HIV Transmission Statistical Modelling
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This book is dedicated to all
HIV-infected children.
Preface
HIV is a scourge. Research of almost 35 years into human immunodeficiency virus
(HIV) has conceivably precipitated more questions than answers. It is widely
understood that unprotected sexual intercourse, intrauterine device (IUD), and
mother to child transmission (MTCT) are the main modes of HIV transmission.
It’s been more than three decades at global level it is an addressable issue, that has
played a significant role of HIV prevention program at national and global level. Due
to the paucity of enquiry-based study, the policy makers were unable to implement
new scientific and innovative eradicated programs of HIV MTCT. In this propin-
quity of the research gap, the HIV model-based study will help to elucidate observed
patterns of HIV vertical transmission rate at global scenario. However, the modelling
techniques are routinely used to estimate national and global trends of the number of
infants infected through HIV- MTCT. Such type of fitted models depend on the input
data sets from individual antiretroviral therapy (ART) centers. The present study
intervention has demonstrated different statistical and mathematical models based on
the primary and secondary HIV life data sets collected from thrust area (high
prevalence state). The collected HIV massive data sets were demonstrated with
various mathematical and statistical models. These fitted models produce an insight
analytical algorithms to prove HIV transmission rate at greater accuracy and easily
substitute HIV transmission with prior and posterior probabilities (both peripartum
and postnatal) for estimation of maximum likelihood (MLE’s) of HIV transmission
rate and algebraic bifurcations (forward/backward). Intervention of maternal
infections (either incident or prevention), timing of infection, comorbidity, and
clinical history have been utilized for the determination of HIV transmission rate
(based on HIV MTCT infection rate). Since the fitted mathematical and statistical
models would clarify the full implications of the research findings and global
population dynamism of the vertical transmission (MTCT), building of this few
cited mathematical models has been used extensively over the past decades to
examine the epidemic of HIV and acquired immunodeficiency syndrome (AIDS) at
global level. As per the normative results of the HIV vertical transmission,
these fitted models will serve as an important analytical algorithms to recognize
the inherent limitations of massive HIV data sets; impart scientific evidence for
researchers, clinicians, and public health administrators etc. In this present book, a
several important practical and statistical implications and deep illustrations are
discussed, which seem to be simple yet complex, that need to be addressed and
vii
viii Preface
examined while analyzing HIV MTCT massive data sets. For example, HIV itself is
a life-threatening deadly disease. However, too many questions arose from HIV life
data sets, and the researchers/statisticians/clinicians are facing several pitfalls for the
simulation and reduction of HIV massive data sets while carrying tricky situations of
hypothesis testing and decision-making problems at larger population level. Major-
ity of the chapters tailored in this book, which can attempt to demonstrate various
techniques of building mathematical and statistical models while analyzing HIV
transmission from mother to child in HIV real-life data sets. The present book
consists of 13 chapters. Chapter 1 describes introduction of HIV transmission,
brief review of the published and unpublished literature from 1997 to 2019, building
of mathematical and statistical modelling techniques of HIV MTCT, objectives and
chapterization of the book, real-life data sets, methodology, variables considered for
the study, HIV serological markers, different patterns of HIV, TB co-infection
among children living with HIV (CLHIVs), etc. Chapter 2 discusses the statistical
modelling of HIV transmission. Chapter 3 describes the HIV vertical transmission
DTSM simulation models from global and national perspectives and the validity of
the model which was simulated by different varied parameters. Chapter 4 describes
large data matrices, random walk model, and application of entropy in HIV mother
to child transmission. This theoretical issue was formulated with suitable
illustrations and various examples by using real-life HIV MTCT data sets and also
fitted models that describe the different techniques of data reduction driven by the
random walk free probability values. Chapter 5 deals with statistical modelling on
postnatal transmission of HIV type I infection from mother to child on global
perspectives and examines the applicability of different statistical models in real-
life data sets of HIV mother to child transmission and antenatal care (ANCs) women.
