VCT is an effective prevention strategy, and that the impact of this strategy is greatest in the world’s largest risk group: African cohabiting couples.

The RZHRG same-day couples’ VCT programs were intended to be a screening tool to identify HIV discordant heterosexual couples (one partner HIV positive and the other HIV negative) for prevention, pathogenesis and vaccine evaluation research. In the process, RZHRG’s research sites in Rwanda and Zambia have accrued the largest couples’ VCT cohorts in the world. RZHRG continues to research the best ways to deliver CVCT and to provide leadership in the dissemination of best practices in VCT for couples. RZHRG’s researchers have led by example as they have developed and tested interventions and, as a result of their findings, have directly impacted public health practice. It has also been the privilege of Dr. Allen and the rest of the RZHRG team to develop collaborative relationships with colleagues from all over the world, to provide internships to more than 85 US and European trainees and to bring 19 African colleagues through Masters in Public Health degree training in the United States and England. Although the majority of the project’s research has been sponsored by the U.S. National Institutes of Health, over the years RZHRG has also been funded by a dozen other international, bilateral and non-governmental development and research organizations.

About PSF

Since 1986, Projet San Francisco (PSF) has been conducting HIV/AIDS research, as well as providing clinical care and counseling for HIV-infected persons, in Rwanda. PSF works closely with the Centre Hospitalier Kigali (CHK), the National HIV/AIDS Reference Laboratory and the Ministry of Health’s Treatment and Research on AIDS Center (TRAC) to improve clinical care available for HIV-infected persons. PSF runs three couples’ voluntary counseling and testing facilities in Kigali as well as a medical clinic, laboratory and pharmacy. The project employs over 150 Rwandan medical and support staff and 5 to 10 expatriate interns and project coordinators. With CHK and TRAC across the street from PSF, physicians from the CHK rotate every afternoon in the PSF outpatient clinic. This ensures continuity of care when hospitalization is required.

In addition to providing clinical care since 1986 for 95 long-term survivors of the project’s original HIV-positive cohort, PSF also provides HIV voluntary counseling and testing for couples, with over 17,000 couples tested, 8,000 people provided with screening for sexually transmitted infections and 940 HIV discordant couples receiving general outpatient care at the PSF clinic.

The challenge ahead

On my flight from Amsterdam to Nairobi, I sat in the window seat next to two Kenyan businessmen living in the U.S. They were returning to Nairobi so that one could run for a seat in the senate. (I still don’t quite understand, but that’s not the point of my story.) While we were talking over dinner, I explained that I was in Africa to work in HIV research, and one of the men began to tell me about a book he read that explains the origin of AIDS. He told me all about the lab in California that created the disease, the men who came to Africa to test it on monkeys and those who later began testing it on humans. I was shocked. How could these men – these well-educated men who have lived abroad for over twenty years – believe such a myth? I of course did my best to explain to them the true origin of HIV/AIDS, but I don’t know that either of them was convinced. I’m sure they still believe the disease was invented by a group of scientists in California. The previously light conversation turned into a serious reality check for me. It was a reminder of the challenges to come working with a disease that is so seriously misunderstood.

The misconceptions and myths surrounding HIV/AIDS are almost endless. Some, such as the idea that HIV/AIDS in Africa is a conspiracy from the U.S. government or that having sex with a virgin can cure HIV/AIDS, seem almost absurd. It's easy to blame these misunderstandings on a lack of education or a lack of understanding. But the myths surrounding HIV/AIDS are just as common in developed countries like the U.S. as they are anywhere else in the world. Check out http://www.amsa.org/global/aids/aidsfacts.cfm for a summary of ten common myths from the perspective of the developed world.