Everyone with HIV who is prepared to take antiretroviral treatment should receive it, regardless of CD4 cell count, new draft British HIV Association (BHIVA) treatment guidelines recommend.
The new draft guidelines, published for consultation this week, say that anyone living with HIV who understands the commitment of treatment and is ready to start should receive treatment. The change – from a recommendation to start treatment before the CD4 cell count falls below 350 cells/mm3 to treatment for all – follows the results of the START trial, a keenly awaited international study of when to start treatment.
The START study showed that starting treatment at a CD4 cell count above 500 cells/mm3 reduced the risk of death or serious illness by 53% compared with waiting to start treatment until the CD4 count fell to 350 cells/mm3. Although the absolute risk of death or serious illness was small – 3.7% of people in the deferred treatment arm became seriously ill or died, compared to 1.8% in the immediate treatment group over three years of follow-up – the BHIVA guidelines committee concluded that the evidence now supports offering treatment to everyone prepared to take it.
Two other recent studies, the Temprano study and HPTN 052, also influenced the decision to offer treatment to all. Temprano, a study conducted in West Africa, showed that starting treatment at a CD4 cell count above 500 reduced the risk of serious illness and death by 44% when compared to starting treatment at lower CD4 counts.
The HPTN 052 study, carried out in sub-Saharan Africa, India, Brazil, Thailand and the United States, showed that early treatment – starting at a CD4 cell count between 350 and 550 – reduced the risk of clinical illness by 40% but did not significantly reduce the risk of death when compared to starting treatment at a CD4 cell count below 250 cells/mm3.
HPTN 052 also showed that earlier treatment reduced the risk of sexual transmission of HIV by 96%. That finding formed the basis for BHIVA’s previous recommendation that anyone living with HIV should be enabled to start treatment if they thought that it could reduce the risk of HIV transmission – and that all people living with HIV should be informed by their doctors of the evidence linking antiretroviral treatment to a reduced risk of transmission. Surveillance data presented by Public Health England earlier this year show that this recommendation coincided with a substantial increase in the proportion of people starting treatment at CD4 counts above 350 by the end of 2013 – but only 27% of people started treatment at a CD4 cell count above 500 in that year.
The updated guidelines continue to emphasise this evidence, and recommend that doctors should continue to discuss the potential for reducing transmission with all people living with HIV. People with HIV should be assessed for readiness to start treatment after diagnosis, but treatment initiation should only be considered urgent for people with AIDS-defining infections, serious bacterial infections or a CD4 cell count below 200 cells/mm3. People in any of these categories should start treatment within two weeks, the guidelines recommend.
Recently infected people – anyone diagnosed with primary HIV infection within 12 weeks of a previous negative test – should be encouraged to start treatment immediately in order to improve immune recovery, limit the size of the viral reservoir and limit the potential for onward transmission at a time of very high viral load. Anyone diagnosed with primary HIV infection who has a CD4 cell count below 350 cells/mm3, an AIDS-defining illness or neurological symptoms should also be encouraged to start treatment as soon as they can. Other people diagnosed soon after infection should be invited to consider starting treatment in the same way as any other person diagnosed with HIV – when they feel ready.
What to start with
The guidelines also make a further shift away from recommending efavirenz-based treatment as the standard regimen for first-line treatment. Efavirenz has been at the core of first-line antiretroviral treatment in the United Kingdom for nearly 15 years, and has been the preferred first-line option since 2008, but recent trial results have shown that some other agents are superior in some patient populations. Trials have also reinforced questions about the long-term tolerability of efavirenz.
Efavirenz has been downgraded to an 'alternative' choice for the first time. Instead, the guidelines now recommend that the first-line regimen should be based on either:
- an integrase inhibitor – either dolutegravir (Tivicay, also available in the combination pill Triumeq with abacavir and lamivudine), raltegravir (Isentress) or elvitegravir/cobicistat (Vitekta and Tybost, also available in the combination pill Stribild with tenofovir and emtricitabine);
a boosted protease inhibitor (either atazanavir/ritonavir or darunavir/ritonavir)
the new non-nucleoside reverse transcriptase inhibitor rilpivirine (Edurant, also available in the combination pill Eviplera with tenofovir and emtricitabine).
Doctors are recommended to ask all people taking efavirenz about sleep and mood at every clinic appointment, in order to identify people who might benefit from switching to a better-tolerated drug.
The preferred backbone for first-line treatment continues to be tenofovir and emtricitabine, with abacavir and lamivudine as an alternative where people do not have viral load above 100,000 copies/ml. Abacavir and lamivudine can be used at any viral load when combined with dolutegravir in the fixed-dose combination pill Triumeq, due to the high potency of dolutegravir. Abacavir is not suitable for use by people with a genetic profile which makes them hypersensitive to the drug, and everyone should be tested for the genetic marker HLA-B*5701 to screen out people who are likely to be hypersensitive before starting treatment with the drug. Abacavir should not be used in people with a high risk of cardiovascular disease, and tenofovir should not be used in people with stage 3-5 chronic kidney disease.
The guidelines committee states that where drugs are equivalent in terms of efficacy and safety for a specific patient population, cost should be a consideration in prescribing. Prescribing on the basis of cost should not be permitted to affect patient outcomes or quality of care, however.
The guidelines consultation runs until 17 July. You can submit comments here.