Chapter 6 gives survivability and growth model approach to CD4 counts of people
living with HIV (PLHIVs). This chapter also describes briefly and discusses the
various issues of growth models and its applications towards estimation of survival
rate in real-life data sets. Chapter 7 discusses predictive model approach to HIV TB
co-infection in vertical transmission. Chapter 8 gives fitted Bayesian modelling
approach to HIV transmission and describes Gaussian emulator approach that was
used to extract the probability values of HIV transmission, models that were
formulated by networking niche, and also describe frequentist and Bayesian model
differences. Chapter 9 discusses HIV projection models, while Chap. 10 discusses
the simulation modelling techniques of HIV/AIDS. Chapter 11 describes the genetic
variants of HIV mother to child transmission and its meta-analysis, which was done
for the real historical data sets, and have also extracted HIV subtype B and C env
genes from 190 mother-infant pairs at global level. Chapter 12 deals with the
statistical perspective approach to selection of sample. Chapter 13 describes the
main significance of the entire book for induction of mathematical and statistical
models to prove new formulated models of HIV mother to child transmission at
population level. The prominence of the entire intact of the book traces salient
objectives and practical applicability to learn what methods are available and most
importantly when they should be applied in real life. Many illustrations accord to
Preface ix
clarify the use of mathematical models and to substantiate what conclusions can be
made at the right time. All the topics are driven purely on the HIV transmission
research gaps and its mechanisms, according to the level of apprehension of the
research scholars, policy makers, clinicians, and public health administrators.
Bangaluru, Karnataka, India D. M. Basavarajaiah
Chennai, Tamil Nadu, India Bhamidipati Narasimha Murthy
Acknowledgments
First and foremost, praises and thanks to the God, the Almighty, for his showers of
blessings throughout our research work to complete the research successfully. We
are grateful to all of those with whom we have had the pleasure to work with during
this and other related HIV research works. This book is tailor based on research work
conducted on children living with HIV (CLHIV) and ANCs between 2009 till date.
We are grateful to a number of friends and colleagues who have encouraged us to
start the research work, to preserve it, and finally to publish it. We would like to
specially thank Prof. Rajashekaraiah, Vijaya PU College, for his technical supports
for proof reading and all the officers of the National AIDS Control Organization,
Government of India, for sharing very good HIV data for this research work. Finally,
we would like to acknowledge with gratitude the support and love of our family –our
parents who kept us going. This book would not have been possible without them.
We feel immensely very proud for extending our heartiest thanks to the HIV-infected
children who participated during this study period.
xi
Contents
1 Introduction of HIV Transmission . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 WHO Transmission Through BF Makes the Following
Recommendation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.3 CD4 Cell Count Approach to HIV Transmission . . . . . . . . . . . 9
1.4 RNA Plasma Viral Load Approach to HIV Transmission . . . . . 10
1.5 Periodic Variation of ANC CD4 Counts . . . . . . . . . . . . . . . . . 10
1.6 CD4 Percentage of ANCs (μ/dL) . . . . . . . . . . . . . . . . . . . . . . 11
1.7 ANC Viral Load and Sexual Transmission (Copies per mL) . . . 11
1.8 Salient Features of HIV MTCT Prevention Strategies Practiced at
Global Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.9 Routine HIV Testing During Pregnancy . . . . . . . . . . . . . . . . . 14
1.10 Detecting of HIV Infection Using Blood Tests . . . . . . . . . . . . 14
1.11 Opt-In and Opt-Out Approach . . . . . . . . . . . . . . . . . . . . . . . . 14
1.12 Counseling Woman Who Refuses HIV Testing . . . . . . . . . . . . 15
1.13 Discussing HIV Test Posttest Counseling . . . . . . . . . . . . . . . . 16
1.14 Posttest Counseling for HIV Pregnant Women . . . . . . . . . . . . 16
1.15 Posttest Counseling for HIV-Negative Women . . . . . . . . . . . . 16
1.16 Additional Care for the HIV-Positive Woman During Pregnancy . . 17
