In the Journals

Integrase inhibitors associated with improved viral suppression in HIV

The integrase inhibitor Tivicay combined with low-dose Sustiva was associated with higher rates of long-term viral suppression than standard-dose Sustiva in patients with HIV, data from a network meta-analysis indicated.

“The combination of [Atripla, Bristol-Myers Squibb/Gilead Sciences (efavirenz, tenofovir, and emtricitabine)] is the preferred option for first-line therapy, although a ritonavir-boosted protease inhibitor or an integrase strand transfer inhibitor-based regimen can also be used in a first-line regimen in patients with complex diseases or contraindications, or both,” Steve Kanters, MSc, of Precision Global Health and the School of Population and Public Health, University of British Columbia, and colleagues wrote. “Results of our analysis showed that [Tivicay, ViiV Healthcare (dolutegravir)] and [Sustiva, Bristol-Myers Squibb (low-dose efavirenz)] were not only more tolerable than [Sustiva, Bristol-Myers Squibb (standard-dose efavirenz)], but that they were also more effective, albeit with dolutegravir doing slightly better with respect to viral suppression efficacy and tolerability.”

To evaluate the safety and efficacy of available ART regimens among ART-naive patients with HIV, researchers conducted a network meta-analysis using 126 manuscripts from 71 trials, including patients in 161 treatment groups (n = 34,032). At 48 weeks, Kanters and colleagues reported, dolutegravir produced superior viral suppression vs. efavirenz (OR = 1.87; 95% credible interval [CrI], 1.34-2.64). Raltegravir also had better viral suppression than efavirenz (OR = 1.4; 95% CrI, 1.02-1.96). The drug with the “most protective effect,” the researchers wrote, was dolutegravir (OR = 0.26; 95% CrI, 0.14-0.47). Low-dose efavirenz also was more effective than standard-dose efavirenz (OR = 0.39; 95% CrI, 0.16-0.92). Kanters and colleagues did not report any conclusions about adverse effects, citing insufficient data.

In an accompanying editorial, Anton L. Pozniak, MD, and Andrew M. Hill, PhD, both of the St. Stephen’s AIDS Trust, Chelsea and Westminster Hospital, London, wrote that the dramatic price difference between generic ART and newer drugs may outweigh the benefits.

“Generic combination treatment with tenofovir, lamivudine and efavirenz is available in low-income countries for between US $110 and $184 per person-year,” Pozniak and Hill wrote. “The launch price for the patented combination of [Triumeq, ViiV Healthcare (abacavir, lamivudine and dolutegravir)] in the USA was $32,000 per person-year (average wholesale price).”

They also wrote that the meta-analysis “has a methodological issue, which limits the applicability of the results,” pointing to the SINGLE trial, in which researchers reported dolutegravir had a slightly higher virological failure rate than efavirenz at 144 weeks.

“National health authorities need to carefully assess how universal access programs for HIV prevention, testing, treatment and care can be achieved within realistic budgets,” Pozniak and Hill wrote. “Difficult decisions will need to be taken if we are to achieve the UNAIDS targets for antiretroviral treatment coverage.” – by Andy Polhamus

Disclosures: The researchers report no relevant financial disclosures. Hill and Pozniak report receiving consultancy payments from Bristol-Myers Squib, Cipla, Gilead Sciences, Janssen, Merck and ViiV Healthcare, though not connected with this editorial.

The integrase inhibitor Tivicay combined with low-dose Sustiva was associated with higher rates of long-term viral suppression than standard-dose Sustiva in patients with HIV, data from a network meta-analysis indicated.

“The combination of [Atripla, Bristol-Myers Squibb/Gilead Sciences (efavirenz, tenofovir, and emtricitabine)] is the preferred option for first-line therapy, although a ritonavir-boosted protease inhibitor or an integrase strand transfer inhibitor-based regimen can also be used in a first-line regimen in patients with complex diseases or contraindications, or both,” Steve Kanters, MSc, of Precision Global Health and the School of Population and Public Health, University of British Columbia, and colleagues wrote. “Results of our analysis showed that [Tivicay, ViiV Healthcare (dolutegravir)] and [Sustiva, Bristol-Myers Squibb (low-dose efavirenz)] were not only more tolerable than [Sustiva, Bristol-Myers Squibb (standard-dose efavirenz)], but that they were also more effective, albeit with dolutegravir doing slightly better with respect to viral suppression efficacy and tolerability.”

To evaluate the safety and efficacy of available ART regimens among ART-naive patients with HIV, researchers conducted a network meta-analysis using 126 manuscripts from 71 trials, including patients in 161 treatment groups (n = 34,032). At 48 weeks, Kanters and colleagues reported, dolutegravir produced superior viral suppression vs. efavirenz (OR = 1.87; 95% credible interval [CrI], 1.34-2.64). Raltegravir also had better viral suppression than efavirenz (OR = 1.4; 95% CrI, 1.02-1.96). The drug with the “most protective effect,” the researchers wrote, was dolutegravir (OR = 0.26; 95% CrI, 0.14-0.47). Low-dose efavirenz also was more effective than standard-dose efavirenz (OR = 0.39; 95% CrI, 0.16-0.92). Kanters and colleagues did not report any conclusions about adverse effects, citing insufficient data.

In an accompanying editorial, Anton L. Pozniak, MD, and Andrew M. Hill, PhD, both of the St. Stephen’s AIDS Trust, Chelsea and Westminster Hospital, London, wrote that the dramatic price difference between generic ART and newer drugs may outweigh the benefits.

“Generic combination treatment with tenofovir, lamivudine and efavirenz is available in low-income countries for between US $110 and $184 per person-year,” Pozniak and Hill wrote. “The launch price for the patented combination of [Triumeq, ViiV Healthcare (abacavir, lamivudine and dolutegravir)] in the USA was $32,000 per person-year (average wholesale price).”

They also wrote that the meta-analysis “has a methodological issue, which limits the applicability of the results,” pointing to the SINGLE trial, in which researchers reported dolutegravir had a slightly higher virological failure rate than efavirenz at 144 weeks.

“National health authorities need to carefully assess how universal access programs for HIV prevention, testing, treatment and care can be achieved within realistic budgets,” Pozniak and Hill wrote. “Difficult decisions will need to be taken if we are to achieve the UNAIDS targets for antiretroviral treatment coverage.” – by Andy Polhamus

Disclosures: The researchers report no relevant financial disclosures. Hill and Pozniak report receiving consultancy payments from Bristol-Myers Squib, Cipla, Gilead Sciences, Janssen, Merck and ViiV Healthcare, though not connected with this editorial.