Effects of NRTI backbone on HIV RNA, CD4 counts and lipids for first-line boosted PI-based HAART: meta-analysis of 12 clinical trials in 4,896 patients
Journal of the International AIDS Society volume 11, Article number: P5 (2008)
Several ritonavir-boosted PIs (PI/r) are currently recommended for use in first-line therapies for HIV infection. TDF/FTC and ABC/3TC are widely used with these PI/r, but there is conflicting evidence on their relative efficacy: the ACTG 5202 and BICOMBO trials suggest higher efficacy for TDF/FTC, whereas the HEAT trial shows no efficacy difference between the NRTI backbones.
A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 4,896 antiretroviral naïve patients, where TDF/FTC (n = 3,340) or ABC/3TC (n = 1,556) was the NRTI backbone used with PI/r. For each NRTI backbone and PI/r, the percent HIV RNA <50 copies/mL at week 48 by standardised ITT TLOVR analysis were combined using inverse-variance weighting. The effect of baseline HIV-RNA, CD4 count and choice of NRTI backbone were examined using a weighted analysis of covariance. Changes in CD4 counts and lipids (TCHOL, TRIGS, HDL, LDL) were also assessed with the same methods.
Summary of results
For the TDF/FTC and ABC/3TC groups, there were no significant differences in median baseline CD4 (204 and 195, respectively) and mean log10 HIV-RNA (4.9 and 5.0, respectively). The efficacy of first-line HAART correlated with baseline HIV-RNA and CD4 count. Use of TDF/FTC was associated with higher rates of HIV-RNA suppression in each of the three third agents where data were available (LPV/r, fAPV/r and ATV/r). (Table 1.)
There was no difference in CD4 change to week 48 by type of PI or NRTI used. All lipid parameters showed significantly greater increases when ABC/3TC was used, vs. TDF/FTC. TCHOL and TRIGS showed significantly higher increases for LPV/r and fAPV/r, vs. ATV/r, SQV/r or DRV/r.
This systematic meta-analysis of standardised HIV-RNA <50 copy efficacy data at week 48, using the FDA TLOVR algorithm, suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone, relative to use of ABC/3TC. However, CD4 increases were similar across the range of NRTIs and PIs used. Lipid profiles also differed by choice of NRTI backbone or boosted PI.
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Hill, A., Sawyer, W. Effects of NRTI backbone on HIV RNA, CD4 counts and lipids for first-line boosted PI-based HAART: meta-analysis of 12 clinical trials in 4,896 patients. JIAS 11 (Suppl 1), P5 (2008). https://doi.org/10.1186/1758-2652-11-S1-P5
- Copy Efficacy
- Efficacy Difference
- NRTI Backbone
- Heat Trial
- Systematic MEDLINE