1.17 Topical Antiseptic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.18 Caesarean Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.19 Immunoglobulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.20 Avoidance of Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.21 Vitamin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.22 Global and National Epidemiological Trend . . . . . . . . . . . . . . 19
1.23 Global Trend . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.24 Economic and Demographic Impact at National Level . . . . . . . 21
1.25 Statistical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.26 Review of Literature Survey . . . . . . . . . . . . . . . . . . . . . . . . . 23
1.27 Objectives of the Book . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
1.28 Organization of Book . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.29 Description of Study Area . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
1.29.1 Subgroup Analysis Study Site . . . . . . . . . . . . . . . . . 36
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1.30 Methods of Model Formulation: Source of Secondary HIV Data
Set . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
1.30.1 Inclusion Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . 38
1.30.2 Exclusion Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . 38
1.31 CD4 Cell Count (Micro/dL) . . . . . . . . . . . . . . . . . . . . . . . . . . 38
1.31.1 RNA Plasma Viral Load (Micro/dl) . . . . . . . . . . . . . 38
1.31.2 Highly Active Antiviral Therapy (HAART) . . . . . . . 39
1.31.3 WHO Clinical Stages . . . . . . . . . . . . . . . . . . . . . . . 39
1.32 HIV-Opportunistic Infections (OIs) . . . . . . . . . . . . . . . . . . . . 40
1.32.1 Candidiasis of Bronchi, Trachea, Esophagus, or Lungs . . 40
1.32.2 Oral Thrush . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
1.32.3 Invasive Cervical Cancer . . . . . . . . . . . . . . . . . . . . . 43
1.32.4 Coccidioidomycosis . . . . . . . . . . . . . . . . . . . . . . . . 43
1.32.5 Progressive Forms . . . . . . . . . . . . . . . . . . . . . . . . . 44
1.32.6 Disseminated Coccidioidomycosis . . . . . . . . . . . . . . 44
1.32.7 Cryptococcosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
1.32.8 Cytomegalovirus (CMV) . . . . . . . . . . . . . . . . . . . . . 45
1.32.9 HIV Encephalopathy . . . . . . . . . . . . . . . . . . . . . . . . 45
1.32.10 Herpes Simplex . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
1.32.11 Histoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
1.32.12 Isosporiasis, Chronic Intestinal (Greater Than 1
Month’s Duration) . . . . . . . . . . . . . . . . . . . . . . . . . 47
1.32.13 Kaposi Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
1.32.14 Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
1.32.15 Mycobacterium avium Complex (MAC) . . . . . . . . . . 49
1.32.16 Tuberculosis (TB) . . . . . . . . . . . . . . . . . . . . . . . . . . 49
1.32.17 Pneumocystis carinii Pneumonia (PCP) . . . . . . . . . . 50
1.32.18 Pneumonia (Recurrent) . . . . . . . . . . . . . . . . . . . . . . 50
1.32.19 Progressive Multifocal Leukoencephalopathy . . . . . . 51
1.32.20 Salmonella Septicemia (Recurrent) . . . . . . . . . . . . . 51
1.32.21 Toxoplasmosis of Brain . . . . . . . . . . . . . . . . . . . . . 51
1.32.22 AIDS (Acquired Immunodeficiency Syndrome) . . . . 52
1.32.23 Modes of Delivery: Infected Pregnant Women . . . . . 52
1.32.24 Mechanisms and Risk Factors of HIV Transmission . . . 52
1.32.25 Late Pregnancy and Intrapartum Transmission . . . . . 53
1.32.26 Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
1.33 Timing of HIV MTCT to Infant Non-BF Population . . . . . . . . 53
1.33.1 Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
1.33.2 Rates of Transmission . . . . . . . . . . . . . . . . . . . . . . . 54
1.34 Confidentiality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2 Statistical Modeling of HIV Transmission . . . . . . . . . . . . . . . . . . . . 59
2.1 History of Modelling of HIV Transmission . . . . . . . . . . . . . . . 59
2.2 Deterministic Theory of HIV Epidemics . . . . . . . . . . . . . . . . . 59
Contents xv
2.3 Rationality of the Good Model . . . . . . . . . . . . . . . . . . . . . . . . 60
2.4 HIV Heterosexuality (TM1) . . . . . . . . . . . . . . . . . . . . . . . . . . 60
2.5 HIV Models for Heterosexual Transmission . . . . . . . . . . . . . . 61
2.5.1 Probability of Infection . . . . . . . . . . . . . . . . . . . . . . 61
