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ICAAC 2014: Stribild Works Well Regardless of Age, Sex, or Race/Ethnicity

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The elvitegravir-based Stribild single-tablet regimen demonstrated good long-term efficacy and tolerability -- including fewer neuropsychiatric side effects than Atripla -- with consistent results across demographic subgroups, researchers reported at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy this month in Washington, DC. Other studies showed that Stribild is a good option for black patients either initiating or switching antiretroviral therapy (ART).

Stribild -- a 1-pill-once-daily regimen containing the integrase inhibitor elvitegravir, cobicistat as a booster, tenofovir, and emtricitabine -- is a recommended regimen for initial HIV therapy.

Richard Elion from Whitman Walker Health and colleagues performed a subgroup analysis of participants in Gilead Sciences' Phase 3 pivotal trials of Stribild known as Study 102 and Study 103.

This combined analysis included a total of 1408 people with HIV starting ART for the first time. Most (90%) were men, about 70% were white, nearly one-quarter were black, the mean age was 38 years, and the median baseline CD4 T-cell count was approximately 380 cells/mm3.

Participants were randomly assigned to receive Stribild or Gilead's older Atripla single-tablet regimen (efavirenz/tenofovir/emtricitabine) or boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (the drugs in Truvada).

Results

  • The primary analysis at week 48 showed that 89% of people taking Stribild, 84% taking Atripla, and 87% taking atazanavir had undetectable viral load (<50 copies/mL).
  • After 144 weeks on treatment, 79% of participants taking Stribild had undetectable viral load, as did 75% of those taking either Atripla or atazanavir.
  • Virological response rates for the 3 regimens were statistically similar regardless of demographic factors:

o   Age: 78%, 73%, and 69% among people <40 years vs 81%, 78%, and 81% among people >40 years.

o   Sex: 80%, 75%, and 76% among men vs 67%, 78%, and 62% among women.

o   Race: 81%, 79%, and 75% among white participants vs 75%, 68%, and 73% among non-whites.

  • Response rates were also similar regardless of baseline viral load or CD4 cell count:

o   HIV RNA: 81%, 74%, and 77% among those with <100,000 copies/mL vs 75%, 76%, and 71% among those with 100,000-400,000 copies/mL vs 80%, 83%, and 72% among those with >400,000 copies/mL.

o   CD4 count: 71%, 76%, and 76% among those with <200 cells/mm3 vs 81%, 75%, and 74% among those with >200 cells/mm3.

  • Emergent drug resistance was uncommon (<5%) in all treatment arms.
  • Stribild continued to be generally safe and well-tolerated at 144 weeks.
  • Dropout rates due to adverse events were similar in the Stribild, Atripla, and atazanavir arms (6%, 7%, and 8%, respectively).
  • Most side effects occurred with similar frequency across treatment arms.
  • However, efavirenz-associated neuropsychiatric symptoms such as insomnia, abnormal dreams, and dizziness were significantly more common in the Atripla arm compared with either the Stribild or atazanavir arms.
  • Jaundice and yellowing of the eyes was more common in the atazanavir group.
  • Fewer than 2% or patients in any arm discontinued due to kidney-related problems, a potential adverse effect of tenofovir.
  • Changes in serum creatinine occurred mostly within the first 4 weeks, then stabilized.

"Stribild had robust and durable efficacy through week 144," which was "consistent across demographics, HIV-1 RNA, and CD4 [count]," the researchers concluded. "Overall efficacy, safety, and tolerability support the use of Stribild as a first-line regimen in treatment-naive HIV patients."

Stribild for Black People with HIV

In a related study, David Hardy from the David Geffen School of Medicine and colleagues performed a post-hoc (after the fact) analysis of black or African-American participants, who made up about 30% of the treatment-naive participants in Study 102.

Black people account for a growing proportion of people with HIV and are more prone to kidney disease than whites, which could be a concern when using tenofovir-containing regimens.

There were 106 black participants (out of a total 348) assigned to receive Stribild and 91 (out of 352) assigned to receive Atripla in Study 102. More of the black patients were women (about 30% vs <10% of whites), but otherwise the groups were similar.

At 144 weeks, 78% of black patients taking Stribild and 66% taking Atripla had undetectable viral load, compared with 81% and 79%, respectively, of white patients. That is, Stribild showed a stronger advantage for black participants. A significantly higher portion of black participants reported achieving adherence >90% with Stribild than with Atripla (89% vs 74%), while adherence was the same in both treatment arms for white participants (94%).

Black people taking Stribild had significantly lower rates of side effects -- including neuropsychiatric symptoms -- and adverse events leading to drug discontinuation than blacks taking Atripla. No black participants stopped Stribild due to kidney-related adverse events.

"Stribild compared to Atripla is an efficacious, durable, well-tolerated, and safe treatment regimen for HIV-1-infected, treatment naive, Black adults," the researchers concluded.

Similarly, Joseph Gathe from Therapeutic Concepts in Houston and colleagues reported findings from an analysis of black patients who switched from non-nucleoside reverse transcriptase inhibitor (NNRTI)- or boosted protease inhibitor (PI)-based regimens to Stribild in the open-label STRATEGY-PI and STRATEGY-NNRTI trials.

They found that black participants who switched to Stribild from a NNRTI or boosted PI had "numerically higher rates of virological success at week 48," and there were no cases of virological failure. In STRATEGY-PI, 95% of blacks on Stribild vs 89% on a boosted PI had undetectable viral load; response rates for whites were 93% vs 87%, respectively. In STRATEGY-NNRTI, 95% of blacks taking Stribild vs 74% taking a NNRTI had undetectable HIV RNA; corresponding rates for whites were 94% vs 91%.

Again, Stribild was well-tolerated with infrequent discontinuations due to adverse events and no proximal renal tubulopathy.

"[Stribild] may be a viable switch option for virologically suppressed Black patients on a PI + 
[ritonavir] or NNRTI with [tenofovir/emtricitabine] who desire a regimen modification or simplification," the researchers concluded.

9/23/14

References

R Elion, K Squires, M Block, et al. Subgroup Analyses of 144-week Efficacy And Safety of Elvitegravir/cobicistat/emtricitabine/Tenofovir DF (EVG/COBI/FTC/TDF). 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014. Abstract H-644.

D Hardy, J Gathe, K Workowski, et al. Long-Term Efficacy and Safety of Single-Tablet Regimen EVG/COBI/FTC/TDF (STB) Compared to EFV/FTC/TDF (ATR) in HIV-1-Infected Treatment Naive, Blacks Subjects. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014. Abstract H-1001.

J Gathe, S Lewis, W Jordan, et al. Switch to E/C/F/TDF from PI+RTV or NNRTI plus FTC/TDF Maintains HIV Suppression at Week 48 and is Safe in Black Subjects. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014. Abstract H-1004.