Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline

Abstract

Objective-Compare the initial phases of virologic decay when acute/early and advanced HIVinfected adults are administered the same treatment regimen.Design-Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression.Methods-We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIVspecific immune responses at baseline, and the presence of drug resistance-conferring mutations.Results-There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence.Conclusions-Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum. [6]. The natural history of untreated infection then involves years of clinical stability, followed by inexorable CD4+ Tcell count decline (reviewed in [7]). In the advanced immunosuppression setting, antiretroviral therapy (ART) results in rapid plasma viremia decline, CD4+ T-cell count improvement, and decreased disease progression and mortality [8]. Treatment during acute seroconversion also hastens the viremia decline beyond the natural equilibration seen in untreated patients [9,10], but there is no consensus regarding the long-term risks and benefits of early treatment [7,8,11].Very limited data directly compare treatment responses among individuals with early and late stage disease. It remains unclear whether comparably high viremia levels observed at the opposite ends of the disease spectrum would decline at the same rate in response to identical treatment interventions. Previously, we completed a pathogenesis-driven study involving both acute/early and highly advanced HIV-infected patients [12]. We revisited this unique dataset to compare and contrast treatment responses at the disease spectrum extremes. We hypothesized that virologic suppression would be more rapid and complete during acute than advanced disease, perhaps because of rescue of immune clearance mechanisms [13] or incomplete population of viral reservoirs [14]. MethodsAll studies were approved by the Institutional Review Board. Eligibility required no prior ART, Karnofsky performance of at least 80, and safety laboratory results were within acceptable rang...

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