2.6 Knowledge of Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.7 Global Illustration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.8 CASCADE Linkage Model . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.9 The Proposed Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
2.9.1 The Assumptions of the Model Are as Follows . . . . . 64
2.9.2 Structure and Notations . . . . . . . . . . . . . . . . . . . . . . 64
2.10 Computation of Infection Rate . . . . . . . . . . . . . . . . . . . . . . . . 67
2.11 Assessment of the Parameters . . . . . . . . . . . . . . . . . . . . . . . . 68
2.12 Model Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2.13 Infected Needles (TM2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2.14 HIV Spread Through Clinical Injections . . . . . . . . . . . . . . . . . 71
2.14.1 Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
2.14.2 Drug Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
2.14.3 Sample Proportion Method . . . . . . . . . . . . . . . . . . . 73
2.15 Blood Transfusion (TM3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
2.15.1 The Model Fitting . . . . . . . . . . . . . . . . . . . . . . . . . . 75
2.15.2 Role of Blood Units . . . . . . . . . . . . . . . . . . . . . . . . 75
2.15.3 Joint Effect of γ and ά . . . . . . . . . . . . . . . . . . . . . . 77
2.15.4 Cumulative Incidence . . . . . . . . . . . . . . . . . . . . . . . 78
2.15.5 Standard Error (S.E) of m (t) . . . . . . . . . . . . . . . . . . 78
2.15.6 Estimation of Parameters . . . . . . . . . . . . . . . . . . . . . 79
2.15.7 Practical Illustrations in Indian Context . . . . . . . . . . 79
2.16 Perinatal Transmission (TM4) . . . . . . . . . . . . . . . . . . . . . . . . 80
2.16.1 The Model Formation . . . . . . . . . . . . . . . . . . . . . . . 80
2.16.2 Estimation Techniques . . . . . . . . . . . . . . . . . . . . . . 80
2.16.3 Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
2.17 National/Global Policy Implications of Modelling . . . . . . . . . . 82
2.18 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
3 HIV Vertical Transmission DTSM Simulation Models: Global and
National Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.2 Model Formulation of Disease Transmission and Susceptible
Model (DTSM–Model) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.3 Description of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.3.1 Model Implications . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.4 Positivity of Solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
3.5 Stability Analysis of the Model . . . . . . . . . . . . . . . . . . . . . . . 95
3.6 Equilibrium Points of the Model . . . . . . . . . . . . . . . . . . . . . . 95
3.7 Computation of the Basic Reproduction Number (R0) . . . . . . . 96
xvi Contents
3.8 The Endemic Equilibrium and Local Stability . . . . . . . . . . . . . 97
3.9 Model Forward Bifurcation . . . . . . . . . . . . . . . . . . . . . . . . . . 98
3.10 Determination of Bifurcation Parameters (a and b) . . . . . . . . . . 101
3.11 Global Stability of the Endemic Equilibrium . . . . . . . . . . . . . . 102
3.12 The Numerical Simulations of the Model . . . . . . . . . . . . . . . . 105
3.13 Numerical Simulations of the Model . . . . . . . . . . . . . . . . . . . . 122
3.14 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
4 Large Data Matrices: Random Walk Model and Application of
Entropy in HIV Mother to Child Transmission (MTCT) . . . . . . . . . 127
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
4.2 Model Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4.2.1 Theorem (1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4.2.2 Theorem (2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
4.3 HIV Random Walk on Disease-Free Groups and Free Probability
Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
4.4 Entropy in HIV Model Formulation . . . . . . . . . . . . . . . . . . . . 130
4.5 Model Proof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
4.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
5 Statistical Models of Postnatal Transmission of HIV Type-I Infection
from Mother to Child on Global Perspectives . . . . . . . . . . . . . . . . . 135
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
5.2 Model Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
5.3 Intrauterine and Intrapartum Transmission . . . . . . . . . . . . . . . 137
5.4 Transmission Probability at or Before Birth, in the Absence of
ARV Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.5 Model Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
5.6 Model Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
