Peter Gilbert

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..This assessment helps guide development of anti-HIV therapies that surmount the problem of drug resistance...

..In addition to uncovering a surprising immunological scenario, our results illustrate the utility of mechanistic modeling in biostatistics...

..The usability of PTE peptide set was manifested by detection of Nef-specific CTL responses in HIV-1 subtype B infections...

..These results demonstrate the risk of formula feeding to infants in sub-Saharan Africa, and the need for studies of alternative strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00197587...

..The simultaneous interval estimates are quite useful for identifying possible values of the contrast over time with a certain degree of confidence. The new proposals are illustrated with an example and a small simulation study...

..The asymptotic properties of the procedures are established. In addition, the methods are studied in simulations and are applied to HIV genetic sequence data collected in the first HIV vaccine efficacy trial...

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..A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection...

..g., readouts from laboratory assays) of vaccine-induced immune responses, and (2) by implementing the proposed semiparametric efficient method in trials where baseline predictors are available...

..Our objective is to help inform the decision-process for planning an initial efficacy trial design...

..Information on covariability should be better exploited in assessments of HIV-1 diversity and how to surmount it with vaccine design...

..The new method, which does not require a monotonicity assumption, is evaluated in a simulation study and is applied to data from the first HIV vaccine efficacy trial...

..The new method is evaluated in simulations and is applied to the vaccine trial data set...

..Third, we evaluate RV144 for completeness of end point ascertainment and integrity of blinding, necessary tasks for establishing robustly interpretable results...

..The methods are examined in simulations and are applied to two HIV examples. The methods for problem B address the general problem of comparing discrete frequency distributions between groups in a high-dimensional data setting...

..40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets...

..The assessment suggests that a vaccine demonstrating moderately durable effects to delay therapy and to ameliorate viremia merits consideration for licensure...

..We show how the procedures can be used for a sensitivity analysis that quantifies how the causal effect of vaccination varies with the presumed magnitude of selection bias...

..The new tests are evaluated theoretically and in a simulation study, and are applied to a dataset of 200 HIV sequences sampled from 21 children...

..Theoretical and empirical evidence are presented indicating the NPMLE and MIDMLE are inconsistent. Conversely, the CMLE is shown to be consistent in general and thus is preferred...

..Based on the principal stratification framework, we also address evaluation of potential immunological surrogate endpoints for infection...

..97; P=1.0) over all follow-up time. Conclusions: The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination...

..Although the data cannot definitively discriminate between these 2 explanations, (ii) appears to be more likely...

..We apply our methods to the world's first phase III HIV vaccine trial...

..The pre-ART viral load and CD4+ lymphocyte count trajectories were also comparable between the groups. Evidently, the vaccine did not affect HIV-1 disease progression...

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..We apply the method to the HIV vaccine trial data, showing that higher antibody levels are associated with a lower hazard of HIV infection...

..Other real and simulated examples are also discussed...

..Power generally increases with the maximum number of allowable challenges per animal, the per-exposure risk of infection in control animals, and the proportion of animals susceptible to infection...

..We conclude that inhibiting Nef could make a substantial reduction in disease burden, lengthening the time before the necessity of undertaking combination therapy with other antiretroviral drugs...

..The goal of these early trials is to narrow the number of candidate vaccines to the most promising candidates worthy of further study in efficacy trials...

..4, P =.1, and P =.7, respectively). Persons who acquire HIV-1 infection while enrolled in HIV-1 vaccine trials can be successfully followed after infection, to determine whether vaccines alter the course of HIV-1 infection...

..Based on these analyses, several approaches are proposed to enhance the breadth of vaccine responses and, hence, the potential protective efficacy...

..Correlated mutation analysis and structure mapping further refine the cross-neutralization determinants. The usability of this approach is confirmed by analysis of an Influenza H3N2 cross-reactive dataset...

..Here we assessed the magnitude and breadth of neutralizing antibody responses in Vax004...

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..Efforts to re-capture subjects at the end of study for failure assessment are helpful in some contexts, and may be considered in study planning...

..We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect...

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..This strategy avoids the potential for maternal nevirapine resistance...

..The adjustment is derived using a selection bias model based on the principal stratification framework of causal inference...

..When the main interest is in detecting early and/or late survival differences, these tests may be preferable to the other versatile and weighted log-rank tests that have been studied...

..However, such activity requires the presence of FcR-bearing effector cells. Our results provide further evidence that ADCVI may play a role in preventing HIV infection...

..Usage of other coreceptors was rare and apparently insignificant. These results enhance our understanding of HIV-1C biology, with implications for designing and testing therapeutic and prophylactic agents...

..87; 95% confidence interval, 0.58-1.29; P=0.49). The present study demonstrated that the expression of neither DCC nor p27Kip1 was predictive in poor survival outcome in patients with stage II or III colorectal cancer...

..By improving the design and analysis of efficacy and NHP trials for addressing these areas, the project will benefit public health. ..

..g., immune responses). The fourth aim is to develop accurate simultaneous confidence interval procedures for assessing time-varying effects of vaccination to prevent infection or post-infection outcomes. ..

..By improving the design and analysis of efficacy and NHP trials for addressing these areas, the project will benefit public health. ..