Update on HIV Viral-load Assays: New Technologies and Testing in Resource-limited Settings

Carmen de Mendoza; Vincent Soriano

Disclosures

Future Virology. 2009;4(5):423-430. 

In This Article

HIV Viral-load Monitoring in Developing Countries

Over the last 10 years, the landscape of care and treatment of HIV-infected individuals has changed in most resource-limited settings facing an elevated AIDS burden. According to WHO, by June 2007 an estimated 3 million people were receiving combination antiretroviral therapy (cART) in low- and middle-income countries worldwide.[102] Trends in treatment scale-up have been particularly encouraging in sub-Saharan Africa.[30] In this region, the number of people receiving cART increased more than tenfold, from less than 10% to 25-50% between 2003 and 2007. These strides have been made possible through the availability of generic antiretroviral drugs and price reduction of patented medications. This increase in widespread availability of cART is ongoing and moving forward by increasing financial resources through programs such as 'Towards Universal Access to Treatment' promoted by WHO, UNICEF and UNAIDS.[102]

In contrast with the efforts to make a rapid scaling-up of antiretroviral medications possible in developing regions, the commitment of stakeholders to make diagnostic and monitoring HIV tests accessible has not been running in parallel. It has only been appreciated recently that the lack of adequate HIV monitoring may pervert the benefit derived from the widespread use of cART. Since HIV viral-load testing is the best tool to enable early detection of therapeutic failure, unrecognized virological failure along with selection and accumulation of drug resistance have been reported in subjects treated empirically and lacking periodic monitoring. Although primary drug resistance is still not a matter of concern and poor drug adherence is the main reason for treatment failure, it is reasonable to assume that things may become worse, as transmission of HIV drug-resistant strains will inevitably increase.

In patients with a plasma HIV viral load detectable within the first months of cART, the most frequent cause of virological failure is poor adherence to therapy. This is true anywhere and, therefore, early adherence interventions are crucial to enhance the rates of undetectable viremia with any first-line therapy. In this way, selection of drug resistance is minimized and the need for switching to second-line therapies is avoided. Since rescue regimens are generally much more expensive and difficult to access in developing countries, this consideration is particularly relevant for these regions. At this time, measurement of HIV viral load is the only biological tool available to recognize early virological failure and, therefore, periodic viral-load testing of HIV patients under cART is particularly needed in developing regions.

The benefit of making HIV viral-load testing accessible in developing regions where cART is rapidly scaling up, is also important for the early diagnosis of pediatric HIV infection.[31] It is well known that the number of infected women with childbearing age is particularly high in some developing countries. All newborns from HIV-infected mothers are HIV seropositive until 12-18 months of age, and currently, the best way to identify those babies who have been infected as early as possible is viral-load testing. This early diagnosis is critical to provide the opportunity to start cART as early as possible and prevent opportunistic complications in HIV-infected newborns.

In most resource-limited settings the decision to initiate cART in adults and adolescents relies on clinical and immunological assessment. In order to facilitate the rapid scale-up of cART programs and provide universal access to therapy, the WHO has emphasized the importance of using clinical parameters in deciding when to initiate cART. However, the value of clinical staging is improved by adding additional information, mainly the CD4 cell count.[104] Therefore, efforts to facilitate access to cART must be accompanied by laboratory improvements; CD4 counts and HIV viral-load measurements being the most important tests. Unfortunately, they are not widely available and will remain restricted owing to costs and accessibility.

This inability to perform CD4 counts and HIV viral-load testing in parallel will create new situations that Western countries are not familiar with. If treatment failure is defined on the basis of CD4 criteria, then the diagnosis of failure will often be later than using viral-load monitoring. Diagnosing treatment failure based on clinical or CD4 criteria alone will provide a great opportunity for the selection of drug-resistant viruses before changes in cART are made. In this regard, the success of second-line regimens might be lower than expected when changes are made in early virological failure, due to increasing class-wide drug resistance.

Finally, switching therapy when any virus is detectable (as recommended in industrialized countries where multiple individualized treatment regimens can be used) may be dangerous if viral-load testing is available but difficulties exist regarding access to drug-resistance testing or to antiretroviral drugs to be used in rescue regimens. Establishing the cause of treatment failure, particularly poor drug adherence, may be critical in this context. Moreover, viral-load thresholds for switching regimens other than detectability with current assays (< 50 copies/ml) should be evaluated and remain an area of research priority. Preliminary evidence suggests that virological failures in plasma in the range of 5000-10,000 HIV-RNA copies/ml can reliably provide quantitation values for viral load using DBS.[32,33,34]

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