5.7 HIV Vertical Transmission Statistical Model-Model Description 142
5.8 Formulation of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
5.9 Poisson Distribution Model . . . . . . . . . . . . . . . . . . . . . . . . . . 143
5.10 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
5.11 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
5.12 Genetic Model Approach to Plasma RNA Viral Load (VL) and
CD4 Count for MTCT Transmission . . . . . . . . . . . . . . . . . . . 153
5.13 Model Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
5.14 Formulation of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
5.15 Assumption of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
5.16 Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
5.17 Genetic Correlation (1 r2 1) . . . . . . . . . . . . . . . . . . . . . 155
5.18 Estimation of Heritability (0 h2 1) . . . . . . . . . . . . . . . . . . 156
5.19 Numerical Results of Genetic Models . . . . . . . . . . . . . . . . . . . 156
Contents xvii
5.20 Genetic Model Results and Discussion . . . . . . . . . . . . . . . . . . 160
5.21 Robustness of Genetic Model . . . . . . . . . . . . . . . . . . . . . . . . . 161
5.22 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
5.23 Modelling on RNA Plasma Viral Load and CD4 Count
(Micro/dL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
5.23.1 Linear Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
5.23.2 Exponential Model . . . . . . . . . . . . . . . . . . . . . . . . . 162
5.23.3 Logarithmic Model . . . . . . . . . . . . . . . . . . . . . . . . . 162
5.23.4 Power Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
5.24 Simulated Numerical Results . . . . . . . . . . . . . . . . . . . . . . . . . 162
5.25 Results and Discussion of the Model . . . . . . . . . . . . . . . . . . . 165
5.26 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
6 Survivability and Growth Model Approach to CD4 Counts of
PLHIVs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
6.2 Model Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
6.3 Survival Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
6.4 Concept of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
6.5 Compound Growth Rate Model (CGR) . . . . . . . . . . . . . . . . . . 173
6.6 Model Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
6.7 Model Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
6.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
7 Predictive Model Approach to HIV TB Co-infection in Vertical
Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
7.2 Methods and Data Source . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
7.3 Formulation of Model (Logistic Regression Model) . . . . . . . . . 182
7.4 Model Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
7.5 Model Proof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
7.6 HIV TB Co-infection Children Manifested Dermatological
Complications at Low CD4 Count (CD4 Count <25% Micro/dl) . . 190
7.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
8 Bayesian Artificial Neural Network (ANN) Model Approach to AIDS
Associated Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.2 Probabilistic Diagnostic Gaussian Model for Risk Analysis . . . 195
8.3 Practical Component of DALY (Stroke) . . . . . . . . . . . . . . . . . 199
8.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
8.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
xviii Contents
9 HIV Projection Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
9.2 Model Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
9.3 Baseline Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
9.4 Logistic Regression Model . . . . . . . . . . . . . . . . . . . . . . . . . . 212
9.5 Curve Fitting Estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
9.6 Logit Model Reflects the 2 2 Contingency Table . . . . . . . . . 213
9.7 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
9.8 Estimation Models on CD4 Count and Plasma RNA Viral Load . . 217
9.9 Double Hit (Event) Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
9.10 Compound Growth Rate (CGR) Model . . . . . . . . . . . . . . . . . . 218
9.11 Exponential Smoothing Model . . . . . . . . . . . . . . . . . . . . . . . . 219
9.12 Moving Average Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
9.13 Study Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
9.13.1 Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
9.13.2 Measurements and Evaluations . . . . . . . . . . . . . . . . 220
