Good virological outcome in patients starting HIV therapy in the UK

The overwhelming majority of patients starting antiretroviral therapy for the first time have an undetectable viral load after six months of treatment, research presented to the autumn conference of the British HIV Association showed. This outcome is in line with UK HIV treatment guidelines.

The audit of over 100 centres offering anti-HIV care showed that patients with and without baseline resistance to antiretroviral drugs were equally likely to achieve an undetectable viral load.

But the results showed that the majority of patients initiate therapy when their CD4 cell count is below the 200 cells/mm³ threshold specified in current treatment guidelines, and fewer than 10% of patients started treatment when their CD4 cell count was 350 cells/mm³ or above, the level at which many doctors now think treatment should be started.

Every year the British HIV Association conducts an audit to determine adherence to treatment guidelines in HIV treatment clinics across the UK. In the summer of 2006 questionnaires were distributed to treatment centres across the UK to find out the proportion of patients achieving a viral load below 50 copies/ml (an undetectable viral load) six months after starting anti-HIV therapy.

Questionnaires were returned by 133 centres, including data for 1,170 patients. Over half these patients, 54%, were male, 49% were black African, 7% were black Caribbean, 38% were white and 17% were pregnant when they started anti-HIV therapy.

Despite clear guidelines that anti-HIV therapy should be started before a patient’s CD4 cell count falls to 200 cells/mm³, the audit showed that 60% initiated antiretroviral treatment when their CD4 cell count was below this level. Furthermore, late diagnosis of HIV infection could not explain why so many patients were starting treatment late, as a third of patients with a CD4 cell count below 200 cells/mm³ had been in HIV care for six months or more when they finally started treatment.

Only 10% of patients started treatment when their CD4 cell count was 350 cells/mm³ or higher. There is evidence that starting HIV treatment at this CD4 cell threshold, rather than waiting until the current 200 cells/mm³ trigger, is associated with better long-term immunological outcomes and a lower risk of some serious, non-HIV-related illnesses.

What’s more the audit revealed that the only reason why patients were starting treatment at the 350 cells/mm³ point in 2006 were the presence of symptoms associated with HIV infection or pregnancy.

British HIV treatment guidelines recommend that all patients should have a test to check for the presence of drug-resistant HIV before starting anti-HIV treatment. Such tests were performed on 72% of patients (although the actual percentage could be higher as there were no details of resistance testing for 7% of patients).

Of the patients who were tested, 94% had no drug resistance, 5% had resistance to one class of antiretrovirals, and 1% had multi-class resistant HIV.

Questions were asked about the drugs included in initial antiretroviral therapy. The most commonly used nucleoside reverse transcriptase inhibitor (NRTI) backbone was 3TC (lamivudine, Epivir) with abacavir (Ziagen). These two drugs are available in a once-daily combined pill, Kivexa and were taken by 35% of patients. The investigators think that the popularity of this backbone may reflect the widening use of HLA testing to monitor for a gene that is associated with a hypersensitive reaction to abacavir.

The next most popular NRTI backbone was FTC (emtricitabine, Emtriva) with tenofovir (Viread), available in a once-daily combined pill, Truvada. This was taken was 34% of patients initiating therapy.

Both Kivexa and Truvada are recommended for treatment-naïve patients in current UK treatment guidelines. The use of AZT (zidovudine) is now discouraged because of its association with fat loss, and the audit showed that the drug is now rarely prescribed to patients starting anti-HIV therapy, its use generally being restricted to special circumstances, such as pregnancy (AZT has been shown to be effective at reducing the risk of mother-to-child transmission of HIV).

As regards the choice of third drug, non-nucleoside reverse transcriptase inhibitors (NNRTIs) were preferred to boosted protease inhibitors, with 53% of patients starting therapy with efavirenz (Sustiva), 17% with nevirapine (Viramune), and 16% with Kaletra (lopinavir/ritonavir).

The primary aim of the audit was to see what proportion of patients had an undetectable viral load six months after starting treatment.

Overall, 68% of patients had this outcome. When the investigators restricted their analysis to patients who were still on anti-HIV therapy six months after starting, the proportion with a viral load below 50 copies/ml increased to 84%.

Small regional centres are providing care to an increasing proportion of HIV-positive patients in the UK. The audit showed patients who received their care at the smallest clinics (under 50 patients) were just as likely as those who were treated at the largest clinics (over 500 patients) to achieve an undetectable viral load at six months (88% vs. 84%).

Baseline demographics did not affect six-month virological outcome, with identical proportions (74%) of black and white, male and female patients having an undetectable viral load at this time.

Nor was six month outcome affected by the presence of resistance at baseline with 75% of patients without resistance having a viral load below 50 copies/ml as did 75% of resistance with baseline resistance. Patients who did not have a resistance test were slightly less likely (72%) to have an undetectable viral load after six months of treatment.

But the investigators did find that patients with lower baseline CD4 cell counts were less likely to have an undetectable viral load after six months. Although of 80% of patients who started treatment with a CD4 cell count above 200 cells/mm³ had a viral load below 50 copies/ml, this fell to 70% of patients who initiated treatment when their CD4 cell count was below 100 cells/mm³, with only 65% of patients whose CD4 cell count was below 50 cells/mm³ having an undetectable viral load at six months.

Reflecting the increasing availability of easier- to-take antiretroviral drugs, the investigators found that 85% of patients had no reported adherence problems, 11% some problems and 3% substantial problems.

Hepatitis coinfections are an increasingly important cause of illness and death in HIV-positive patients and UK guidelines recommend that all patients should be monitored for the presence of hepatitis B and C. The audit showed that 5% of patients starting antiretroviral therapy were hepatitis B-infected. However, 6% were untested for the infection. Some antiretroviral drugs also have activity against hepatitis B, but it is recommended that these drugs should be used in combination to reduce the risk of hepatitis B developing resistance to them. Nevertheless, the audit showed that a quarter of hepatitis B-infected patients were taking 3TC in their antiretroviral therapy without tenofovir (which also works against hepatitis B) and were therefore risking the emergence of hepatitis B-resistant virus.

Hepatitis C was found in 3% of the 95% tested for the infection.

The audit revealed that, on the whole, patients were being well-monitored, with 46% having a viral load test within four weeks of initiating therapy, 74% within 42 days and 85% within 56 days. But there was concern that about 10% of patients only had one viral load test in their first six months of treatment. By contrast, it appeared that 30% of patients were having their CD4 cell count and viral load monitored on more than three occasions. The audit investigators thought that this could be wasting resources.