HIV-Infected Patients With Long-Term Viral Suppression Have Slower CD4 Recovery With Tenofovir Regimens: Presented at ACCP
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HIV-Infected Patients With Long-Term Viral Suppression Have Slower CD4 Recovery With Tenofovir Regimens: Presented at ACCP

By Crina Frincu-Mallos, PhD

PHILADELPHIA -- September 17, 2008 -- In HIV-infected patients with long-term viral suppression receiving treatment regimens containing tenofovir disoproxil fumarate, there is a trend towards lower gains in CD4 cells and opposite changes in CD3 and CD8 T cells, compared with patients not receiving tenofovir, researchers reported here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting.

Patients with HIV infection treated with combination antiretroviral therapy (cART) normally experience virological suppression and CD4 lymphocyte recovery.(1) However, CD4 lymphocyte recovery data indicate a high interpatient variability that could be dependent on the components of the cART regimen.(2)

Jens J. Kort, MD, PhD, Rand Schrader Clinic and Clinical Research Site Leader, Keck School of Medicine, University of Southern California, Los Angeles, California, presented the data in a poster session on September 14.

Dr. Kort and his colleagues analysed the lymphocyte subset recovery in HIV-infected patients, 99 receiving tenofovir and 81 receiving non-tenofovir-containing regimens. They also assessed whether the patient's ethnicity or the use of other antiretroviral drugs would have an impact on CD4 recovery. They analysed lymphocyte subsets CD3, CD4, and CD8 from both cohorts.

For the study, Dr. Kort and colleagues treated 136 men and 44 women with cART therapy over a period of 24 months, during which their plasma viral load was suppressed to <50 copies/mL. Patients were a mean of 43 years old (range, 34-55 years).

At nadir, CD4 counts were 244.5 +- 197.9 cells/mm3 in patients treated with tenofovir and 318.4 +- 238.9 cells/mm3 in the non-tenofovir-treated patients.

After 24 months, CD4 counts were 442.9 +- 252.2 cells/mm3 in tenofovir-treated patients and 578.1 +- 331.9 cells/mm3 in the non-tenofovir-treated patients.

The investigators used a stepwise linear regression model to study the association of CD4 T-cell subset change with tenofovir versus non-tenofovir therapy. The most profound difference occurred after 6 months of treatment, when the CD4 counts were significantly higher in the non-tenofovir group (P < .05).

Interestingly, when examining the percent change from baseline in CD3, CD4, and CD8, the researchers found no significant differences. These findings prompted them to suggest that the difference in absolute lymphocyte subsets was dependent on the baseline levels of lymphocytes, in particular CD4.

Comparing tenofovir- and non-tenofovir-containing regimens, there were differences among various ethnic groups. The analysis showed that African American patients had a lower CD4 recovery overall compared with Caucasians and Hispanics. The trend was not statistically significant, however, explained Dr. Kort.

For African American patients, CD4 counts went from 335.7 to 389.9 cells/mm3 in 12 months in the non-tenofovir-treated patients. For Caucasians, CD4 counts increased from 429.5 to 503.8 cells/mm3, while for Hispanics, CD4 counts went from 428.6 to 757.7 cells/mm3.

A similar trend was observed in patients treated with a tenofovir regimen during the same 12-month period. For African American patients, CD4 counts went from 511.5 to 631.9 cells/mm3, for Caucasians from 349.0 to 468.2 cells/mm3, and for Hispanics from 606.1 to 722.5 cells/mm3.

When Dr. Kort and colleagues looked at the impact of concomitant drugs on CD4 recovery, analysis of variance revealed a statistically significant difference in CD4 counts at 24 months in patients receiving tenofovir-containing regimens plus the non-nucleoside reverse transcriptase inhibitor efavirenz compared with patients on non-tenofovir-containing regimens plus efavirenz (P < .05).

These findings warrant further study in a larger cohort to assess the full implications for T-cell subset recovery, individualisation of cART, and genetic testing, concluded Dr. Kort.

1. Mocroft A et al. AIDS. 2006;20:1141-1150.
2. Kakuda TN et al. AIDS. 2004;18:2442-2444.

[Presentation title: Effect of Tenofovir-Containing Antiretroviral Therapy on T Lymphocyte Changes in an Ethnically Diverse Population With Fully Suppressed HIV in Plasma. Abstract 6]

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