9.13.3 Patient Population and Baseline Characteristics . . . . . 221
9.13.4 Baseline Plasma Viral Load and Immunological
Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
9.14 Model Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
9.15 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
10 Simulation Modelling Techniques of HIV/AIDS . . . . . . . . . . . . . . . 227
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
10.2 Rationality of the Stochastic Modelling . . . . . . . . . . . . . . . . . 227
10.3 Distribution of Time to Onset . . . . . . . . . . . . . . . . . . . . . . . . . 228
10.4 Basic Concepts of Immune Failure . . . . . . . . . . . . . . . . . . . . . 229
10.5 Uncertainties in Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
10.6 Need for Precise Time to Onset . . . . . . . . . . . . . . . . . . . . . . . 231
10.7 A Staged Markov Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
10.8 Double Hit Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
10.9 Independent X1 and X2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
10.10 Illustration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
10.11 Dependent X1 and X2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
10.12 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
10.13 Model for Probability of Infection . . . . . . . . . . . . . . . . . . . . . 236
10.14 Choice for the Distributions of N and C . . . . . . . . . . . . . . . . . 236
10.15 Estimation of Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
10.16 Modelling of HIV Transmission . . . . . . . . . . . . . . . . . . . . . . . 237
10.17 Case (A): Perfect Mixing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
10.18 Case B: Imperfect Mixing . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
10.18.1 Duration of the Epidemic . . . . . . . . . . . . . . . . . . . . 240
Case C: Spreaders Active for a Random Time . . . . . . . . . . . . . . . . . . . 240
10.19 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Contents xix
10.20 HIV Disease Progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
10.21 The Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
10.21.1 Probability distribution model and parameters
estimation of HIV DATA . . . . . . . . . . . . . . . . . . . . 243
10.22 Applicability of Probability Models . . . . . . . . . . . . . . . . . . . . 244
10.23 Application of Statistical Inference . . . . . . . . . . . . . . . . . . . . . 244
10.24 AIDS Projection by Using Large Massive Data Sets . . . . . . . . 245
10.24.1 Accuracy of Projection . . . . . . . . . . . . . . . . . . . . . . 245
10.24.2 Applicability of Classical Methods . . . . . . . . . . . . . . 245
10.24.3 Extrapolation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
10.24.4 Time Series Analysis . . . . . . . . . . . . . . . . . . . . . . . 245
10.25 Model Regression Method . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
10.26 Traditional Methods for AIDS Projection . . . . . . . . . . . . . . . . 246
10.27 Methods of Counts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
10.28 Smoothing of Exponential Trend . . . . . . . . . . . . . . . . . . . . . . 247
10.29 Minimizing Forecast Error . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
10.30 Convolution Equation at Population Level . . . . . . . . . . . . . . . 248
10.31 Advanced Modelling Techniques with Respect to
Non-parametric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
10.32 Regression Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
10.33 Assessment of MSE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
10.34 Stage-Specific Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
10.35 Age-Specific Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
10.36 Cause-Wise Projection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
10.37 Possible Overlapping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
10.38 Estimation of Survival Function . . . . . . . . . . . . . . . . . . . . . . . 254
10.38.1 Factors Affecting HIV Data Sets . . . . . . . . . . . . . . . 254
10.38.2 Effect of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . 254
10.38.3 AIDS Algorithmic Model . . . . . . . . . . . . . . . . . . . . 254
10.38.4 Uncertainties in Back Calculation . . . . . . . . . . . . . . 255
10.39 Window Period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
10.40 Over-projection of AIDS Counts . . . . . . . . . . . . . . . . . . . . . . 256
10.41 Choice of Infection Density . . . . . . . . . . . . . . . . . . . . . . . . . . 256
