New report finds missing and incomplete data imperils the global HIV/AIDS response

amfAR and AVAC call for improved, transparent and timely data collection

A new report from amfAR, The Foundation for AIDS Research, and AVAC outlines the need for a new approach to tracking data to guide the key decisions that shape the response to the HIV/AIDS epidemic. Critical and expensive decisions made with incomplete data are undermining the response—even as the systems for collecting this data continue to improve, the report found. Data Watch: Closing a Persistent Gap in the AIDS Response outlines corrective steps to sustain and expand the progress made in the past few years in the AIDS response and lays out key areas where better, more complete data is needed, including:

  • What proportion of people with HIV globally who are taking antiretroviral drugs remain connected to a clinical provider and have their virus fully suppressed, enabling them to remain healthy and avoid transmitting HIV to others?
  • What proportions of those communities most impacted by HIV (e.g., young women in Africa, gay men and other men who have sex with men, transgender individuals, sex workers, people who inject drugs) do not have access to effective HIV prevention tools due to pervasive stigma or discrimination?
  • Is global AIDS funding focused on those programs that will have the greatest impact in reducing transmission and disease burden worldwide?

The report, supported in part by the M•A•C AIDS Fund, makes the case that if we are to achieve ambitious new targets aimed at ending the epidemic by 2030, we must improve our data systems for the HIV response now. Data Watch updates amfAR’s and AVAC’s 2012 Action Agenda to End AIDS, which made the case for a more businesslike approach to ending the epidemic and proposed a multi-year plan with concrete strategies, targets and timelines.

“There is no doubt that the data we have shows that we are making progress in the fight against HIV/AIDS. Importantly, we are moving toward a ‘tipping point,’ when for the first time the number of people with access to HIV treatment will exceed the number of people who become infected,” said Mitchell Warren, AVAC executive director. “But to keep up the momentum, we must improve data systems and identify specific milestones that we need to meet over the next one to three years to ensure we get on – and stay on – target to achieve these ambitious goals.”

The report documents many cases where data is incomplete or missing, finding that sometimes necessary data collection systems are not in place. For example, in most low- and middle- income countries there is very little tracking of viral load—a measure of the amount of HIV in a person’s bloodstream—among people being treated for HIV. In many cases, data exists but is incomplete or not being optimally analyzed. Poor or missing data limits our ability to drive strategic action and accelerate progress toward ending AIDS.

“Good information is critical for making good decisions, and when resources are limited, data matters even more,” said Greg Millett, amfAR’s vice president and director of public policy. “With global AIDS funding falling far short of what is needed, we must maximize the impact of every dollar. The bottom line is clear: more complete and timely data will help save more lives.”

The report calls on UNAIDS, the US-funded PEPFAR program, and the Global Fund to Fight AIDS, Tuberculosis and Malaria to dramatically improve their collection, analysis and reporting of HIV/AIDS information. It outlines which data matters the most, including:

  • Coverage of core interventions including HIV testing, antiretroviral therapy, voluntary medical male circumcision, prevention of vertical transmission, male and female condom availability, and harm reduction programs.
  • Disaggregated information by gender, age, key population status, and other key factors. Overall numbers are insufficient.
  • Indicators of service quality including percentage of people on ART with undetectable viral load tests, retention in care data and more.
  • Impact data on incidence, HIV prevalence and AIDS-related deaths are the ultimate indicators of success.
  • Results-linked expenditure data sheds light on where programs are achieving results and on how reallocation of resources could improve program impact.

As part of the Action Agenda to End AIDS, amfAR and AVAC launched Data Watch to help advocates track progress—and to hold the key sources of global HIV information accountable for timely, accurate reports. An Action Agenda to End AIDS, launched by amfAR and AVAC at the 2012 International AIDS Conference, outlined key actions that need to be taken in 2012–2016 to lay the foundation to end the AIDS pandemic. For more information, visit endingaids.org.

The Big Picture of Small Molecules for Curing HIV Infection

Welcome to the first installment of a periodic series of P-values posts by guest authors. We’ll be featuring scientists, advocates and implementers from around the world. If you’ve got a point of view you’d like to share or a topic you’re expert in and would like to explain, Let us know.

This post is the first of what will be a series of posts from scientists working on cure research. Dr. David Margolis and Karine Dubé of The Martin Delaney Collaboratory of AIDS Researchers for Eradication explain one strategy being pursued by scientists as a possible way to cure HIV. After reading this, if you want to learn more check out this video on related research.

