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EACS 2011: Multiple Regimens Are Used for First-Line HIV Treatment, but Outcomes Are Similar

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Initial antiretroviral therapy (ART) regimens vary widely according to patient characteristics and provider preferences, but most commonly used multi-class combination regimens appear to work about equally well, according to research presented at the 13th European AIDS Conference (EACS 2011) this month in Belgrade.

Luigia Elzi and fellow investigators with the Swiss HIV Cohort Study investigated factors that determine choice of first-line combination ART and their impact on patient outcomes. They looked at channeling bias, or the tendency to prescribe different types of regimens to people with different characteristics.

Some patients, for example, might prioritize the simplicity of a single-tablet regimen, pregnant women are advised not to use efavirenz (Sustiva) during early pregnancy due to risk of birth defects, and abacavir (Ziagen) and tenofovir (Viread) have different side effect profiles, the former being associated with cardiovascular events and the latter with bone and kidney problems.

This analysis included 1957 treatment-naive participants who started combination ART between 2005 and 2009 at 7 sites in Switzerland. Most (75%) were men, three-quarters were white, and the median age was 39 years; pregnant women were excluded. The median CD4 cell count was 245 cells/mm3 and 17% had been diagnosed with AIDS. Nearly 20% were coinfected with hepatitis B or C.

Results

  • The most common regimen was efavirenz/tenofovir/emtricitabine (the drugs in the Atripla single-tablet regimen), prescribed to 30% of participants.
  • 3 protease inhibitor-based regimens were next in line:

o      Lopinavir/ritonavir (Kaletra) plus tenofovir/emtricitabine (the drugs in the Truvada coformulation): 17%;

o      Atazanavir (Reyataz) boosted with ritonavir plus tenofovir/emtricitabine: 13%;

o      Lopinavir/ritonavir plus zidovudine/lamivudine (the drugs in Combivir): 13%.

  • Efavirenz plus abacavir/lamivudine (the drugs in Epzicom) was prescribed to 6% of patients.
  • Less commonly used combinations (3%-5%) included:

o      Lopinavir/ritonavir plus abacavir/lamivudine;

o      Nevirapine (Viramune) plus tenofovir/emtricitabine;

o      Efavirenz plus zidovudine/lamivudine;

o      Atazanavir/ritonavir plus abacavir/lamivudine.

  • About 7% of participants used other combinations besides these.
  • Prescription frequencies varied significantly across study sites.
  • In a multivariate analysis, compared with patients who received efavirenz/tenofovir/emtricitabine:

o      People who received lopinavir/ritonavir plus tenofovir/emtricitabine were significantly more likely to have a prior AIDS diagnosis (relative risk ratio [RRR] 2.82) and high viral load (HIV RNA >100,000 copies/mL) (RRR 1.53);

o      People in an opiate substitution program were more likely to receive atazanavir plus tenofovir/emtricitabine (RRR 2.67).

o      Women were more likely to get lopinavir/ritonavir plus zidovudine/lamivudine (RRR 3.86), likely due to concern about efavirenz if they became pregnant.

  • Efavirenz/abacavir/lamivudine was increasingly prescribed in more recent years, and people taking this regimen were less likely to switch drugs or stop therapy.
  • After 12 months of follow-up, 87% of patients achieved HIV virological suppression < 50 copies/mL.
  • CD4 T-cell counts increased by a median 174 cells/mm3.
  • No differences in virological or immunological outcome were observed among study sites.
  • Virological suppression was somewhat more likely with efavirenz/tenofovir/emtricitabine (92%) than with other regimens.
  • However, CD4 cell gains were higher with lopinavir/ritonavir plus zidovudine/lamivudine (210 cells/mm3).
  • In an intent-to-treat (switch=failure) analysis over the last year, the 2 most frequently prescribed regimens had similar virological response rates:

o      Efavirenz/tenofovir/emtricitabine: 75%;

o      Atazanavir/ritonavir plus tenofovir/emtricitabine: 73%.

"Large differences in prescription of initial combination ART but not in outcome among study sites were noted," the researchers concluded. "A trend towards tailored combination ART was observed."

"These differences were not fully explained by different patient characteristics," they added, suggesting that "[c]hoice of combination ART seems to be significantly influenced by physician's preference.

Investigator affiliations: University Hospital Basel, Infectious Diseases and Hospital Epidemiology, Basel, Switzerland; University Hospital Berne, Infectious Diseases, Bern, Switzerland; University Hospital of Zurich, Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland; University Hospital Lausanne, Infectious Diseases, Lausanne, Switzerland; University Hospital Geneva, Infectious Diseases, Geneva, Switzerland; Cantonal Hospital S. Gallen, Infectious Diseases, St. Gallen, Switzerland; Regional Hospital of Lugano, Infectious Diseases, Lugano, Switzerland.

10/28/11

Reference

L Elzi, S Erb, H Furrer, et al. Choice of Initial Combination Antiretroviral Therapy Regimen in Treatment-naive HIV- infected Individuals. 13th European AIDS Conference (EACS 2011). Belgrade, October 12-15, 2011. Abstract PS10/1.