UK HIV patients have high levels of primary drug resistance

The proportion of United Kingdom's HIV patients with primary resistance to anti-HIV drugs increased significantly between 1996 and 2003, according to data published on November 18^th in the online edition of the British Medical Journal. The investigators also found that the UK has a much higher rate of primary resistance than other European countries and the US, and that the risk of becoming infected with drug-resistant HIV was similar for gay men and Africans, the two groups most affected by HIV in the UK.

A separate joint European/Canadian study published in the December 15^th edition of the Journal of Acquired Immune Deficiency Syndromes also found that the proportion of individuals with primary drug resistance has increased over time, and that in 2003 13% of patients who had never taken anti-HIV drugs had resistance to at least one antiretroviral agent.

Although effective antiretroviral therapy has led to a significant reduction in levels of illness and death in HIV-positive individuals, there are concerns that the spread of drug-resistant virus could reduce the effectiveness of anti-HIV drugs. Investigators conducted a multi-centre survey involving blood samples obtained from 2300 HIV-positive individuals who had never taken anti-HIV drugs, sampled between 1996 and 2003. They aimed to describe the epidemiology of primary drug resistance in the UK; the number of cases seen each year; and to see if there was any relationship between primary resistance and demographic factors.

A total of 335 (14%) showed evidence of primary resistance to HIV drugs. Of these, 219 (9%) exhibited a high level of resistance to anti-HIV drugs and 116 samples (5%) medium level resistance.

The prevalence of resistance increased significantly over time. In 1996, 11% of tested samples showed signs of primary resistance, but by 2003 this had increased to 19% (p

A total of 233 samples (10%) were resistant to drugs from the nucleoside/nucleotide analogue class, 106 (5%) showed resistance to non-nucleoside analogues and 108 (5%) exhibited primary resistance to protease inhibitors.

Most samples (257, 11%) showed primary resistance to only one class of anti-HIV drugs, however 44 (2%) had primary resistance to two classes and 34 (1%) had primary resistance to all three main classes of anti-HIV drugs.

The investigators looked at the prevalence of primary resistance to individual anti-HIV drugs. They found that the nucleoside analogue with the highest prevalence of primary resistance was AZT (8%) and that 3TC had the lowest (3%). The prevalence of primary resistance to each of the individual non-nucleoside analogues was almost identical at 4%. Of the protease inhibitors, lopinavir had the lowest prevalence of primary resistance (2%) and nelfinavir the highest (4%).

Based on these findings, the investigators calculated that 9% of first-line anti-HIV treatment regimens prescribed in the UK would have reduced efficacy because the patient to whom they were given already had resistance to them.

Demographic characteristics did not seem significant. Primary resistance was equally prevalent in gay men (14%), heterosexual men (15%) and heterosexual women (16%). Rates of primary resistance were also broadly similar in whites (15%) and black Africans (17%). The investigators did however note that individuals who were infected with HIV subtype B, the type of HIV most common in western countries, had a slightly higher prevalence of primary resistance (14%) than individuals with subtype B – mainly found in Africa – at 10%. The investigators comment "African patients...had a similar prevalence [of primary resistance] to white patients. This finding is unexpected as most of the infections were likely to have been acquired in Africa, where access to antiretroviral therapy has been limited."

Individuals who had been recently infected with HIV (22%) had a statistically higher prevalence of primary resistance than those with longer-term HIV infection (14%, p = 0.006).

“The prevalence of primary resistance to antiretroviral therapy in people infected with HIV in the United Kingdom is high in all demographic subgroups and seems to be increasing”, write the investigators.

They compared the results from their study with those from other studies looking at the prevalence of primary drug-resistant HIV and found that the rate was considerably higher in the UK than in the US (7%), France (6%) and the rest of Europe (7%).

“By limiting the therapeutic options for a significant number of patients, the secondary epidemic of drug resistance represents a major clinical and public health problem”, conclude the investigators.

In a separate study, European and Canadian researchers looked at the proportion of patients newly infected with HIV who had primary drug resistance between 1987 and 2003. A total of 438 individuals were included in their analysis. They found that overall 10% of individuals had primary resistance, and that this increased from 2% pre-1996 to 13% in 2003.