Highly active antiretroviral therapy (HAART) is a true miracle of modern science and has contributed to saving millions of lives worldwide. HAART can successfully reduce plasma HIV-1 levels in adherent HIV-positive patients to below the detection limit of clinical assays. As wonderful as HAART is, it does not clear HIV from the human body, but can only suppress it. HIV remains dormant or latent in around 1 out of every million white blood cells in suppressed patients in the form of HIV provirus that becomes integrated within the human genome (also called the reservoir).

There are several approaches to eradicating latent HIV infection that have been proposed by the Martin Delaney Collaboratories, including, but not limited to: intensification of HIV treatment in the acute phase of infection, gene therapy and stem cell transplantation research as well as latency reserving agents. Latency reversing agents are small pharmacological molecules that would help uncover where HIV is hiding in the cells of HIV-infected patients whose viral load has been suppressed.

The Collaboratory of AIDS Researchers for Eradication – CARE – endorses the approach of small pharmacological molecules to finding a cure for HIV infection. We believe that this method represents the safest, most scalable, and accessible strategy to eradicating HIV in the future. By using established drug discovery tools, we hope to launch a pipeline of small pharmacological molecules to be used in human studies. These small molecules would induce the expression of the replication-competent latent HIV proviral genomes within resting CD4+ T cells and make them susceptible to the immune clearance and the effect of HAART. In the literature, this is also called the “shock and kill” strategy or “induction and clearance.” This method relies on reactivating the rare remaining reservoirs while patients take their HAART.

Our priority is to discover new molecules that are safe and can act alone or in synergy with other drugs to reactivate HIV virus transcription. We screened over 10,000 new pharmacological molecules and we are examining their mechanisms of action. As these new compounds have various levels of potency and toxicity, it is important to evaluate them carefully using cell models and animal models before advancing them into clinical testing. Experiments are being conducted in vitro (in artificial laboratory cell models), ex vivo (in patient’s cells studied in the laboratory) and in vivo (in animal models or real human patients) using various cell lines and animal models, included humanized mice and non-human primates.

The small pharmacological molecules being proposed would act as inducing agents to disrupt the state of proviral latency. Examples of small molecules that have been studied include inhibitors of histone deacetylase (HDAC) that play a role in maintaining HIV in a transcriptionally silent state. For example, Dr. Archin and colleagues demonstrated in a proof-of-concept study that a single dose of the drug vorinostat, an HDAC inhibitor, can disrupt HIV latency in HIV-positive patients on HAART. HDAC inhibitors have several advantages compared to other latency reversing agents. Because they have also been studied extensively as part of anticancer trials, we know more about their toxicological and pharmacological effects at this time.

Studying small pharmacological molecules also means that we need to carefully examine the regulatory pathways for these drugs. For example, the positive transcription elongation factor b (P-TEFb) plays an important role in regulating HIV transcription. When P-TEFb is active, this means that HIV viral transcription is stimulated. Another protein required for HIV expression is NF-κB, which is an activating regulatory protein needed for the transcription of many genes.

We are also studying molecules that induce signaling using the protein kinase C (PKC) pathway. Some of the PCK agonists under investigation include prostatin (which can induce transcription of latent HIV-1 in J-Lat cells and peripheral blood mononuclear cells (PBMCs) from HIV-positive patients on HAART). Two other PKC agonists under study include bryostatin and ingenol; however less is more about these compounds’ ability to safely induce HIV expression in vivo.

At this time, we cannot predict which compounds or combination of compounds may be effective at inducing expression of proviral DNA. We hope to investigate synergy both mechanistically and mathematically. Ideally, the chosen pharmacological molecules will reactivate latent HIV provirus without inducing a global activation of T cells. We also hope to get around the problem of toxicity by using low concentrations of the most effective inducing agents.

Once the HIV provirus is being expressed, the immune system needs to kill the infected cells. It will thus be important to re-invigorate the immune system of HIV-infected patients to ensure an effective immune response, so latency reversing agents can be used with immune-based therapies. For example, some of the immune cells could be expanded ex vivo and then be re-infused into HIV-infected patients.

Scientists within the Collaboratory are also working on ways to improve measures of the HIV reservoir. As of now, the quantitative viral outgrowth assay is the gold standard in terms of measuring replication-competent proviruses from resting CD4+ T cells. We are also using digital droplet PCR testing to quantify HIV DNA.

We are excited about the prospect of studying new latency reversing agents – as well as combinations of agents – that would be capable of aborting the state of HIV proviral quiescence. This strategy offers a diversity of options for the advancement of new compounds into clinical trials. It is also the safest way forward. We believe that small molecules represent the big picture for curing HIV infection.

