Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents

Abstract

Objective: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents.

Methods: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison.

Results: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (-0.63 versus -1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART.

Discussion: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.

Figure 1

Mean change in (A) log₁₀ plasma HIV RNA viral load and (B) CD4⁺ lymphocyte percentage point from baseline to 48 weeks in the total study cohort after starting a nucleoside reverse transcriptase inhibitor only antiretroviral regimen (NOAR) or highly active antiretroviral therapy(HAART). Error bars indicate standard deviations. The numbers of subjects with available observations at each time (N) are indicated at the bottom of both plots, with the NOAR group on top. LEGACY cohort, 2001-2006. (A) Note: P-values for weeks 24 and 48 are ≥ 0.05.

Figure 1

Mean change in (A) log₁₀ plasma HIV RNA viral load and (B) CD4⁺ lymphocyte percentage point from baseline to 48 weeks in the total study cohort after starting a nucleoside reverse transcriptase inhibitor only antiretroviral regimen (NOAR) or highly active antiretroviral therapy(HAART). Error bars indicate standard deviations. The numbers of subjects with available observations at each time (N) are indicated at the bottom of both plots, with the NOAR group on top. LEGACY cohort, 2001-2006. (A) Note: P-values for weeks 24 and 48 are ≥ 0.05.

Figure 2

Percentages of nucleoside reverse transcriptase inhibitor only antiretroviral regimen (NOAR)-treated and highly active antiretroviral therapy(HAART)-treated participants with adverse events reported at any time during the treatment period. LEGACY cohort, 2001-2006. Note: Only P-values < 0.05 are shown. P-values noted above represent comparisons between the NOAR and HAART columns for leukopenia(*) and anemia(†). P-values for other adverse events are ≥ 0.05.