Viral load testing: once a year proves adequate in lower-income Asia study

Viral load testing once or twice a year had the same impact on patient health outcomes as more frequent testing, Rebecca Oyomopito and colleagues reported in a study of over 2300 patients from 17 sites across the Asia-Pacific region published in the March online edition of the journal HIV Medicine.

However, a 35% increased risk of severe symptomatic HIV disease and death was reported in sites with less than once-yearly viral load testing.

Increased access to antiretrovirals in resource-poor settings has not led to a corresponding increase in access to diagnostic tests to monitor viral load and CD4 cell counts, which are important tools in managing disease progression.

Viral load measures can alert a health worker to possible non-adherence, treatment regimen failure and HIV drug resistance. CD4 cell counts provide information on the strength of the immune system. International patient management guidelines use these measures to determine the best times to start or change treatment and monitor the response to treatment.

Cost, space, logistics, an absence of sufficient and adequately trained health care workers as well as the lack of water and interrupted supply of electricity means such tests are not as widely available in resource-poor settings as they are in resource-rich ones.

Little information on what effect the lack of diagnostics has had on patient health outcomes led the authors to look at this within the context of clinical resources (country income together with site-reported frequency of CD4 cell count and viral load tests).

The authors analysed the data of 2333 (69.7%) HIV-infected patients from the TREAT Asia HIV Observational Database (TAHOD), a multicentre prospective cohort of HIV-infected patients. Not all in the database had started ART. So the sample size included only those having started antiretroviral therapy, with any combination of three or more antiretrovirals since 2000 with at least one clinical visit or result recorded in the database following the start of ART.

The seventeen clinical sites, representative of the region, were categorised based on the World Health Organization (WHO) critera (gross national income per person) into high (upper-middle and upper: more than US$ 37005 and low (lower-middle and lower: equal to or less than US$ 37005) income sites.

Sites were also classified according to how often patients were monitored. There were three categories for viral load testing: at least three times a year, once or twice a year and less than once a year; and two categories for CD4 cell counts: at least three times a year and less than three times a year.

Disease progression was described as an AIDS-defining illness or death, whichever came first. Follow-up began at the start of ART. Surrogate endpoints included suppression of viral load to less than 400 copies/ml and change in CD4 cell count from baseline to 12 months after the start of ART.

Analysis of the 2326 (99.7%) patients with a median of 2.4 person-years (IQR: 1.2-3.7 person years) of retrospective and prospective follow-up showed significant higher rates of disease progression only where less than annual viral load testing took place (HR 1.4; p = 0.032).

Less than annual viral load testing also showed reduced odds of viral suppression (OR 0.30; p = 0.011). 33.7% (785) patients were included in viral load suppression analyses. The authors believe this reflects an individual site’s lack of capacity to identify for viral load testing those at high risk of disease progression, a challenge in resource-poor settings.

Previous diagnosis with an AIDS-defining illness (HR 1.4; p = 0.003), lower CD4 cell counts before starting ART as well as co-infection with hepatitis C virus (HR 1.8; p =0.011) were also predictive of higher rates of disease progression, as other studies have also shown. These findings are also comparable to sites where less than annual viral load testing took place.

Of the 1120 (48.2%) with CD4 cell count change (baseline and 12 month after start of ART) smaller increases were associated with being over 40 years of age as well as injecting drug use.

The authors note that possible bias should be considered as only what has been measured is included. So missing baseline CD4 cell counts and viral load counts may have added bias to the estimates. Consequently they note there may be over-or under-estimation of the proportion of patients virologically suppressed.

Findings show that even with viral load testing patients may be kept on failing regimens since no other options exist. Resistance may then develop which is then transmitted to others. Or, clinicians see that a patient is failing clinically and choose not to perform viral load testing because of scarce resources and no other treatment options.

The authors found that where less than annual viral load testing is available the risk of disease progression and death is the greatest.

However, there was no significant difference in disease progression between once or twice a year viral load testing and testing three times or more a year. Best practice in Europe, North America and Australasia is to test frequently in the first year of treatment, and then to test two to three times a year.

The authors conclude “our findings emphasize the need to partner the expanded international access to antiretrovirals with appropriate levels of viral load diagnostic testing and to address the critical lack of second- and third-line treatment regimens in resource-limited settings.”