Abstract

Our long-term goals are to contribute to the fight against HIV/AIDS by developing useful statistical methods for the design, conduct, and analysis of research studies aimed at the prevention of HIV infection, the treatment of persons with HIV, and better understanding the inter-relationship between HIV, the immune system, and therapeutic interventions. During the period of the proposed research, we will focus on the following specific aims: 1. To develop statistical methods for prevention studies, with special emphasis on (1.1) estimating the timing of perinatal and vertical transmission of HIV based on diagnostic tests with imperfect specificity and time-dependent sensitivity, and (1.2)statistical methods for HIV preventive vaccine trials, especially in assessing vaccine efficacy and viral transmissibility in the presence of several viral subtypes; 2. To develop statistical methods for the analysis and design of structured interruption trials of host immune suppression, including: (2.1) estimation of the subdistribution of time to host immune suppression in the presence of incomplete follow-up of subjects in post-treatment evaluation phase, (2.2) methods for assessing the consequences of premature treatment interruption, including the time course of viral rebound, the probability of successful rechallenge, and in subjects who are successfully rechallenged, the distribution of time to host immune suppression, and (2.3) the design of structured interruption trials; 3. To develop statistical methods for analyzing HIV/AIDS data subject to interval and informatively missing observations, including (3.1) methods for assessing a primary response variable whose observation depends on the values of intermediate markers, (3.2) regression methods in the presence of interval-censored covariates, and (3.3) models for defining guidelines for the real-time monitoring of viral load for treatment failure, and methods for identifying factors that are associated with viral rebound; and 4. To develop methods for the analysis of Phase I studies, especially methods for designing and analyzing dose escalation studies for trials with bivariate outcome measures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI024643-15
Application #
6627976
Study Section
Special Emphasis Panel (ZRG1-SNEM-5 (01))
Program Officer
Gezmu, Misrak
Project Start
1987-04-01
Project End
2006-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
15
Fiscal Year
2003
Total Cost
$242,700
Indirect Cost

  Institution

Name
Harvard University
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Lok, Judith J; Yang, Shu; Sharkey, Brian et al. (2018) Estimation of the cumulative incidence function under multiple dependent and independent censoring mechanisms. Lifetime Data Anal 24:201-223
Lok, Judith J; Hughes, Michael D (2016) Evaluating predictors of competing risk outcomes when censoring depends on time-dependent covariates, with application to safety and efficacy of HIV treatment. Stat Med 35:2183-94
Prague, Melanie; Wang, Rui; Stephens, Alisa et al. (2016) Accounting for interactions and complex inter-subject dependency in estimating treatment effect in cluster-randomized trials with missing outcomes. Biometrics 72:1066-1077
Novitsky, Vlad; Wang, Rui; Rossenkhan, Raabya et al. (2013) Intra-host evolutionary rates in HIV-1C env and gag during primary infection. Infect Genet Evol 19:361-8
Tate, Janet P; Justice, Amy C; Hughes, Michael D et al. (2013) An internationally generalizable risk index for mortality after one year of antiretroviral therapy. AIDS 27:563-72
Wang, Rui; Ware, James H (2013) Detecting moderator effects using subgroup analyses. Prev Sci 14:111-20
Novitsky, Vladimir; Bussmann, Hermann; Logan, Andrew et al. (2013) Phylogenetic relatedness of circulating HIV-1C variants in Mochudi, Botswana. PLoS One 8:e80589
Gomez, Guadalupe; Lagakos, Stephen W (2013) Statistical considerations when using a composite endpoint for comparing treatment groups. Stat Med 32:719-38
Noubary, Farzad; Hughes, Michael D (2012) Factors affecting timing of antiretroviral treatment initiation based on monitoring CD4 counts. J Acquir Immune Defic Syndr 61:326-33
Claggett, B; Lagakos, S W; Wang, R (2012) Augmented cross-sectional studies with abbreviated follow-up for estimating HIV incidence. Biometrics 68:62-74

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