British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapy (2006)

This summary document is an update to the full British HIV Association (BHIVA) Treatment Guidelines published in HIV Medicine in July 2005 (Volume 6, Supplement 2). Only the ‘What to start with’ and ‘Treatment-experienced patients’ sections have been completely rewritten. The tables of recommendations (Tables 1–7) have also been updated to include new data. Please refer to the full guidelines for more information. Since the last version of these guidelines there have been few new data relating to adherence to medication in general, or to highly active antiretroviral therapy (HAART) in particular. Studies continue to support a role for brief interventions including treatment-related education and individualized adherence problem-solving in increasing adherence (at least over the following months) [1,2]. A study looking at using long-term partners to support adherence showed a marked beneficial effect on adherence in the short term, but this was not sustained at 6 months [3]. In the Gilead 934 study, although adherence (measured by pill count) was statistically significantly higher in the once-daily arm vs. twice-daily, the clinical difference was small (3%) and may have arisen because of the poorer tolerability of the twice-daily arm rather than because of any benefit of once-daily dosing [4]. Research in the USA examined the costs in real terms of delivering a variety of adherence interventions over the first year of patient support. The majority of interventions were delivered by nurses. Median direct annual cost was $420 (range $60–700) per patient; 66% of this was attributed to staffing but this also included $72 per annum for patient incentives, which are unlikely to be deployed in the UK. Although it is difficult to extrapolate these costs to NHS services in the UK, the absolute cost of adherence interventions appears to be relatively low, and slightly less than that of a genotype resistance test [5]. No new data have emerged in the past year to change the view of the Committee that, if antiretroviral therapy is started in the context of primary HIV infection, it should normally only be in the setting of a clinical trial (e.g. the MRC SPARTAC study [6]). Decisions on when to start treatment are based on an assessment of the risk of disease progression over the medium term if treatment is not started (e.g. using data from the CASCADE collaboration [7]), vs. the potential risks of starting treatment earlier (toxicity and resistance). The risk of disease progression is determined largely by the CD4 cell count, plasma viral load and the age of the patient. No new data have emerged since the previous guidelines to alter the Committee's view that treatment should start before the CD4 cell count has fallen to below 200 cells/μL. This is because of the higher risk of death or disease progression in patients who delay starting treatment until their CD4 cell count has fallen to this level, and the reduced efficacy of HAART when introduced at a count of <200 cells/μL in some studies. The implication of this is that earlier diagnosis of infection remains paramount; this is only likely to be achieved by much more widespread and normalized use of HIV antibody testing [8]. In patients with counts above this level, the risk of disease progression without therapy should be considered. Therapy should be started if the patient wishes to start, the medium-term risk of disease progression is high (e.g.>2–4% in 6 months) and the likelihood of harm as a result of drug toxicity or the selection of resistant virus is considered to be low. This is likely to mean that the majority of patients with CD4 counts >350 cells/μL should continue to defer treatment. Although cohort studies [9–11] have consistently shown that the risk of disease progression in this group tends to be lower for up to several years if therapy is started earlier, this is at the cost of significant drug toxicity, necessitating drug switching or stopping therapy in a significant minority [9], and the absolute risk of disease progression in this group remains very low. Other cohort studies (albeit in patient groups using regimens that might not be recommended currently [12,13]) have demonstrated that selection of drug-resistant virus occurs in 25% of patients after 2–3 years, suggesting that deferral of initiation may preserve future treatment options. Patients randomized to the drug conservation (DC) arm (i.e. intermittent therapy) of the SMART study [14] had a significantly increased risk of opportunistic infection or death after 16 months of follow up compared to those in the virological suppression (VS) arm (i.e. continuous therapy). Importantly, this benefit was seen across all CD4 cell count strata, not only in those with a nadir CD4 count of <350 cells/μL. These data have been interpreted as evidence that drug treatment should be started at an earlier stage than is currently the case. However, of the of disease progression in the that the absolute risk of disease progression remains relatively in the arm of the study per year compared to in the This is with data from cohort and as not evidence to change the recommendations of the 2005 this the evidence that there is a continuous in the risk of disease progression and death in patients as the CD4 cell count and that on starting therapy to be the and risks in patient. Patients in the arm were also to have much higher of and disease than were seen in the this is to the effect of HIV infection, this be a for earlier the tolerability and toxicity of therapy and the risk of resistant virus with therapy it to starting therapy earlier than (i.e. earlier in the CD4 count and above counts of cells/μL in as those with higher viral and those with as or virus is evidence from cohort studies that the very in and of seen in the over the last years with the of in treatment have to patients of the of a is a viral load of months of starting therapy and this of the viral a of has been to be in the majority of by from start of to this is with to viral load below A viral load above after the initiation of therapy should over adherence or as reduced drug or primary drug HAART regimens should be individualized in to the adherence and to potential long-term toxicity and to any likely The cost of the should also be considered. guidelines have been by the of published data to HAART based a or is there have been only data on efficacy Studies have shown the of regimens over and regimens A trial a currently recommended with in patients has demonstrated on the of an HAART over This from a lower of virological in the with significant difference the in resistance and seen in the In a study with has demonstrated the of twice-daily at all CD4 cell count and viral load is to the to the and to risk for virus and In including and drug use should be as as and the potential for The and in terms of toxicity, and potential are In view of these the Committee that HAART should be the for However, it be that any drug be to the patient in including primary a is This remains a recommended a of the and as as currently in that patients should continue to be and to in clinical to these regimens have been with data for years have the of and of long-term toxicity and is the for However, is not a drug that is by all patients and the to be to patient before starting per of 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