CARE Website:
www.delaneycare.org

If you have any questions, please send them to:

  • Dr. David Margolis (david_margolis@med.unc.edu), Principal Investigator, The Collaboratory of AIDS Researchers for Eradication (CARE)
  • Karine Dubé (karine_dube@med.unc.edu) Program Manager, The Collaboratory of AIDS Researchers for Eradication (CARE)

No Turning Back in Fighting AIDS

This first appeared on PSI’s blog, Impact. 

The 20th International AIDS Conference marks a pivotal moment in the fight to end the AIDS pandemic – one that captures both the promise and the challenge of the years to come.

The past decade of financial and political commitment has resulted in a major expansion of access to HIV prevention and treatment services around the world. The public health impact of this commitment is both significant and unprecedented. Nevertheless, the gains are fragile and more must be done to reach everyone in need.

Almost three years ago, the United States government revitalized its commitment to ending AIDS through the ambitious goal of reaching an AIDS-free generation. Bipartisan support for the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and the U.S. contribution to the Global Fund to Fight AIDS, Tuberculosis and Malaria, continues to bring us closer to meeting this goal. Last year, President Obama announced that his target for supporting 6 million people on treatment by the end of 2013 was ahead of schedule. And Secretary of State John Kerry announced that 1 million babies globally have been born HIV-free thanks to PEPFAR support.

PEPFAR has been instrumental also in one of the most impressive turnarounds in the global response to AIDS, providing access to voluntary medical male circumcision (VMMC). VMMC has been shown to reduce a man’s chances of acquiring HIV from a female partner by nearly two thirds. PEPFAR had supported 4.7 million circumcisions by the end of 2013.

This support has been critical. Investments in the global AIDS response are working. In 2012, there were 2.3 million new HIV infections, the lowest number of annual new infections in almost a decade. Twenty-six countries have seen a 50 percent or greater drop in new HIV infections since 2001.

Globally, new partnerships are emerging – 53 percent of all HIV-related spending in 2012 came from the governments of countries tackling the epidemic domestically. Costs of treatment have also decreased dramatically. In the mid-1990s first-line antiretroviral therapy was $10,000 per person per year. In some low- and middle-income countries today it is $140. Through this efficient use of resources and an increased investment, we stand poised to reach an important ‘tipping point’ in the fight against HIV and AIDS, in which the number of individuals receiving HIV treatment exceeds the number of new HIV infections.

Sadly, the challenges ahead of us remain daunting.

To date, 16 million people in Africa who are eligible for antiretroviral therapy cannot access treatment. The treatment-eligible children living with HIV in sub-Saharan Africa are only about half as likely to receive antiretroviral therapy as HIV-positive adults. And though HIV rates are declining globally, rates for certain key populations appear to be rising in several regions.

Yet international support for HIV efforts has remained flat or – as in the case of PEPFAR – dropped in recent years. Without expanded and sustained investment in cost-effective treatment and evidence-based prevention, there is a very real danger that we will reverse the prevention gains of the last decade.

As Secretary Clinton said when she launched the US Blueprint for an AIDS Free Generation: “The goal of an AIDS-free generation may be ambitious, but it is possible with the knowledge and interventions we have right now.”

It would be a great tragedy to miss that opportunity. Rather than fall behind, we must step up the pace and end this once and for all.

We’ve come too far to turn back now.

What Does PrEP Mean for Condom Use?

PxROAR member Nicholas Feustel spoke about PrEP to the German magazine Männer. What follows is a translation into English Nicholas did for us. The original article, in German, is available here.

PrEP (pre-exposure prophylaxis) is all the rage in the HIV prevention field, especially since the WHO reviewed the strategy positively. It‘s a heated debate: Do we still need to wear condoms to prevent HIV infection? Are HIV-negative people going to ‘prep‘, i.e. taking the HIV drug Truvada, the only one of which we know for sure that it can prevent HIV transmission? To help answer some of these questions, we spoke with Hamburg resident Nicholas Feustel, who advocates for PrEP.

Nicholas, you work with “AVAC – Global Advocacy for HIV Prevention”. What do they do and why are you with them?

AVAC is an organization headquartered in the USA, which advocates for biomedical HIV prevention. Much of their work is introducing new prevention options in addition to condoms. I personally would like to advocate for the destigmatization of PrEP and people who would like to take PrEP here in Germany, even before PrEP becomes available here.

Is AVAC associated with the pharmaceutical industry?

No, not at all.

Who should be taking PrEP in your opinion? Many read the World Health Organization recommendations and thought, “just because I’m gay, it doesn‘t mean that I have to take medication”.

Yes, the WHO statement was misinterpreted by very many people. The WHO is not saying that all gay men are to take PrEP, but that all gays should consider it. The WHO recommendations act also as political statements rather than individual instructions. In this case, the WHO wants to push PrEP as an option, now that we know that it works.

