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  17th European AIDS Conference
November 6-9
2019, Basel
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Response Differences Between First-Line Regimens in Large European Group
  17th European AIDS Conference, November 6-9, 2019, Basel
Mark Mascolini
Twelve-month virologic, CD4 count, and overall clinical responses differed in certain comparisons of contemporary antiretroviral classes in a 5102-person analysis of the European RESPOND cohort [1]. An adjusted analysis showed a worse composite treatment outcome with boosted protease inhibitors (PIs) than with integrase inhibitors. And people starting a nonnucleoside (NNRTI) had a worse 12-month CD4 response than those starting an integrase inhibitor. The researchers stressed, though, that this kind of analysis cannot eliminate confounding by indication--for example, the possibility that clinicians tended to prescribe NNRTIs for the healthiest people and boosted PIs for those with the most advanced HIV infection. And responses did not differ greatly by age, CD4 count, or viral load when antiretroviral therapy (ART) began.
RESPOND cohort investigators suggested randomized trials of new antiretrovirals offer limited insight into differences between regimens according to initial age, CD4 count, or viral load in real-world HIV populations. They aimed to compare short-term (12-month) virologic and immunologic (CD4) responses and longer-term clinical responses (new AIDS or death) in previously untreated people starting an integrase inhibitor (dolutegravir, elvitegravir, raltegravir, or bictegravir), a boosted PI (darunavir or atazanavir), or an NNRTI (efavirenz or rilpivirine) with two nucleosides/nucleotides. They looked specifically at subgroups defined by age (40 or younger, 41 to 50, over 50), CD4 count (below or above 350), severe immunosuppression (AIDS or CD4 count below 200), and viral load (below or above 100,000 copies).
The RESPOND team used logistic regression to compare virologic and CD4 responses 12 months after ART began. They used Poisson regression to compare rates of AIDS or death 14 days or more after ART began. Models adjusted for cohort, gender, race, HIV risk, time since HIV diagnosis, and for pretreatment CD4 count, viral load, age, AIDS, HBV, HCV, year starting ART, baseline date, and nucleoside/nucleotide backbone.
The researchers defined composite treatment outcome success as a 12-month viral load below 200 copies with no regimen change, AIDS, or death. Immunologic success meant a CD4 count above 750 or a 33% CD4 gain in people starting ART with more than 500 CD4s.
Among the 5102 ART-naive cohort members, 45% started an integrase inhibitor, 26% a boosted PI, and 29% an NNRTI. The most frequent nucleoside combinations were tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 72%) and abacavir/lamivudine (ABC/3TC, 18%).
People starting a booted PI were more likely to be women (23.4% vs 16.1% for integrase inhibitors and 16.9% for NNRTIs), have a higher viral load (43.8% above 100,000 vs 40.1% for integrase inhibitors and 26.0% for NNRTIs), and have a lower nadir CD4 count. People starting an integrase inhibitor began ART more recently (1/16) than those starting a boosted PI (8/13) or an NNRTI (2/14). Age did not differ substantially between the three treatment groups (older than 50, 19.1% for integrase inhibitors, 16.1% for boosted PIs, 15.3% for NNRTIs).
Overall, 57.9% of cohort members achieved composite treatment outcome success. That rate proved higher with NNRTIs (62.3%) and integrase inhibitors (61.4%) than with boosted PIs (48.3%). Multivariate logistic regression indicated significantly lower odds to composite success with a boosted PI than with an integrase inhibitor.
The overall immunologic success rate was 22.6%, and immunologic success was more frequent with integrase inhibitors (27.1%) than with NNRTIs (20.6%) or boosted PIs (18.1%). Logistic regression indicated significantly lower odds of immunologic success with NNRTIs than with integrase inhibitors. Overall incidence of a new AIDS diagnosis or death stood at 17.0 per 1000 person-years, and incidence was nonsignificantly higher with integrase inhibitors (21.2%) than with boosted PIs (18.1%) or NNRTIs (11.7%).
Composite treatment outcome success, immunologic success, and clinical failure did not differ substantially in the three age groups, by pretreatment CD4 count above or below 350, by pretreatment viral load above or below 100,000 copies, or by pretreatment severe immunosuppression (AIDS or below 200 CD4s) (all P > 0.05).
RESPOND investigators concluded that virologic, immunologic, and clinical outcomes are similar with different contemporary antiretroviral regimen regardless of age, immune suppression, or viral load when treatment begins. They suggested their findings provide "reassuring evidence that such subpopulations will have a similar response to ART, regardless of [antiretroviral] class.
1. Mocroft A, Neesgaard B, Zangerle R, et al, for the RESPOND study. Virologic, immunologic and clinical outcomes in antiretroviral treatment (ART) na´ve individuals in the RESPOND cohort collaboration. 17th European AIDS Conference, November 6-9, 2019, Basel. Abstract PE2/40.