Bringing Vaccines to Soweto: An Interview with Glenda Gray

In 2002, South African pediatrician and AIDS crusader Glenda Gray won the 2002 Nelson Mandela award for Health and Human Rights.

A tireless crusader for people with HIV and AIDS, Gray, colleague James McIntyre and their teams at Chris Hani Baragwanath Hospital in Soweto, South Africa, have spent over a decade developing one of Africa’s premiere clinical trials sites. Gray’s group has led the field in testing interventions to prevent mother-to-child transmission, including the South African Intrapartum Nevirapine Study (SAINT) and several other large-scale trials. Her research has also provided in-depth documentation of women’s life experiences, including early age of first sexual experience and high levels of sexual abuse. In recent years, Gray and her colleagues have entered the HIV vaccine field, and begun preparing for Phase I vaccine trials, as well as conducting community education and outreach for an eventual Phase III trial. Recently, Gray talked with IAVI Report Senior Writer Emily Bass about bringing vaccine research to Soweto.


Let’s start with an update on the status of the vaccine trials you’re involved in.

We have submitted three trials to the Medicines Control Council [MCC] for approval. One is for a clade C VEE [Venezuelan Equine Encephalitis] vaccine. Another is the Oxford/university of Nairobi/IAVI clade A MVA [Modified Vaccinia Ankara]. The third one is the Merck trial. The MCC Ethics Committee has put a hold on approval of all vaccine trials, pending a consensus on what to do about long-term treatment of people who become infected during trials.

Who will be involved in reaching that consensus?

It’s not entirely clear. What we’re hoping is that the national government, together with the National Ethics Committee, will convene a meeting [possibly in early- to mid-February 2003] to raise issues and concerns and then get to some kind of consensus about what is fair and reasonable. After that, hopefully they’ll lift the hold on approvals.

The Soweto vaccine research team has a strong community advisory board and an ongoing “pre-trial” protocol that screens and enrolls HIV-negative individuals as potential Phase I trial volunteers. How are these groups coping with the Ôhurry-up-and-wait’ phenomenon?

It’s difficult to know how to pace ourselves. People like to volunteer in Soweto, and we’ve always had an amazing response to our outreach efforts. We now have about 50 people ready to go into a vaccine trial. We’ve gone through at least six months of preparedness and we don’t know whether to rev up or slow down. We want to go full throttle, but we’re scared of having huge numbers of people in a holding pattern. What can you do to keep the volunteers involved?

A good strategy is to use them to go out to schools or community groups, and say, “Guess what, I’m going to volunteer for a vaccine trial.”

The national government in South Africa has not taken steps so far to provide ARVs. So why raise the issue in this context?

It’s intriguing and surprising. At a national government level, there’s ambiguity around the provision of antiretroviral therapy. At the same time, the MCC and the IRBs [Institutional Review Boards] are talking about requiring that research trials treat volunteers who have breakthrough infections with antiretrovirals. So there is a discrepancy and a disconnect.

What do you think should be done?

My first premise is that everybody who is HIV-infected and has CD4 counts below 200 deserves and should get access to treatment. There are other logistic issues, however, because we know that CD4 counts may not drop below 200 until five or 10 years after infection. And researchers can’t honestly say, “I guarantee that I will be here for the next 10, 20 years [providing treatment],” because they don’t know what’s going to happen on that time scale.

There should be a bigger, more sustainable mechanism [than individual researchers or trials] to manage and handle the care of people who need therapy. Now, if the government provided antiretroviral therapy for all people who needed it, the problem would be moot.

Are the treatment activists paying attention to this dialogue on treatment in the context of vaccine trials?

Not really. I think they’re so involved with the enormity of trying to access treatment for hundreds of thousands of infected people that they haven’t really focused on breakthrough infections. However, I think they would see this debate as an opportunity to push the envelope. It comes back to the question of whose responsibility it is [to provide treatment].

What is your answer to that question?

I think it should be the researchers’ responsibility, until we find a mechanism to roll out a national program. We should be responsible for setting up the model.

Do you have a vision for that model?

