The failure of antiretroviral therapy and the appearance of drug-resistant HIV strains continue to hinder efforts to keep HIV-positive individuals healthy. Unfortunately, the tests needed for early detection of antiretroviral therapy failure and drug resistance are expensive and not widely available in many countries with a high HIV prevalence. But the provision of such tests may benefit from an unusual source: old shipping containers.

Immunological and viral load testing are necessary to slow the emergence and spread of drug-resistant HIV strains. A recent meta-analysis published in The Lancet Infectious Diseases revealed that patients whose viral loads were monitored frequently (at 3-month intervals) were less likely to harbor drug-resistant HIV viruses at the time of virological failure than patients who were monitored less frequently or not at all. (Virological failure occurs when drugs are no longer able to suppress HIV replication and viral loads increase. Patients with viral loads of 1000 viral RNA copies per milliliter of blood or higher are considered to have experienced virological failure.)

Numerous studies have shown that resistant HIV viruses can be transmitted, causing some newly infected individuals to harbor HIV viruses resistant to antiretrovirals even before beginning treatment. The possibility of transmission of resistant viruses makes the expansion of viral load testing even more important — monitoring the viral loads of patients on antiretroviral therapy (ART) not only protects the patient from the harmful effects of virological failure and the emergence of drug resistant strains but it also protects the patient’s sexual partners (and the partner’s partners, and so on) from drug-resistant HIV.

It is clear that viral load testing helps limit the emergence, and thus likely the spread, of drug-resistant HIV. The problem is now one of provision: How can we make sophisticated laboratory tests available to populations without access to modern laboratory facilities? One answer comes from the South African company Toga Labs, which turns old shipping containers into HIV testing labs. The use of these “container labs” has garnered some attention in the media over the past several years (recently, by Reuters and Health-e) and has been discussed in the academic press (see, for example, this Commentary piece in Nature Methods). The labs are equipped to provide the viral load testing necessary for early detection of virological failure. These labs can also do CD4 count testing, which is routinely used to determine when to start patients on ART. Therefore, these labs also could be used as part of a program to expand ART coverage.

Unfortunately, there seems to be little (publicly-available) analysis as to the cost-effectiveness of these container labs as compared to traditional labs in stationary buildings. However, even without a clear cost benefit, container labs are advantageous for two reasons. First, the labs are “built” using existing materials (i.e., the old shipping containers) and thus do not require the consumption of other resources. Second, the labs are somewhat portable, as they can be carried anywhere that a large truck can go. The ability to transport the lab to different areas would extend access to medical testing facilities more than constructing a stationary lab. Even if the container lab could not be transported into the villages that it is meant to serve, it could likely be brought close enough so that HIV patients would not have to travel far to get to the testing facility — walking two miles to a lab parked near a major highway is much more feasible than walking forty miles to the closest city with permanent lab facilities.

Of course, portable labs are not the only solution to the lack of adequate viral load testing services. The development of simple, inexpensive point-of-care tests could also dramatically expand access to viral load testing. Building or upgrading labs in stationary buildings is also a possibility. The point I am making here is not that container labs are the best way to expand access to viral load testing but rather that they could be part of the solution to this problem. Cost and feasibility will always be major barriers in the implementation of public health interventions. Because of this, as global health practitioners, we need to make sure that we identify and evaluate innovative solutions to these problems — like turning old shipping containers into medical testing labs.

More information:

American Journal of Epidemiology: Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients

The New England Journal of Medicine: Viral load and heterosexual transmission of human immunodeficiency virus type 1

BMC Infectious Diseases: Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: A cohort study

JAIDS: A population-based approach to determine the prevalence of transmitted drug-resistant HIV among recent versus established HIV infections: Results from the Canadian HIV strain and drug resistance surveillance program

The New England Journal of Medicine: Antiretroviral-drug resistance among patients recently infected with HIV

[Editor’s note: This is the first in a series of posts covering topics related to drug resistance, including causes, effects, what is being done to fight drug resistance, and what needs to be done to limit the harm caused by drug-resistant pathogens.]

The discovery of penicillin in 1928 was one of the greatest medical discoveries to date, and since their introduction, penicillin and other antibiotics have saved an incredible number of lives. Unfortunately, it didn’t take long for the bacteria to fight back.

The discovery of penicillin-resistant bacteria within a year of the first clinical use of the antibiotic would serve as a sign of things to come. Today, there are few (if any) widely used antimicrobial drugs that have not been rendered less effective by the emergence of resistant pathogen strains. The fast replication cycles of bacteria and viruses and the mistakes made by their replication machinery give these pathogens the ability to respond to and overcome drug pressures. With penicillin, for example, replication errors allowed some formerly penicillin-sensitive bacteria strains to evolve so that the targeted bacterial proteins no longer interact with the antibiotic. Other bacterial strains acquired new genes that allow them to produce proteins that degrade penicillin, rendering it ineffective and allowing these bacteria to survive.

Drug resistance continues to be a major obstacle in reducing the prevalence of the “big three” infectious diseases: HIV/AIDS, tuberculosis (TB), and malaria. The recent emergence of malaria strains resistant to artemisinin, one of the most effective anti-malarial drugs and sometimes the only drug that can effectively kill the deadly Plasmodium falciparum parasite, serves to highlight how troublesome — and downright frightening — drug resistance can be.

