HIV treatment responses in everyday care matching clinical trial levels

Patients receiving routine HIV care through a large US hospital had treatment responses that matched responses rates seen in recent clinical trials, indicating that very high rates of undetectable viral load are achievable in everyday clinical care, US investigators report in the February 15^th edition of Clinical Infectious Diseases.

They found that the two groups of patients were equally likely to have an undetectable viral load a year after starting triple-drug antiretroviral therapy and that their increases in CD4 cell count were also comparable.

Randomised controlled trials are a cornerstone of evidence-based medicine.

However, patient outcomes in routine clinical care are often poorer than those seen in clinical trials. It is thought that selection and volunteer bias may contribute to this.

Little is known about the comparative efficacy of modern antiretroviral treatment when started as part of a clinical trial or during routine care.

Investigators from the University of Alabama at Birmingham 1917 HIV/AIDS Clinic therefore designed a retrospective study that involved 570 patients who started HIV treatment between 2000 and 2006.

Because clinical trials “are ingrained in the culture of HIV care at many treatment centres”, and provide a means of accessing treatment and care, they hypothesised that they would find no selection or volunteer bias. Therefore, they anticipated that outcomes would be similar between patients starting treatment as part of a study, and amongst patients who initiated therapy during routine care.

They therefore compared viral load and CD4 cell count levels six and twelve months after HIV treatment was initiated.

Information was also obtained on factors that could contribute to treatment outcomes. These included baseline viral load and CD4 cell count, mental health status, drug and alcohol use, and sociodemographic characteristics.

HIV treatment was initiated during a clinical trial by 121 patients, and 86 of these patients did so during a randomised-controlled trial.

Patients who started therapy during a trial were more likely than those who did so during routine care to have a CD4 cell count above 200 cells/mm³ (61% vs. 40%, p

In addition, black patients were significantly less likely to start treatment during studies than routine care (54% of study population, 36% clinical trial vs. 59% routine care, p

After six-months, 66% of those starting treatment during a trial and 71% of those who did so during routine care had an undetectable viral load (below 50 copies/ml).

Virological outcomes were also comparable after twelve-months of therapy (67% vs. 73%).

Statistical analysis showed that there was no significance difference between the two groups of patients in virological outcome at either time point.

Next the researchers conducted further “sensitivity” analyses. It was only when they took missing data to mean virological failure that an inferior outcome at twelve months was seen amongst patients starting therapy as part of routine care compared to those doing so during a trial (OR = 2.10; 95%CI, 1.21-3.66).

The investigators believe that this finding is because individuals starting treatment during routine care were more likely to have missing viral load values than those who participated in a study (28% vs. 11%). They note that patients who miss appointments during studies are “aggressively” pursued.

There was no difference in six- and twelve-month gains in CD4 cell count between the two groups of patients.

However, the researchers did find that virological outcomes were poorer amongst black patients and those who did not have private health insurance.

They write, “limited access to health care and increased frequency of missed clinic appointments may contribute to the poor clinical outcomes observed among black patients with HIV infection; these factors may also impact on the availability of laboratory measures.”

Noting the association between outcome and health insurance status, the investigators comment, “these findings identify another vulnerable and underserved group at risk of worse health outcomes.”

The researchers acknowledge that their study was limited by its retrospective, single-site design.

Nevertheless, they conclude, “similar first-year responses were observed in treatment-naïve patients who started antiretroviral therapy in clinical trials and in those who started antiretroviral therapy in routine care.”