World Aids Day 2013: Halfway to Zero

Each year World Aids Day helps raise awareness around the world. It’s also a time for everyone involved in the fight against HIV to step back and assess our progress. Looking at the HIV community as a whole and Cavidi in particular, I can say it’s been a good year overall. We have seen great progress in the treatment of HIV worldwide. At the same time, these developments have further clarified the challenges that remain to providing universal access to proper HIV treatment and prevention. 

World Aids Day Graphic from http://worldaidsdaynw.org/

World Aids Day 2013 marks the halfway point of UNAIDS’ Getting to Zero initiative. This ambitious initiative has three core objectives to achieve by 2015:

• Zero new HIV infections
• Zero AIDS-related deaths
• Zero HIV-related discrimination

So where does the world stand at the halfway mark? Many of the statistics coming from the WHO are cause for optimism taken at face value. But with an estimated 2 million people contracting HIV each year and over 1.5 million deaths attributed to AIDS, it’s clear that we are still a long way from zero. 

Given the complexity of these issues and the limitations of the available data, it’s often quite difficult to get a fix on where we are on our journey to zero. Roger Tatoud explains just how difficult this task can be in an excellent post he wrote a few weeks ago on the 0 Incidence blog. In his post, Roger boils down a sea of data into three clear graphs that together start to give us insight into where we stand today. I was particularly interested in his analysis of how we are doing in terms of providing access to HIV treatment. The year-on-year increase in the number of people able to access HIV treatment has been rising steadily since 2006. That’s all good. However, the rate of change year-on-year over the same period has been in steady decline, meaning that although more people are accessing HIV treatment each year, the rate at which people are accessing HIV treatment is slowing down. That’s not good. Roger concludes, “This suggests that current approaches to deliver treatment are reaching a limit (or that something is limiting further expansion) and that for treatment to reach more people more effort will be needed or that we will need to do things differently.” 

Part of that difference may well be an increased role for viral load monitoring in the treatment of HIV. 2013 saw viral load monitoring receiving increased attention among the world’s most influential healthcare bodies such as WHO, UNAIDS, UNITAID and MSF. A decade after acknowledging the importance of HIV viral load monitoring, the World Health Organization 2013 revised guidelines, calling for developing countries to roll out routine virological monitoring, with viral load tests at both six and twelve months after treatment initiation, and then at least every twelve months thereafter. In this way, treatment adherence problems are corrected more quickly and patient treatment can be adjusted if the viral infection is not responding to therapy. 

This decision was further supported by a report from Médecins Sans Frontières (MSF) that highlights the importance of routine HIV viral load monitoring in low-income countries. Today, most clinics in resource-limited settings try to monitor disease progression with CD4 tests alone. The MSF research provides ten specific benefits that programs in developing nations can hope to achieve by adopting the WHO recommendation for routine HIV viral load testing. Among them are confirmation of treatment failure, prevention of HIV mother-to-child transmission, and improvement in HIV treatment outcomes in low-income countries. If realized, the benefits outlined in the MSF report would certainly move us closer to UNAIDS Getting to Zero goals. 

The increased interest in viral load monitoring witnessed over the past year has been accompanied by increased interest in point-of-care solutions. The idea is to get the HIV monitoring test out to where the problem is. I sense this is a reaction to address the inadequacies of centralized testing, particularly in resource-limited settings where simply transporting samples to a central lab can be a limiting factor. While the point-of-care initiatives are a welcome development to dysfunctional centralized options, there is middle ground that needs to be kept in mind.

Any solutions for HIV treatment have to work with the realities of existing laboratory infrastructure. The WHO has designated five tiers of laboratory infrastructure.  Each has its capabilities in terms of what types of tests can be run and the throughput that is possible. This, in turn, influences the access to testing that we can expect from any tier. For instance Tiers 0 and 1 may interact with a large population of people living with HIV, but since there is no lab infrastructure and a shortage of skilled staff exists at that level, testing is limited to one-at-a-time, point of care testing with low throughput.  We have drawn on throughput projections and population geography to provide a picture of  potential access to monitoring at the different levels. 

