Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection

Abstract

Objectives To evaluate the effects of gender and initial antiretroviral regimen on decay of HIV RNA and virologic outcome. Methods We conducted a viral dynamics sub-study of A5142, a trial comparing lopinavir/ritonavir+efavirenz (LPV/EFV) versus LPV+2 NRTI (LPV) versus EFV+2 NRTI (EFV) in ARV-naive subjects. HIV RNA was measured at days 2, 10, and 14 in the sub-study and at weeks 1, 4, and 8 in A5142 participants. Two-phase viral decay was estimated in the sub-study with bi-exponential mixed-effects modeling and compared using Wilcoxon tests. Week 1 HIV RNA change was assessed as a predictor of virologic failure (HIV RNA above 50/200 copies/mL) at weeks 24–96 using logistic regression. Results 68 subjects were enrolled in the sub-study (median HIV RNA 4.9 log10 copies/mL). Median rates of phase-1 viral decay by treatment were 0.61(EFV/LPV), 0.53(LPV), and 0.63(EFV) day−1. Phase-1 decay was significantly faster for EFV than LPV (P=0.023); other comparisons were not significant (P>0.11). Viral decay did not differ by gender (P=0.10). Week 1 HIV RNA change, calculated in 571 participants of A5142, was greater for the EFV (median - 1.47 log10 copies/ml) than either the LPV/EFV or LPV groups (−1.21 and −1.16 log10 copies/ml, respectively; P<0.001). Week 1 HIV RNA change was associated with virologic failure above 50 copies/mL at weeks 24 and 48 (P≤0.018), but not above 200 copies/mL or at week 96. Conclusions Phase-1 decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV RNA change predicted virologic outcome to week 48, but not at week 96.

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

“…For instance, Haubrich et al [12] observed a greater viral decay in patients with pre-HAART viraemia >100,000 copies/ml than in those with pre-HAART viraemia <100,000 copies/ml after approximately 2 weeks of HAART. A potential explanation of this phenomenon is the presence of a larger infected cell population in patients with higher viraemia before starting treatment, predominantly done by longlived productively infected cells [12]. Whether this interesting result (with obvious therapeutic consequences) is driven by patients with very high viraemia (>500,000 copies/ml) or by all those with >100,000 copies/ml is not defined in that study.…”

“…The current definition of high viral load is >100,000 copies/ml, and nearly all studies, and guidelines, tend to adapt their analyses and statements to this threshold [2,6,12,[17][18][19][20][21]. For instance, Haubrich et al [12] observed a greater viral decay in patients with pre-HAART viraemia >100,000 copies/ml than in those with pre-HAART viraemia <100,000 copies/ml after approximately 2 weeks of HAART. A potential explanation of this phenomenon is the presence of a larger infected cell population in patients with higher viraemia before starting treatment, predominantly done by longlived productively infected cells [12].…”

“…These failures can be caused by several factors, such as drug potency, drug Introduction exposure, adherence, drug resistance, age and, above all, viral dynamics, pretreatment CD4 + T-cell count and viraemia level. Regarding viral dynamics, findings show that evaluation of changes in virus load 1-12 weeks after the start of treatment can serve as a prognostic indicator for longer term virological responses [10][11][12]. Currently, the measurement of viral load before starting and during HAART treatment is recommended by guidelines for the treatment of HIV-infected patients [5,6].…”

“…Indeed, plasma HIV RNA level has been considered for many years as a surrogate marker for treatment response and survival [2,[13][14][15][16]. In particular, patients starting HAART with HIV-1 viral load higher than 100,000 copies/ml and/or CD4 + T-cell count fewer than 200 cells/µl have a higher risk of clinical progression and lower virological response than those with lower HIV-1 viral load or higher CD4 + T-cell count [2,12,[17][18][19][20][21]. To minimize the risk of disease progression, these two thresholds are recommended by current guidelines to favour an early initiation of therapy [5,6].…”

Decay of Soluble CD30 and HIV-1 Plasma Viral Load during Early Highly Active Antiretroviral Therapy: A Short-Term Longitudinal Study

“…Since sCD30 decreases with decreasing HIV-1 pVL, it may be useful as an indicator for virological success during ART [8,10]. It is also known that early HIV-1 decay within one month of therapy can be predictive of long term outcomes [11][12][13]. However, it is unclear if sCD30 decline during the early stage of ART will be useful for predicting HIV-1 pVL suppression during this early phase of ART where immune reconstitution disease (IRD) and co-infections may be present [14].…”