Of course, drug resistance is not just a problem for the “big three.” Drug-resistant strains of H1N1 (swine) flu have been found in Canada, Denmark, Japan, and Hong Kong, which does not bode well for the upcoming flu season. Drug-resistant staph infections are also a significant problem. It has been estimated that methicillin-resistant Staphylococcus aureus (MRSA) was responsible for 94,360 infections and 18,650 deaths in the US in 2005.

Drug resistance is not just a public health issue — it is also a human rights issue. Article 25 of the Universal Declaration of Human Rights acknowledges the right to medical care, and as one of humanity’s greatest achievements in medicine, antimicrobial drugs are a necessary part of adequate medical care. Unfortunately, the actions of doctors, pharmacists, consumers, and others — and the lack of appropriate action by governing bodies — continue to promote the emergence and spread of drug-resistant pathogens. Of course, the emergence of drug-resistant pathogens is not in itself a human rights violation, but the (mis)handling of drug-resistance issues by medical and public health practitioners clearly has human rights implications. Human rights implications arise from the fact that much can be done to reduce the emergence of resistant pathogens and to ensure that people will have access to life-saving antimicrobial drugs when they are needed.

Here, MRSA serves as a good example. It has been shown that active surveillance measures in hospitals can reduce hospital-acquired MRSA infections. However, many hospitals in the US have failed to implement such programs. Typically, surveillance programs are not adopted because of high cost or limited resources, even in wealthier countries.

But what about the people who get MRSA infections during their hospital stay? If surveillance programs are evaluated from a human rights perspective, these programs can be viewed as protecting people’s right to health by protecting them from potentially deadly MRSA infections. Put another way, hospitals that decide not to implement surveillance programs are depriving patients of that protection of their right to health. A person’s right to health should not be denied without an extremely compelling reason (for example, because doing so would greatly infringe upon the rights of others) and should certainly not be done simply because of (bearable) cost, inconvenience, or plain unwillingness to adopt life-saving measures.

Human rights issues also come into play when determining how to respond to outbreaks of disease caused by drug-resistant pathogens. In these situations, the rights of a few (the infected individuals) are often in conflict with the rights of many (the general public). Striking the proper balance between protecting the rights of both groups has been a difficult thing to do.

Attaining that proper balance has been widely discussed with respect to multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, including in a recent Health and Human Rights article. On one hand, the public needs to be protected from the disease, prompting calls for compulsory treatment and quarantine of individuals infected with MDR- or XDR-TB. On the other hand, such measures — particularly forced quarantine — infringe upon the rights of the infected individuals. The example of MDR- and XDR-TB demonstrates the need for medical and public health practitioners and policy makers to consider human rights implications when determining the best response to outbreaks of drug-resistant disease.

Because drug resistance further complicates already complicated issues surrounding infectious disease control, it is imperative that human rights and public health practitioners understand drug resistance so that infections with drug-resistant pathogens can be prevented and treated in ways that best protect the rights of everyone involved.

More Information:

WHO: Drug resistance

CDC: Antibiotic/antimicrobial resistance

The New England Journal of Medicine: Artemisinin Resistance in Plasmodium falciparum Malaria

Infection Control and Hospital Epidemiology: Society for Healthcare Epidemiology of America guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and Enterococcus

The World Health Organization estimated 9.27 million cases of TB in 2007, a significant increase from 6.6 million cases in 1990. The majority of these cases are found in the South-East Asia region, which accounts for 34% of all new cases, and sub-Saharan Africa, which has the highest TB mortality rate in the world. People with health conditions that weaken the immune system like HIV infection, substance abuse, or malnutrition are more susceptible to the disease. A recent study showed that one-fourth of all TB-related deaths were in patients who were also HIV-positive.

No new classes of TB drugs have been created since the 1960s, and few clinical trials have been conducted using modern regulatory standards. To address this need, research groups are focusing on novel approaches to TB therapeutics. The Global Alliance for TB Drug Development (TB Alliance) recently announced four research partnerships that will explore new methods of treating drug-resistant TB. One of these collaborations, led by Anacor Pharmaceuticals, will provide any new compounds developed to the TB Alliance royalty-free.

Another recent study has found that in an eight week exploratory trial with MDR-TB patients in South Africa, the experimental drug TMC207, in combination with the standard MDR-TB drug cocktail, cleared TB bacterial traces in the sputum of 48% of patients, as compared to 9% of patients given only the standard cocktail. The experimental drug appeared to work faster than standard MDR-TB drugs in clearing TB, possibly because of its unique mechanism of action. Current treatment courses last for at least 18 months because MDR-TB drugs take more time to effectively clear the disease. For example, 81% of MDR-TB patients in Peru treated with DOTS-Plus therapy were cured after four months, versus only 40% after two months. Further proof-of-efficacy studies are being conducted with TMC207 now, and will demonstrate if it is effective as a long-term treatment for various types of TB. If approved, this drug could be a significant advance over current treatments, which can be lengthy and toxic.

Related TB links:

Airborne: A Journey into the Challenges and Solutions to Stopping MDR-TB and XDR-TB

Improving tuberculosis care in low income countries – a qualitative study of patients’ understanding of “patient support” in Nepal

Global tuberculosis control – epidemiology, strategy, financing

Global Health Delivery Online – Drug-Resistant TB

TB Alliance Annual 2008 Report

Stop TB Partnership

South Africa leads hunt for killer TB vaccine

South Africa: TB Vaccine trials for babies