Risk factors for loss of virological suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression

Abstract

Background Risk factors for loss of virological response in patients receiving lopinavir/ritonavir (LPV/r) monotherapy as maintenance treatment have not been determined. Methods In 121 patients enrolled in the OK and OK04 clinical trials assigned to receive monotherapy with LPV/r, we attempted to identify factors associated with loss of virological suppression at 48 weeks, defined as confirmed serum HIV type-1 RNA>50 copies/ml, with missing data or changes caused by toxicity censored. Univariate and multivariate Cox proportional hazard models were used to calculate hazard ratios for the risk of loss of virological suppression. Results At week 48, 15 patients experienced loss of virological suppression. Probability of loss of virological suppression was 12.7%. Less than 9 months of maintenance of virological suppression prior to monotherapy, a lower baseline haemoglobin and low adherence measured by self-reported total missed doses in the week prior to study visit were associated with loss of virological suppression in the univariate analyses. Independent factors associated with loss of virological suppression by multivariate analyses were ≥2 visits with self-reported missed doses in the week prior to the study visit, a lower baseline haemoglobin and a nadir CD4+ T-cell count <100 cells/μl Conclusions Suboptimal adherence, lower baseline haemoglobin and a nadir CD4+ T-cell count <100 cells/μl were the main risk factors for losing virological suppression in patients randomized to monotherapy with LPV/r.

Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression

“…We did not find any association between virological failure and haemoglobin levels, adherence, atazanavir plasma concentrations or CD4 þ cell count nadir. It is possible that in our study, the importance of these variables in predicting the risk of virological failure was attenuated because of the uniformity of patient's characteristics (nadir CD4 þ cell count >100 cells/ml, similar type of antiretroviral regimen and similar treatment duration); on the contrary, we cannot exclude that our limited sample size may preclude our ability to assess the effects observed in the lopinavir/ritonavir monotherapy studies [37].…”

“…Hepatitis C coinfection was reported as a significant predictor of confirmed HIV-RNA elevations also in the MONET study both in the analysis at 48 weeks and at 144 weeks [14,34]. Other randomized clinical trials on protease inhibitor monotherapy did not evaluate the effect of this covariate [13,36,37]. We think it is unlikely that this result was seen simply by chance as the limited sample size (and the consequent low statistical power) of the monotherapy arm in the MODAt study could have obscured the effect of HCV on virological failure that was observed.…”

A Randomized Comparison of Second-Line Lopinavir/ Ritonavir Monotherapy versus Tenofovir/Lamivudine/ Lopinavir/Ritonavir in Patients Failing Nnrti Regimens: The HIV Star Study

“…The predictors of mono-LPV/r failure have been reported by other groups. In trials using mono-LPV/r as the maintenance therapy, lower baseline haemoglobin [28], CD4 + T-cell count [29] and adherence [28,29] were predictors of mono-LPV/r failure. However, these predictors could not be compared directly to our study because of the different scenarios of maintenance therapy in those studies versus salvage therapy in ours.…”

Meta-análisis sobre la eficacia de la estrategia de monoterapia con inhibidores de la proteasa potenciados en pacientes VIH+

“…Como comentamos anteriormente, dicho estudio se diferencia del resto por reclutar pacientes naive, con lo que sus resultados no pueden ser considerados equivalentes a los del resto de ensayos. Otros ana ´lisis de subgrupos de distintos trabajos muestran la adherencia al tratamiento como el principal predictor de respuesta virolo ´gica, seguido de niveles de CD4 nadir inferiores a 100 ce ´lulas/ml 22,23 . En nuestro estudio el ana ´lisis de las resistencias debidas a mutaciones frente a IP no ha sido posible debido a la variabilidad de los datos presentados en los estudios dependiendo de su metodologı ´a.…”