If we estimate the global population of people living with HIV to be at around 34 million, we can divide them by this type of access. There we see that the centralized testing schemes used by reference labs in Tier 4 could access about 6 million people living with HIV and this is where, traditionally, much of the emphasis has been placed. Primary care facilities and community outreach programs in Tier 0 and 1 could reach about 8 million people living with HIV and this is where point-of-care solutions can have the greatest impact. But with near-patient testing, regional and district-level facilities in Tier 2 and 3 could provide access to over 20 million or 60 % of cases. Today, Cavidi’s ExaVir™ Load test is the only test capable of providing viral load monitoring coverage on a regional and district level.

These middle tiers are where Cavidi focuses its efforts both with our current product, ExaVir™ Load, and with our R&D efforts to develop new monitoring solutions that will increase throughput and access even further. I’m pleased to announce that we have made significant progress in both areas over the past year. 

In 2013 we reached another milestone with our ExaVir™ Load HIV viral load monitoring kit as we began shipping to the Philippines. This marks the 25^th country to adopt ExaVir™ Load for clinical use in addition to over a dozen other countries where the test is currently being evaluated for use. The test offers the same sensitivity and accuracy of Tier 4 reference tests but, unlike those tests, it can be run in Tier 2 and 3 facilities – and at a fraction of the cost. 

Cavidi’s new Automated Monitoring System will provide viral load and be adding other optional HIV test kits, such as CD4, EID, and drug resistance in one robust bench-top unit.

We are also making steady progress on the next generation of HIV viral load monitoring diagnostics. Codenamed the Automated Monitoring System, the new system is now in the prototype stage. This new product uses the same proven RT-technology found in our ExaVir™ Load test but it is fully automated, requiring less time from lab technicians and greater throughput. In addition to viral load testing, we will be adding other optional HIV test kits like CD4, EID, and drug resistance in one bench-top unit.  Like ExaVir™ Load, our new system is ideally suited to the near-patient testing needs of Tier 2 and 3 regional and district level facilities. Bringing this product to market will be a game changer for increasing both access and quality of HIV treatment globally. I look forward to sharing more news on the project throughout 2014. 

While 2013 saw progress in the battle against HIV, it’s clear that we still have lots of work ahead of us. That’s why we need to ensure that the public remains aware and vigilant. My colleagues and I at Cavidi will continue to work to increase awareness, access, and quality of HIV treatment worldwide. In the interest of raising awareness among your peer network, I hope you will share this post. If you would like more information about Cavidi’s work in this area, feel free to contact me directly. 

HIV Viral load monitoring: from patient to public health issue

Amazing strides have been made in providing access to Antiretroviral Therapy (ART) in resource-limited settings. In 2011, around 8 million HIV-infected patients living in low- and middle-income countries have access to ART compared to just 400,000 a decade a go. Greater access to Antiretroviral drugs (ARVs) is good news, but it has magnified the need for HIV viral load monitoring to properly administer these drugs. A recent Médecins Sans Frontières (MSF) review of data from 12 low- and middle-income countries found that only 2% of patients had ever received a HIV viral load test result, no less received them every 6-months as recommended by the World Health Organization (WHO).

One Hope by Joe Average was used for the XI International AIDS Conference in Vancouver in 1996The direct benefits of HIV viral load testing to the patient are well documented in terms of better outcomes with decreased mortality. That’s why HIV viral load testing has long been a standard part of treatment in middle- to upper-income nations. But if we look beyond the patient, there is an equally compelling public health case to be made for ensuring access to HIV viral load testing in the low- and middle-income countries where the vast majority of HIV patients live. Here are four ways HIV viral load testing protects the public as well as the patient. 

 1. Help clinical resources go further by targeting counseling where it is needed. Some patients will take their medication as instructed – many will not. Noncompliant patients will usually show elevated viral activity which can lead to increases in treatment failure, transmission, comorbidity, drug resistance, and mortality. Counseling has been found to be very effective at helping with adherence issues but is labor intensive.  This can be an enormous strain affecting the entire clinic. With HIV viral load monitoring the clinic can identify noncompliant patients early and more efficiently target counseling only to those who need it. 

 2. Reduce treatment costs by helping less-expensive first-line ART last longer.  HIV mutates at such a remarkable rate that it is a foregone conclusion the virus will eventually be able to resist first-line treatment. The only question is when. If proper concentrations of the drugs are not properly maintained in the blood it makes this job a lot easier for the virus and thus will lead to treatment failure sooner. Monitoring viral load helps identify viral activity and address it before the treatment fails and the patient needs to be moved to a new treatment (if available).  Without viral load measurement, doctors can also misattribute patient symptoms to treatment failure and switch them before it is required. Since first-line ART is always cheaper than second-line treatment (in some cases one-quarter the price), keeping patients on first-line treatment for as long as possible helps resources go further. 