However, who should be taking PrEP?

The main target group are people who do not or do not always use condoms during sex. It is for those who find that condoms are not an appropriate way to protect against HIV for them. With PrEP, they could still make the decision to protect themselves from HIV. There just are many who do not get along with condoms. Be it because they lose their erection when putting on the condom or they want to be close to their partner without a latex barrier. And we know that many of the new infections occur in supposedly monogamous relationships. Or, for example for women, if it is not possible for them to get their partners to use condoms, PrEP could provide suitable protective ability. Ultimately, I do not care why people don‘t use condoms, I do not want to judge their behaviour morally. Some just don‘t, period.

But haven‘t we got used to condoms more or less? Why change our strategy now?

No one is to change their strategy. If condoms work for you, absolutely continue to use them! But consider this: When HIV and AIDS emerged, condoms were the only way to have safer sex. As a result, we got drummed for 30 years that only gays who have sex with condoms are good gays. And sex without a condom is evil, evil, evil. Imagine we already had a PrEP drug when HIV and AIDS emerged. Would people have chosen to use condoms or take a pill once a day? I think people who do not or do not always use condoms are not “hedonistic bareback sluts”. Condoms are simply not the appropriate means to protect themselves from HIV. PrEP could be an alternative for them.

Condoms also protect against other sexually transmitted infections (STIs).

Yes, but not fully. Many STIs are transmitted during oral sex. If someone who doesn‘t use condoms, but takes PrEP to protect themselves from HIV, that‘s already quite something! And also, for a new PrEP prescription you have to go to see your doctor every three months, where they will test not just for HIV but other STIs as well. With PrEP, people engaging in high-risk behavior would go to see a doctor regularly and other STIs would be detected and treated early. This might even reduce the spread of other STIs.

The drug used for PrEP, Truvada, does have side effects, right?

Commonly seen side effects of Truvada are short term gastrointestinal problems which usually disappear after a few weeks, and not everyone will experience these. Long-term side effects may include impairment of renal function and bone density. Again, not everyone will experience these. The good thing is, if you take Truvada as PrEP you can stop taking it any time.If, however, someone has been infected with HIV, they will be on treatment for the rest of their lives. When arguing against PrEP because of side effects, one must always consider PrEP and HIV therapy are two different things. PrEP with Truvada consists of two active ingredients, normal antiretroviral therapies have three active ingredients, so there is the possibility of more side effects. And in HIV therapy there is also HIV in the body—this is also a health aspect.

But we still don’t know the long-term effects of PrEP and what risk there might be.

Of course we do not know what long-term effects PrEP may have. But Truvada has been used for 10 years in HIV therapy and is considered one of the best tolerated HIV drugs. And as the activist Peter Wiesner once said: Do we know the side effect of long-term, 20 years condom use? What does it do to our psyche? Instead of being able to have truly uninhibited sex – and I think there is nothing wrong with this desire – there is this constant fear of HIV, always the bad conscience, if you didn’t use a condom.

I think these considerations are, however, irrelevant, because we do know not everyone uses condoms all the time. We have not reached these people despite 30 years of prevention messaging around “fucking with condoms”. We could tell them for another 30 years, they just won‘t. Wouldn’t it be better to offer an alternative?

Why do we only hear of Truvada? Are there no other drugs available as PrEP?

Truvada is the only one we know from studies that, when taken daily, has a really high level of protection against HIV, higher than condoms. Currently there are also so-called long-lasting injectables in development. Then PrEP could perhaps mean just a once per month injection, or every three months, and you would be protected against HIV. However, it will probably take another 10 years until that is available.

For Truvada manufacturer, Gilead, PrEP must be a gold mine.

-ish! The patent for Truvada expires in 2017, then there could be generics, that is, exactly the same active ingredients, but from another manufacturer and cheaper. This means the prices will go down then. The PrEP market is not really exciting for Gilead, because it‘s not like millions of people will take PrEP. It will be only a small group of people who find that PrEP is the better method of protection for them. Do you think PrEP will play a role in Europe? I hope so! We have to admit: we are moving towards a post-condom era.

For those who want to use them, that’s perfectly fine, but there are also many men who simply can not be bothered to continue to use them after more then 20 or 30 years of condom use. Or young people who just haven‘t experienced all the dying. They say: Sure, we know the films of yesteryear, but now those taking drugs do well. And that is also what we want to achieve with the whole anti-stigma work: Nowadays you can live a normal life with HIV. Nevertheless, I find it is worth still trying to protect yourself from HIV. Science has moved on, and we know that those drugs that let people with HIV live long and healthy lives, and under successful therapy renders them virtually uninfectious, can also protect HIV-negative people from acquiring HIV.