They might be very suitable for designing specific inhibitors

Since only 5% of all patients starting HAART in the Malawi report were categorized as lost to followup, however, the effects of TWS119 GSK-3 inhibitor deaths among those initially considered lost on overall survival estimates would likely have been less pronounced than was shown in this study, where the initial loss to follow-up rate was approximately 17%. This study extends findings from the Malawi study by documenting the effect of undetected deaths on overall survival estimates, and suggests that the magnitude of this effect likely relates both to the overall loss to follow-up rate and the proportion of deaths among these individuals. Since losses to follow-up in several large public antiretroviral therapy clinics in Zambia, South Africa, Cote d��Ivoire, additional settings in Malawi, Uganda, Kenya and in the Antiretroviral Therapy in Lower Income Vorinostat countries collaboration have been substantial, underestimation of deaths after HAART initiation in many reports from the region could be common. The finding of substantial death rates among patients who are lost to follow-up also suggests that death rates after HAART initiation in the developing world may be higher than previously suspected. The ART-LINC study comparing outcomes after antiretroviral therapy initiation in low and high income countries excluded clinics that did not trace patients from survival analyses, found greater ascertainment of deaths in developed countries, and documented higher rates of losses to follow-up in developing countries. Thus, while inability to ascertain outcomes among patients lost to follow-up could bias mortality estimates in both the ART-LINC and the ART-CC data, higher rates of losses to follow-up in the ART-LINC patients creates the possibility that deaths may have been underestimated to a greater degree in this group. This study differs from several previous reports in that we performed prospective data collection on patients consecutively initiating HAART at a large antiretroviral therapy program in sub-Saharan Africa specifically to determine definitive outcomes on patients who were initially considered lost to follow-up and to compare survival estimates and risk factors for death before and after active tracing was performed. Although the ART-LINC collaboration documented higher rates of loss to follow-up among clinics which did not trace patients, this analysis compared one type of clinic to another rather than comparing outcomes before and after tracing within a single group of patients. Furthermore, while the study from Malawi confirmed a high rate of death among patients who were lost, the effect of these deaths on estimates of overall outcomes was not evaluated. Another difference of this study from the Malawi study is that we analyzed the effects of losses to follow-up on reported risk factors for death after HAART initiation.

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