The era of viral load is here

The era of viral load is hereBy Sharonann Lynch - Viral load testing measures the amount of HIV virus (HIV RNA) in a person’s blood. It is the optimal method for identifying antiretroviral therapy (ART) treatment failure (defined as an HIV viral load greater than 1000 copies/mL), because it is more sensitive and has a higher positive predictive value than CD4 cell count and other clinical indicators.

By Sharonann Lynch

Viral load testing measures the amount of HIV virus (HIV RNA) in a person’s blood. It is the optimal method for identifying antiretroviral therapy (ART) treatment failure (defined as an HIV viral load greater than 1000 copies/mL), because it is more sensitive and has a higher positive predictive value than CD4 cell count and other clinical indicators.

Diagnosing treatment failure as soon as possible is important, so that HIV-positive people can switch to an effective second-line regimen that suppresses the virus and keeps them healthy. Viral suppression also benefits communities, since it significantly lowers the risk for HIV transmission. Viral load monitoring is more likely to keep people alive and in care than other testing. When used with counselling and other support services, it increases adherence to ART. The latest World Health Organisation (WHO) guidelines recommend that viral load testing occur six months after initiation of ART and every 12 months thereafter.

Expanding access to viral load monitoring will be crucial for achieving the third goal articulated in the UNAIDS ‘90:90:90’ treatment targets, which calls for 90% of people receiving ART to have durable viral suppression (defined as an HIV viral load below 50 copies/mL) by 2020.

A 2015 survey conducted by Médecins Sans Frontières (MSF) found that 47 out of 54 low- and middle-income countries recommended routine viral load monitoring for people on ART in their national HIV guidelines. Despite widespread adoption on the policy level, implementation of routine viral load testing remains limited. Barriers such as high prices, logistical challenges, and lack of awareness limit access to viral load monitoring, particularly in resource-limited settings.

Prices for viral load testing vary significantly between manufacturers and within countries. Countries must be able to accurately forecast demand over an extended period of time, so that paying for viral load testing is economically feasible. The largest initial expense is the testing equipment, which can be priced at up to US$200 000. Countries can avoid high up-front costs by either leasing equipment or participating in reagent agreement plans. These plans charge a fixed price per test, including equipment, maintenance and repairs. Costs are distributed evenly over time, and countries can adapt to new testing products as they become available. There are other expenses: Roche’s test has a global commercial ceiling price of US$9.40 per test, while the price of Siemens’ product ranges from US$54-72.

Increasing demand is an effective method for lowering prices, as it allows countries to take advantage of market competition. In South Africa, where viral load monitoring has already been rolled out, a successful competitive tender process was run that reduced the price per viral load test to under US$8. The price of viral load testing can be defrayed by savings from monitoring CD4 cell count less often, while access to viral load testing is expanded, although countries should be cautious about scaling back CD4 cell testing before viral load monitoring has been effectively rolled out. WHO guidelines suggest that monitoring CD4 cell count can be safely reduced or eliminated for people who are clinically stable on ART and who live in areas where routine viral load monitoring is consistently available. Eight countries so far have adopted this recommendation and eliminated routine CD4 cell testing for people on antiretroviral treatment.

Some of the logistical challenges to scaling up viral load monitoring can be addressed by new technology. Although plasma samples are the “gold standard”, they require strict temperature control and rapid transport to laboratories. This makes it difficult to implement plasma-based testing in settings with limited laboratory capacity and decentralized care systems, but dried blood spot (DBS) samples can be used to avoid these challenges. DBS is the best sample option for scale up in resource-limited settings, because samples are stable at ambient temperatures for long periods of time, are lightweight, and are easy to transport. Currently available DBS tests have lower specificity and sensitivity than plasma-based tests, and most testing platforms have not yet received regulatory approval for use with DBS, but improved products are expected in the near future.

Viral load testing is primarily performed by trained technicians in laboratories. Point-of-care and near point-of-care tests are becoming increasingly available. These eliminate the need to transport samples, and people can get their test results faster than with laboratory-based tests. But point-of-care tests can be more expensive, have lower throughput capacities, and require more training for health care workers in decentralized care settings.

No matter what type of test is used, a well-developed system for tracking and notifying people of their results in a timely manner is a crucial component of all testing initiatives.

The WHO recommends several strategies for scaling up routine viral load monitoring.

Countries with limited existing capacity can begin by using viral load tests to confirm suspected cases of treatment failure identified by clinical or immunological criteria. Viral load monitoring can then gradually be scaled up to routine use for all people on ART. Routine testing can also be phased in gradually, by targeting specific populations or geographic areas. For example, viral load testing can be implemented first in health facilities that have greater laboratory capacities, or can be selectively offered to high-risk groups such as children and pregnant women.

Routine viral load monitoring cannot become a reality without a significant investment in awareness and education. By itself, access to routine viral load monitoring does not guarantee effectiveness and utilisation, unless it is provided with best practices such as enhanced adherence counselling (EAC) for people with high viral loads. People living with HIV must have information about the meaning and importance of viral load monitoring and viral suppression, how frequently testing is required, and how viral load monitoring differs from CD4 testing, in order to create demand for viral load monitoring.

Education and training should also be provided to healthcare workers, to improve their knowledge of and motivation for providing routine viral load testing. Efforts to scale up viral load monitoring should include civil society organizations that raise awareness and influence donors and governments. To this end, the International Treatment Preparedness Coalition has developed an ‘Activist Toolkit’ to empower advocates to campaign for greater access to viral load monitoring.

A recent MSF report ( Making viral load routine) on implementation of the viral load treatment “cascade” across MSF-supported sites in four African countries confirms that further scale up is required. Coverage of routine viral load monitoring at these sites ranged from 32-91%, while rates of provision of EAC (57-70%) and the likelihood of tests being repeated after EAC intervention (23-68%) also varied. Rates of switching to second-line ART regimens after persistent high viral load results were low at all sites (10-38%), however higher rates were achieved at sites using point-of-care tests.

Ultimately, the effectiveness of any scale up strategy will be context-dependent and programs should be designed to reflect local capacities and challenges, including financial resources, health system infrastructure, disease burden, and populations. Collaboration between all involved stakeholders – including governments, donors, clinicians, people living with HIV and civil society – is required to overcome barriers and expand access to viral load testing for all people receiving HIV treatment.

The report ‘Making viral load routine’ can be found here

Sharonann Lynch is with the Médecins Sans Frontières Access Campaign.