Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice (original) (raw)
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Annals of Internal Medicine, 2001
Background: A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy. Design: Observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 ؋ 10 9 cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log 10 copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1-to 1.99-log 10 copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log 10 copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log 10 copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1-to 1.99-log 10 copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log 10 copies/mL decrease since baseline (P ؍ 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count > 0.10 ؋ 10 9 cells/L, 1.47 [95% CI, 1.00 to 2.16] compared with <0.050 ؋ 10 9 cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 ؋ 10 9 cells/L, 0.98 [CI, 0.61 to 1.57] compared with <0.050 ؋ 10 9 cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 ؋ 10 9 cells/L or greater (compared with <0.05 ؋ 10 9 cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [CI, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.
Aids Research and Human Retroviruses, 1999
Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55% ) experienced sustained suppression of HIV-1 RNA to , 500 copies/ml. Failure to reduce viral load to , 500 copies/ml within 6 months (initial failure) was observed in 51 patients (19% ). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hardgel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56% ) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was , 500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.
Virologic outcomes in early antiretroviral treatment: HPTN 052
HIV clinical trials, 2017
The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm(3) at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm(3) at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Overall, 93% of participants achieved viral suppression by 12 months. The annual inci...
AIDS Research and Human Retroviruses, 2015
Objective: Aim of this study was to evaluate the impact of HIV-1 very low level viremia (<50 copies/ml) on the 2-year risk of virological failure. Methods: A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/mL (outpatient clinic in Italy, first semester of 2010) was performed. HIV RNA was measured through real time Polymerase Chain Reaction (PCR) assay CAP/CTM HIV-1 version 2.0 (detection limit: 20 copies/mL) and stratified as undetectable RNA ("Target Not Detected", TND), <20 copies/mL, 20-50 copies/mL. After 96 weeks virological failure was defined as two consecutive viral loads above 50 copies/mL. Log-rank tests and a multivariate Cox proportional hazard model were used for uni-and multivariate analysis. Results: 1055 patients (71.4% male, 87.4% Caucasian, aged 46.7 years) were included: nadir and current CD4 cell count were 203 cells/mm 3 (106-292) and 554 cells/mm 3 (413-713.5). HIV RNA was undetectable in 781 patients (74%), <20 copies/mL in 190 patients (18%) and 20-50 copies/mL in 84 patients (8%). Virological failure was observed in 81 patients (7.7%); at multivariate analysis detectable RNA at baseline (p=0.017), HCV infection (p=0.020), more than 3 pills in the regimen (p=0.003) and duration of HIV RNA<50 copies/mL below 2 years (p<0.001) were independently associated with virological failure. In 14 patients newly selected resistance-associated mutations were observed. Conclusions: Undetectable HIV RNA by real-time PCR is significantly associated with a lower 2year risk of virological failure along with Ab HCV-negativity, longer viral control and lower pill burden. Studies investigating the management of residual viremia under antiretroviral treatment are warranted.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015
ACTG A5230 evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure on first-line regimens in Africa and Asia. Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200,000copies/mL. All subjects received LPV/r 400/100mg twice daily. Virologic failure (VF) was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200mg/tenofovir 300mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r-monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. 123 subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 /123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and...
2014
The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load <50 copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4 þ cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load (!500,000 vs. <100,000 HR 0.52; P < 0.001), a weighted genotypic susceptibility score (wGSS) <3 (HR 0.58; P ¼ 0.003), male sex (HR 0.76 P ¼ 0.001), and type of initial third drug employed (integrase inhibitor vs. boosted protease inhibitors HR 3.23; P < 0.001). In the subset with HIV-1 RNA Conflict of interest: ADB did not receive any financial support for his contribution to this study, but he has received prior research funding and/or consultancy honoraria from Abbott, Bristol-Myers Squibb, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Roche, and ViiV. SR has received research funding from Pfizer and have been involved in advisory boards or educational courses supported by the
PLOS One, 2006
Background. Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods. Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels ,500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results. Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event.