The human immunodeficiency virus epidemic: A race against time for millions and the role of flow cytometry: A Caribbean and resource-constrained country perspective

DEMOGRAPHY

The Caribbean region is reported to have the highest HIV prevalence rates after Africa. The Caribbean comprises of 24 countries—French, English, Hispanic, and Dutch speaking—with a total population of about 36 million. The estimated income of this region in 1997 is US$ 40 billion, with a total regional health expenditure of US$ 2.6 billion (1).

The average HIV prevalence rate in the Caribbean is currently standing in the region of 2.3% with a reported range of 0.1 in Cuba to 5.6% in Haiti. The UNAIDS data published in 2005, for global figures ending in 2003, shows that there were an estimated 430,000 people living with HIV/AIDS in this region. Of this number, by far, the largest burden of 280,000 live in Haiti, 88,000 in the Dominican Republic, 29,000 in Trinidad and Tobago, 22,000 in Jamaica, and 3,000 in Barbados (2).

GLOBAL PROJECTION

Some projections, in relation to the development of the epidemic, suggest that the epicenter of the epidemic is now poised to move from its current location in East and South Africa to West Africa and South East Asia. This is based the on current models that imply there will be an additional 45 million people infected with HIV before the end of 2010. Furthermore, unless dramatic strategies of prevention, treatment, and immuno-modulatory interventions are globally implemented, this galloping epidemic is unlikely to reach its peak worldwide before the year 2050. Based on this scenario, there could be a staggering 30 to 140 million living with HIV/AIDS in India alone and another 32 to 100 million in China. A very large proportion of the 40 million people currently living with HIV will likely die in the next few years due to poor access to anti-retroviral treatment (ART) (3). A recent report from the UNAIDS/WHO, November 2005 update report on HIV, supports these projections, which confirms that despite some country success stories, there were 5 million new HIV infections and 3 million AIDS-related deaths worldwide in the year 2005 alone (2).

Although ART has well-defined benefits of longevity and quality of life when utilized optimally, the treatment still remains costly and logistically difficult to deliver and sustain. The anti-retroviral drugs in themselves are not curative and may have significant side effects, and therefore at best, they should only be considered as a stop-gap measure. This realization has driven the social prevention programs and a concerted search for both a preventative and a therapeutic vaccine.

IMPACT OF HIV IN THE CARIBBEAN

The economic losses predicted by the AIDS pandemic in this region is estimated at 5% of the GDP, equating to loses to the region in excess of US$ 2 billion annually (1). The consequences of this are tantamount to a crippling attack on the economic development of the region and the quality of life of its indigenes. The Caribbean, being a popular vacation location for both North America and Europe, will be a key player in the transformation, mobility, and dispersion of the virus. It has been established that the main subtype seen in the Caribbean is of the HIV-1, subtype B variety, which is the characteristic clade found in North America and Europe (2). It is therefore recognized that the interest of the global community is best served by making all efforts to assist vulnerable under-resourced regions like the Caribbean with their care and support programs (4).

COST OF RESPONSE IN THE CARIBBEAN

On the basis of the technical contributions of several consultancy agencies deployed in the region, it has been estimated that an early comprehensive response to the HIV epidemic in the Caribbean would require nothing less than US$ 3.4 billion annually (1). This figure however does not take into consideration the fact that even if these resources were made available, most of the countries in the region would not have the infrastructure to mount a response nor the capacity to utilize the funds. This invariably equates to an initial level of funding that is larger in scale than that estimated, and must factor into account the initial very high cost of capital investment for technology transfer and infrastructure upgrade.

REGIONAL RESPONSE AND POLITICAL WILL

Galvanized by what was transpiring in the galloping African HIV epidemic, a series of political events triggered the turning point in the formulation of the Caribbean regional HIV policy. The first debate on the global security implications of HIV took place in the United Nations in January 2000, and this was soon to be followed by the Caribbean conference on HIV/AIDS organized by the Health Economics Unit (HEU) of the University of the West Indies, held in Barbados on the September 11, 2000. The outcome of research done by this unit projected dire long-term human and socio economic consequences and exposed the general inadequacies of the prevailing health infrastructural and human capacity of the region to mount a response.

This was followed rapidly by the declaration of the Caribbean heads of governments, publicly recognizing that HIV was capable of reversing the developmental achievements that the region had gained in the previous three decades. The result of this was the establishment of the Pan-Caribbean Partnership against HIV/AIDS (PANCAP) in February of 2001. A similar declaration and framework was made in Abuja Nigeria in April 2001 by the African heads of state, who also clearly understood the risk to the growing regional insecurity of this expanding pandemic.

