The Stribild single-tablet regimen matched
both Atripla and boosted atazanavir (Reyataz) in efficacy amongst people age
50 and older, who responded as well as younger patients, researchers reported at the recent
53rd Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC) in Denver. Related studies showed that Stribild had durable efficacy through
three years and causes fewer central nervous system (CNS) side-effects than Atripla.
While modern antiretroviral therapy
is safe and highly effective, there is always room for new drugs that are more
convenient or better tolerated. The four-in-one Stribild pill
contains the HIV integrase inhibitor elvitegravir, the boosting agent
cobicistat (approved by the EMA last week as a stand-alone drug with the brand
name Tybost) and tenofovir and emtricitabine (the drugs in Truvada).
Joel Gallant from the Southwest
Care Center in Santa Fe presented findings from an analysis of the safety and
tolerability of Stribild in older individuals, who make up a growing proportion
of the HIV population in Europe and the US.
As reported at the
International AIDS Society Conference on HIV Pathogenesis, Treatment and
Prevention this past July, Gilead Sciences' phase 3 Study
102 showed that that Stribild was non-inferior to Atripla (efavirenz/tenofovir/emtricitabine)
at 96 weeks, with 84 vs 82% of previously untreated patients, respectively,
having undetectable viral load (<50 copies/ml). Likewise, Study 103 showed
that Stribild worked as well as ritonavir-boosted atazanavir plus Truvada, with 83 vs 82%, respectively,
having undetectable HIV RNA.
Gallant's analysis compared response
rates and side-effects between people age 50 and older and those younger than
50, using 96 week data from these two trials. In Study 102, 49 people (14%) randomly
assigned to receive Stribild and 56
(16%) assigned to Atripla were age 50
or older. In Study 103, 48 (14%) randomised to Stribild and 48 (14%) on atazanavir were in the older age group.
In both studies, about 90% of
participants were men, between two-thirds and three-quarters were white and the
mean CD4 cell count was approximately 375 cells/mm3.
In Study 102, 82% of participants older
than 50 had undetectable viral load at week 96 in both the Stribild and Atripla
arms. Within the younger group, rates were 85% and 81%, respectively, not a
significant difference. One older person in each treatment arm developed drug resistance
during the first year, but no additional patients did so during the second
Response rates were also comparable
in Study 103: 90% of people over 50 achieved undetectable viral load with both Stribild and boosted atazanavir. In the
younger group response rates were 82 and 81%, respectively. In this study, no older
patients developed resistance during either the first or second year.
Older patients did see somewhat
smaller CD4 cell gains. In Study 102, CD4 cells increased by 233 cells/mm3 with
Stribild and 250 cells/mm3
with Atripla at 96 weeks in the over 50
group, compared with 305 and 278 cells/mm3, respectively, in the
younger group. In Study 103, gains were 226 cells/mm3 with Stribild and 231 cells/mm3 with
atazanavir in the older group, and 261 and 266 cells/mm3,
respectively, in the younger group.
Turning to side-effects in Study 102,
in the older group there was significantly less dizziness and fewer abnormal
dreams amongst Stribild recipients
compared with Atripla recipients. In
the younger group, Stribild again
caused less dizziness and fewer abnormal dreams, but also significantly less
rash and more nausea. Looking only at
those taking Stribild, diarrhoea was less common amongst older compared with
younger patients, but none of the other side-effects differed significantly by
In Study 103, there were no statistically
significant differences in adverse events between older recipients of Stribild
vs boosted atazanavir. In the younger group, Stribild recipients had
significantly less yellowing of the eyes (a sign of elevated bilirubin) and
less diarrhoea, but more back pain, than atazanavir recipients. Within the
Stribild arm, older people had slightly less nausea but significantly more
depression than younger patients.
Older and younger people had similar
serum creatinine levels at baseline and experienced similar changes at 96 weeks
of treatment. In both age groups, however, increases were higher with Stribild (older 0.14-0.16 mg/dl; younger
0.12-0.13 mg/dl) than with Atripla
(older 0.05 mg/dl; younger 0.01 mg/dl) or atazanavir (older 0.12 mg/dl; younger
Total cholesterol, LDL ('bad')
cholesterol and HDL ('good') cholesterol increased significantly less with Stribild than with Atripla among younger patients. Increases in total cholesterol, LDL
and triglycerides were also were also smaller with Stribild in the older group,
though here there differences did not reach statistical significance due to
small numbers, Gallant noted. In contrast, cholesterol levels rose more with Stribild than with boosted atazanavir in
both age groups, though differences again were not significant.
People age 50 and older "had
high and similar rates of virological suppression as subjects age <50
years," the researchers concluded. Median CD4 cell increases were similar
with all three regimens, but were smaller for older patients.
Older people had "blunted" immune recovery indicated by "less
pronounced gains" in CD4 cells across the board, Gallant explained.