The authors of this study note that the World Health Organisation treatment guidelines for HIV-1 infection recommend second-line combination antiretroviral therapy with a ritonavir-boosted protease inhibitor (either lopinavir or atazanavir) combined with at least two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs) if virological failure occurs with first-line combination antiretroviral therapy.However, there is uncertainty about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two NtRTIs.
The authors conducted a 96-week, phase 3b/4, randomised, parallel, open-label non-inferiority trial at 37 sites worldwide (including the UK) to compare the efficacy, safety, and tolerability of a new treatment regimen (ritonavir-boosted lopinavir plus raltegravir) with the current WHO-recommended standard of care (ritonavir-boosted lopinavir plus NtRTIs).
Adults with HIV-1 and confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly allocated (1:1) to either ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). Participants were stratified by clinical site and screening plasma viral load. The primary endpoint was the proportion of participants with plasma viral load of less than 200 copies per mL at 48 weeks after randomisation in the modified intention-to-treat population (defined as all participants who received at least one dose of study drug and attended at least one study visit after enrolment). The non-inferiority margin was set at 12%.
Overall 558 patients were enrolled, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1.8%, 95% CI −4.7 to 8.3), fulfilling the criterion for non-inferiority. The treatment was well tolerated - the most common adverse effects were gastrointestinal.
The authors note several limitations to their study, including:
- The open label design may have introduced some bias. However, they add that other study design factors (such as hard primary outcome and little loss to follow up) would have reduced this.
- At current prices, the NtRTI-free regimen is more expensive than the control regimen in low-income and middle income settings.
The authors of a related Comment article state that the findings “are important because they show that the WHO-recommended second-line treatment is an efficacious rescue regimen.” Whilst they also note some possible advantages of the raltegravir regimen, they acknowledge that the advantages are counterbalanced by the current higher cost of raltegravir, especially in low and middle-income countries.
In England, services for people with HIV infection are commissioned through NHS England (formerly the NHS Commissioning Board). Cost of HIV treatments may vary due to price negotiations with the manufacturers at a regional level. The British HIV Association has produced guidelines for the management of HIV infection in the UK and these cover treatment options following first line failure. The guidelines are NICE accredited.