We would have to work either with life insurance companies or private medical aid organizations to develop a trust fund. When people need treatment, wherever they are in the country, there can be confirmation that they were on a vaccine trial. Then the fund would release money for them to get access to treatment and monitoring.

You haven’t done microbicide trials at your site, but is your sense that their approval process has been different than for vaccines?

They seem to be a lot less controversial. The interesting thing is that no one has ever bothered asking [people running those trials] about what they’re going to do in the event of a breakthrough infection. I maintain that it’s because microbicide trials happen in women. In fact, when I once challenged [an important decision-maker] on this issue, he said to me, “Well, you know, with vaccines you [the researcher] put something in someone’s arm. With microbicides, a woman does it to herself.” So if we scientists give someone an injection, that makes us more responsible? I think this reflects different ethics for different cohorts and different interventions.

Have there been trials of other [non-HIV] vaccines in Soweto?

There was a Phase III pneumococcal vaccine trial [completed in 2001] that was pretty amazing. It involved almost 40,000 children, and less than 10% were lost to follow-up. Another nice thing was that, at the time the study was done, there was no HiB [Hemophilus influenza-B] vaccine available—so they compared pneumococcal plus HiB vaccination to HiB by itself. That brought an overall therapeutic benefit to the program. The experience also showed that that the community is willing to be involved in vaccine trials and even to allow infants to take part.

What would it take in South Africa to get an HIV vaccine trial going in children?

I think these trials are plausible and feasible if we present them as a strategy to prevent mother-to-child transmission.

Do you think that pediatric trials will have to wait until efficacy trials have been done in adults?

I would hate for that to happen. Once we have data on safety and dosing in adults, we should be able to move into safety and dosing in children, adolescents and infants. It would be terrible to wait until we’re halfway through an adult efficacy trial before we start studies in children and adolescents.

In your research on what’s behind the high infection rate in young South African girls, you’ve found that some girls in Soweto are sexually active as early as age 10 [See Article]. How are you reaching out to such young people?

We’ve employed an HIV-infected teenager, a 19-year-old girl, in our vaccine unit. She started having sex when she was nine years old and fell pregnant when she was 15. By then she was HIV-infected. She now goes around schools and talks about HIV/AIDS, about vaccines, about risk-reduction counseling.

Next year, we want to do surveys amongst teachers, parents and adolescents, asking the adolescents if they would they be part of a vaccine study and asking the adults if would they allow or encourage their children or students to take part, and what they think the issues are. This could give us enough data to challenge the current preference for trials only with adults in South Africa.

I’ve had some informal discussions with parents of 9- and 10-year-olds, asking if they would put their kids in an HIV vaccine trial. The answer is usually affirmative. I haven’t met one parent who was completely appalled by the idea.

Where is the country now on the issue of clade and the importance of matching or not matching vaccines?

If there’s one thing we’ve achieved this year in South Africa, it’s that scientists in the country have agreed on the importance of going ahead with both matched and unmatched vaccines. [South Africa’s heterosexual epidemic is almost exclusively clade C].

Has the clade issue contributed to delays in approving the proposed trials? [Two of the three pending protocols involve non-C vaccines.]

No, I don’t think so, not at all. When we submitted the non-clade C proposals, we were very clear why we need to do them. Merck has shown that there are cross-clade immune responses to their vaccine. These findings helped push the scientific envelope in the country.

We were clear that the MVA-based vaccine [based on clade A] was from a clade common in East Africa, and that this trial is a good opportunity for further collaboration with other African scientists. Also, the Merck trial provides a chance to participate in a multinational trial, which is quite exciting.

Initially there was a push in South Africa and elsewhere for clade-matched vaccine trials. I think there was a good political and scientific rationale to push clade C vaccines, because at that stage, nobody was working on anything except clade B. By pushing C, we got a whole lot of people interested in non-B clades. But now that we’ve done that, let’s look at the science, and at the value of testing unmatched vaccines.

If you ask us what we have achieved this year, it’s that there are three vaccine trials waiting for approval—which is phenomenal.