HIV9: More Data Demonstrate Similar Efficacy of Abacavir and Tenofovir

As previously reported, ACTG study 5202 was partially halted this past March after interim results showed that among treatment-naive patients with a high baseline HIV viral load (> 100,000 copies/mL), abacavir/lamivudine (the drugs in the Epzicom coformulation pill) did not suppress HIV as well as tenofovir/emtricitabine (the drugs in the Truvada pill) when both were used in combination with either efavirenz (Sustiva) or ritonavir-boosted atazanavir (Reyataz). Four cohort studies presented at the recent 9th International Congress on Drug Therapy in HIV Infection in Glasgow provided further evidence regarding the relative efficacy of the abacavir/lamivudine and tenofovir/emtricitabine backbones. 

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Advanced Liver Disease in People with HIV

As HIV positive people live longer due to effective antiretroviral therapy, liver disease has become an increasingly important cause of illness and death in this population.

In some cases, advanced liver disease in people with HIV is related to coinfection with hepatitis B or C virus (HBV or HCV), certain antiretroviral drugs are known to cause liver toxicity, and in other cases the cause of liver disease is unclear. Three presentations at the recent 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow discussed end-stage liver disease (ESLD), advanced liver fibrosis, and severe portal hypertension in HIV-infected individuals.

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HIV9: Modern HAART Is Associated with Better Adherence and Greater Efficacy than Older Regimens

It is clear that treatment outcomes have dramatically improved since the introduction of effective combination antiretroviral therapy in the mid-1990s, and since then HAART efficacy has improved over time as new and better drugs have been developed. But the factors that contribute to this improved treatment success are not yet fully understood. To shed further light on this issue, Italian investigators retrospectively analyzed the efficacy of first-line regimens in 1998 and in 2006. Results were presented last week at the 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow, Scotland.

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CD4 Cell Count Improves with HAART-especially Protease Inhibitors-even if Viral Load Is Not Fully Suppressed

A majority of people currently being treated with combination antiretroviral therapy (ART) live in resource-limited settings, where it is common for patients to remain on virologically failing regimens, typically containing a non-nucleoside reverse transcriptase inhibitor (NNRTI).

As reported at the recent 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow, Scotland, Andrew Phillips, Amanda Mocroft, and colleagues with the EuroSIDA study aimed to identify the viral load level at which CD4 cells begin to decrease significantly in patients on ART, as well as factors associated with changes in CD4 count.

The analysis included 7231 patients contributing a total of 58,929 CD4 slopes (median 6 per person). CD4 slopes were calculated from 3 consecutive CD4 cell measurements performed while viral load was stable (defined as < 0.5 log10 copies/mL difference between the highest and lowest viral loads). Slopes were calculated over a median 6.6 months.

Results

• Those with 500-999 copies/mL experienced a consistent CD4 cell decrease, ending up almost 75 cells/mm3 below the first measurement.

• Patients on combination ART had more favorable -- that is, more positive or less negative -- mean CD4 slopes than those off therapy at any viral load level.

• Among treated patients, after adjusting for confounding factors, regimens containing a single protease inhibitor (PI) (mean CD4 slope 43 cells/mm3) or a ritonavir-boosted PI (47 cells/mm3) were associated with more positive CD4 slopes than NNRTI-based regimens (31 cells/mm3) or triple-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) regimens (30.2 cells/mm3) (P < 0.0001).

"The results from our study would suggest that some treatment with combination ART is better than none, but also that better CD4 count increases are obtained by using a PI or ritonavir-boosted PI-based regimen than by using an NNRTI-based regimen," the investigators concluded.

Based on these findings, they recommended that, "Patients with stable viremia unable to fully suppress HIV replication should continue therapy and consideration should be given to the use of a PI-based regimen."

Royal Free and University College Medical School, London, UK; University Hospital, Zurich, Switzerland; Medizinische Poliklinik, Munich, Germany; Hospital Saint-Antoine, Paris, France; Medical University, Bialystok, Poland; Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, Netherlands; Copenhagen HIV Programme, Panum Institute, Copenhagen, Denmark; Copenhagen HIV Programme, Panum Institute and Centre for Viral Disease KMA, Rigshospitale, Copenhagen, Denmark.

12/9/08

Reference

AN Phillips, B Ledergerber, JR Bonger, and others. Rate of change in CD4 counts in patients with stable HIV viremia. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008.Journal of the International AIDS Society 11(Suppl 1): O17. November 10, 2008.

Adherence, Pharmacokinetics, and Metabolic Changes in Treatment-naive Patients Receiving Once-daily or Twice-daily Lopinavir/ritonavir (Kaletra): Study M05-730

Researchers have explored several strategies for making antiretroviral therapy more convenient and promoting improved adherence, including once-daily dosing. A series of posters at the 9th International Congress on Drug Therapy in HIV Infection (HIV9) this week in Glasgow, Scotland, presented data from studies of soft-gel capsule (SGC) and tablet formulations of the boosted protease inhibitor lopinavir/ritonavir (Kaletra) taken either once-daily (QD) or twice-daily (BID).

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