Finally in June 2001, a special session dedicated to HIV/AIDS was organized by the United Nations (UNGASS), which was successful in bringing HIV/AIDS to the political forefront and crystallizing the significance of this global demographic holocaust. There was a unified declaration of intent to establish a global alliance to address the HIV crises in all its ramifications, with intensified action and increased resources (4). A tangible outcome of this was the creation of the Global Fund through innovative public private sector partnerships to the tune of US$ 4.4 billion in pledges to effectively support over 128 countries through its Global AIDS Project (GAP) (3, 5). In July 2001, the Caribbean developed clear objectives for the region as outlined in the Caribbean Cooperation on Health Initiative document number two (CCH-II). This stance was reiterated at the United States/Caribbean high-level meeting on HIV/AIDS held in Guyana on April 20, 2002 (6). These declarations called for a fully integrated HIV/AIDS prevention, care, and treatment plan into mainstream national development programs by the year 2003, with the introduction of ART in a careful and monitored manner to improve adherence and effectiveness and reduce the risk of developing resistance.

But despite this, most countries in the Caribbean, like in many other resource-constrained countries around the world, have been slow to respond with appropriate alacrity. The high capital cost required to procure adequate and sustained volumes of drugs, upgrade the facilities, and decipher the confusion surrounding appropriate laboratory platforms was and remains prohibitive. This is compounded by poor human resource capacity, the legacy of the postcolonial demarcations, and bureaucratic civil service institutions crippled in many instances by blinding corruption.

In the last 3 years, in addition to the efforts of the WHO and United Nations, there have been effective critical support systems emerging, providing major impact, such as the Global Fund, the President's Emergency Plan for AIDS Relief (PEPFAR), technical support of NGOs such as the Clinton HIV/AIDS initiative, and the major lending institutions. These support mechanisms are and have been capable of providing the injection of funds and technical support required to empower some nations with the capacity to overcome some of these obstacles. Barbados, in an extraordinary demonstration of political foresight, seized on these opportunities to radically address the potentially disastrous consequences of a lethargic socio-political response to HIV/AIDS.

THE BARBADOS EXPERIENCE

Immediately after the UNGASS meeting on HIV/AIDS in June 2001, Barbados took an early and definitive stand by planning a multi pronged expanded program, instituting a special task force for implementing a full scale up program from scratch. Barbados, a country of 300,000 inhabitants, is significantly dependent on tourism and has a reasonable health infrastructure, and is ranked about 31 on the global human development index, the highest in the Caribbean region (7). However, despite this, it lacked the appropriate specialized laboratory and human resource capacity necessary to cope with an expanded HIV treatment and care program.

BASIS FOR THE TECHNOLOGY REQUIRED FOR CARE AND TREATMENT PROGRAMS

Soon after the isolation of the human immunodeficiency virus in 1983, its pathogenesis was soon elucidated. The culminating effect is both a quantitative and qualitative cell-mediated immune paralysis and the characteristic T helper cell lymphopenia (8).

Quite amazingly and by coincidence was the evolution of immunological assays capable of numerically analyzing subsets of cell populations with the help of monoclonal antibodies in the concept that we now understand as flow cytometry (9).

The drive to develop a clinically reliable test of the immunological consequences of the HIV-induced immunodeficiency became the panacea of diagnostic tools for assessing immune disorders, leukemia/lymphoma characterization and the science behind the vaccine programs.

By established agreed international convention, Flow Cytometry soon became the established platform for evaluating cellular immunological parameters. Following on from this was the evolution of protocols for determining the entrance of patients into an HIV treatment program for opportunistic infection prophylaxis and ART. The enumeration with reasonable accuracy of the T lymphocytes subset numbers, and more specifically the CD4 T helper lymphocyte, soon became established as the accepted surrogate marker of the cellular immune deficiency characteristic of HIV infection (10, 11).

Such technology and scientific culture was not only alien to the region of the Caribbean, but the expertise required was also even more remote.

BARBADOS PROJECT MANAGEMENT

Detailed multispecialist project management was required for the creation and coordination of such a facility aimed at the introduction of this state-of-the-art and rapidly evolving technology. The physical laboratory layout and plant to support such sophisticated equipment for the delivery and monitoring of ART simply had to be created. In June 2002, Barbados commissioned its dedicated HIV reference unit comprising a clinical structure and a dedicated laboratory equipped with four-color flow cytometers and real time polymerase chain reaction platforms for viral load estimations. A molecular biology suite that will be dedicated to the sequencing of the virus, to assist our team of care givers the luxury of intelligent prescribing, will soon come on stream.

Coordinating the project required dealing specifically with issues such as the process of equipment choices and procurement, developing relationships with vendors, staff recruitment, training, and capacity building. The need for high levels of quality control and standard operating practices was especially difficult in the light of limited regional expertise and manpower support. Barbados has long-term objectives of ultimately achieving international accreditation in the region and being a logistical support to the regional medical reference facility based in Trinidad. The emphasis of the unit in Barbados at the moment is on operational research focusing on cheaper and simpler algorithms for monitoring and providing support for a comprehensive, affordable, and sustainable program in the region. In this vein, it has strategically placed itself as a regional evaluating center for more affordable low throughput and more robust technologies that would suit the lower income territories of the Caribbean.