3. Reduce the spread of HIV.  Studies have found that transmission among HIV-infected persons with a viral load below 1,500 copies/ml is rare.  Put simply, if there is no virus circulating in the patient’s blood, then they are unlikely to spread the disease.  So managing HIV viral load can, in itself, contribute to prevention. But you can’t manage what you can’t measure. This is where HIV viral load monitoring contributes. A mathematical model published in the AIDS journal this year demonstrated that routine virological monitoring combined with ART can lead to a 31% reduction in HIV transmission. 

 4. Combat the global problem of HIV drug-resistance. If HIV is allowed to remain active in the presence of drugs meant to suppress it, then it is just a matter of time before it will produce a viable mutation that will be resistant to the drug. We are already seeing this. A 2010 study in resource-limited settings found that in the absence of HIV viral load monitoring, the incidence of drug-resistant mutations following treatment failure is high.  Of course this causes secondary resistance in these patients. But there’s a knock-on effect in that these resistant patients begin spreading a strain of HIV to others that drugs can’t treat. MSF reports that primary resistance in sub-Saharan Africa is already at 5.6% overall. If we look at countries where ART have been dispensed without HIV viral load monitoring for 10 years or longer we see a rate of 12%.  Worse still, the drug-resistant mutations that are being found in newly infected people who have never been on treatment are resistant to both first- and second-line drugs. That’s a trend that could unravel much of the progress made over the last 20 years in the battle against HIV. 

When we look at HIV viral load monitoring from a public health perspective it becomes clear that the issues above are not limited to low- and middle-income countries. First, because any HIV viral load monitoring solution that is inexpensive enough to be viable in resource-limited settings could lower the cost of HIV treatment for any healthcare system. Secondly, because issues like the spread of HIV infection and drug resistance know no borders. HIV/AIDS is a global problem and affordable HIV viral load monitoring is an important part of the solution whether you are in Nairobi, New York, Melbourne, Lusaka, London, Harare or Hong Kong. 

 As access to ARVs grows across low- and middle-income regions, so does the public health imperative to dispense those drugs in a responsible manner with regular HIV viral load monitoring of patients.  As MSF put it, “Funding the implementation of viral load should not be seen as a luxurious and avoidable expense, but should rather be recognized as a necessary and potentially cost-saving addition to current international commitments to scaling up treatment.”  Today, Cavidi and others have the technology to address this public health issue and provide inexpensive, near-patient HIV viral load monitoring where ever it is needed. Doing so will not only serve the patient but protect the public. All we need is the collective will to make it happen. One more reason why the time for HIV viral load testing is now. 

John Reisky de Dubnic

CEO

Cavidi

Further reading:

• Aghokeng AF, Kouanfack C, Laurent C, Ebong E, Atem-Tambe A, Butel C, Montavon C, Mpoudi-Ngole E, Delaporte E, Peeters M: Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients. AIDS 2011, 25: 2183 –2188.
• Estill J, Aubriere C, Egger M, Johnson L, Wood R, Garone D, Gsponer T, Wandeler G, Boulle A, Davies M-A, Hallett T, Keiser O: Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa: A mathematical modelling analysis. AIDS 2012, 26: 1413.
• Hamers RL, Wallis CL, Kityo C, Siwale M, Mandaliya K, Conradie F, Botes ME, Wellington M, Osibogun A, Sigaloff KCE, Nankya I, Schuurman R, Wit FW, Stevens WS, van Vugt M, de Wit TFR: HIV-1 drug resistance in antiretroviralnaive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis 2011, 11: 750 –759.
• Lynen L, Van Griensven J, Elliott J: Monitoring for treatment failure in patients on first-line antiretroviral treatment in resource-constrained settings. Curr Opin HIV AIDS 2010, 5: 1–5.
• Médecins Sans Frontières: Undetectable – How Viral Load Monitoring Can Improve HIV Treatment in Developing Countries, July 2012
• Murtagh M: UNITAID HIV/AIDS Diagnostic Landscape 2nd Edition. 2012.
• Quinn T, Wawer M, Sewankambo N: Viral Load and Heterosexual Transmission of Human Immunodeficiency Virus Type 1. N Engl J Med 2000, 342: 921–929.