OUTCOMES

Three years after Barbados embarked on its expanded program of free access to treatment and care, there are now 900 registered patients in the facility, with about half of this number on active treatment with ART, and the laboratory is performing over 2,000 CD4 counts and viral loads respectively each year and rising. Within 2 years of starting this unit, there has been a 56% decline in AIDS related mortality, a 42% reduction in hospital admissions, and a significant reduction of maternal transmission. Barbados has already achieved its projected 5-year treatment targets at a net cost of US$ 46 per patient per year. Similar statistics are been achieved by other Countries in the Caribbean, such as Jamaica, Haiti, and Bahamas to name a few, but the overall statistics for the Caribbean as a whole is not encouraging. The coverage for those who need ART in the region is only 7%, which indicates that there is still significant progress to be made. The WHO 3 by 5 initiative (12), which sets global targets for the initiation of 3 million eligible people in low-income countries on ART by the year 2005, has long been considered to be seriously over-ambitious. Time has proved these critics to be right, but the kind of progress made by countries such as Barbados, Uganda, Senegal, and Brazil demonstrate that such targets are potentially attainable universally in all developing countries.

The global picture is also fairly dismal if we are going to rely on prevention, treatment, and care programs alone. Again, flow cytometry is rising to the challenge with the evolution of multicolor flow cytometry, which allows determination of functional capacity within a large number of lymphocyte subsets in response to potential vaccine candidates. The qualitative characteristics of an effective, broadly specific cell-mediated immunity that correlates with protection remain elusive. However, encouraging progress made by core labs like the NIH Vaccine Research Centre and the Dukes Human Vaccine Institute, utilizing multicolor (4–20-color) Flow Cytometry, could provide the critical information for designing long-lasting, disease-modifying vaccines (13). The current global estimation of people in need of ART is about 24 million. The best case scenario is that these people can be kept alive with ART till some effective immunotherapeutic option is available, and this indeed is the race against time for so many vulnerable populations.

LESSONS LEARNED AND A STRATEGY FOR RESOURCE CONSTRAINED COUNTRIES

The emphasis should remain on advocacy to mobilize political will. This remains the bedrock of any country or regional initiative if quality of life and statistical success are to be realized and the trends reversed. The countries that have achieved a plateau and for some a reversal of gradients in new HIV cases all have one thing in common and that is unquestionable political commitment at the highest level. Without this, there is little hope of success. New simpler platforms for evaluating immunological status and viral burden need to be further encouraged, developed, and evaluated. The pharmaceutical companies need to focus on volume-orientated marketing rather than exclusive prescribing. The issue of drug resistance is hovering over the heads of the scientific community like a dark cloud, while data management has not received the attention that it requires.

TECHNOLOGY TRANSFER

To enhance and facilitate the process of technology transfer, Barbados has been successful in organizing annual international workshops on flow cytometry and molecular biology, which has accelerated the process of technology transfer and capacity building, through networking.

The launching of a newly formed Caribbean Society of Cytometry and Clinical Analysis (CCAS) is aimed at fostering longer-lasting links with international established organizations to further create opportunities for stronger associations, exchange, and training. The Society will now be responsible for organizing the annual International Caribbean conference and workshops on flow cytometry and molecular biology.

SUMMARY

Despite the catastrophic global human suffering caused by HIV, the arrival of HIV on the scene has propelled the science of flow cytometry in all its parameters from enumeration precision and accuracy to quantitative flow cytometry, advanced vaccine development through multicolor flow cytometry, and the fusion of flow cytometry with molecular biology. At the same time HIV has definitely had the effect of accelerating the acquisition of technological capacity, laboratory infrastructure, strategic planning, and total quality management in the resource constrained environments. In parallel, there has been a dramatic rise in attempts to develop simpler, more robust, and cost-effective platforms for rural and resource-poor environments.

We are living in the era of emerging and reemerging viral epidemics and pandemics that threaten to invoke severe havoc and pain on a global scale. It is therefore essential that we understand that we are a global village and what attends in one corner of this planet will affect all. HIV is now in danger of being swamped by the new threats to mankind in the form of natural calamities and rapidly mutating viral infections. This is the same fate that malaria, tuberculosis, and poverty have befallen. It is however comforting that the infrastructures that are being put in place for HIV containment could be the same strategic infrastructure that would be necessary to combat new infectious threats to global security. We may soon be on the verge of experiencing a new phenomenon of “HIV donor fatigue,” but one hopes that the heart of humanity will never tire.