10.42 Back Calculation Methods for Global HIV Data Set . . . . . . . . 256
10.43 Alternative Method to Evaluate HIV Infections . . . . . . . . . . . . 257
10.44 Seropositivity Rate as Key Parameter . . . . . . . . . . . . . . . . . . . 257
10.45 Projection Formula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
10.45.1 Stratification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
10.46 State-Wise Projections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
10.47 Validation of Projected r(t) . . . . . . . . . . . . . . . . . . . . . . . . . . 259
10.48 Illustration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
10.49 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
10.50 Data Versus Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
10.51 AIDS Data Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
10.52 Decision-Making on DBM . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
10.53 AIDS Data Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
xx Contents
10.54 HIV/AIDS Surveillance in India . . . . . . . . . . . . . . . . . . . . . . . 264
10.55 HIV Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
10.56 AIDS Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
10.57 Need for AIDS Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
10.58 Model for HIV/AIDS Database in India . . . . . . . . . . . . . . . . . 266
10.59 Database Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
10.60 Data Security . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
10.61 Agreement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
10.62 AIDS Control Center (ACC) and Its Objectives . . . . . . . . . . . . 268
10.63 Flow of Data into the Database . . . . . . . . . . . . . . . . . . . . . . . 268
10.64 AIDS Data Flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
10.64.1 Record . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
10.64.2 Database Structure . . . . . . . . . . . . . . . . . . . . . . . . . 269
10.64.3 Database Questionnaire . . . . . . . . . . . . . . . . . . . . . . 269
10.65 Information on Code Assignment . . . . . . . . . . . . . . . . . . . . . . 270
10.66 Empirical Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
10.67 Compilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
10.67.1 Correlation and Regression . . . . . . . . . . . . . . . . . . . 273
10.67.2 HIV Infections in India . . . . . . . . . . . . . . . . . . . . . . 273
10.68 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
11 Meta Analysis of Genetic Variants of HIV Mother to Child
Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
11.2 Variation of Host and Viral Genetics in HIV . . . . . . . . . . . . . . 281
11.3 Selected Host Factors Influencing MTCT of HIV Type I . . . . . 282
11.3.1 Genetic Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
11.3.2 Chorioamnionitis (Infection of the Fetal
Membranes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
11.3.3 Sexual Transmitted Infections . . . . . . . . . . . . . . . . . 284
11.3.4 Malaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
11.3.5 Tuberculosis (TB) . . . . . . . . . . . . . . . . . . . . . . . . . . 285
11.3.6 Behavioral Factors . . . . . . . . . . . . . . . . . . . . . . . . . 285
11.3.7 Maternal Nutritional Status . . . . . . . . . . . . . . . . . . . 286
11.4 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
11.5 Effect of Viral Genotype for MTCT . . . . . . . . . . . . . . . . . . . . 289
11.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
11.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
12 Statistical Perspective Approach to Selection of Sample . . . . . . . . . 295
12.1 Statistical Dealing with Success of Good Research . . . . . . . . . 295
12.2 Research Perspectives in New Horizon . . . . . . . . . . . . . . . . . . 296
12.3 Statistical Thinking on Thematic Research Area . . . . . . . . . . . 298
12.4 Formulation and Frame Work of Research Project . . . . . . . . . . 298
Contents xxi
12.5 Sample Size Determination . . . . . . . . . . . . . . . . . . . . . . . . . . 299
12.6 The Level of Precision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
12.7 The Confidence Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
12.7.1 Using a Sample Size of a Similar Study . . . . . . . . . . 301
12.7.2 Degree of Variability . . . . . . . . . . . . . . . . . . . . . . . 301
12.7.3 Using Published Tables . . . . . . . . . . . . . . . . . . . . . . 301
12.7.4 Using a Census for Small Populations . . . . . . . . . . . 303
12.8 Merits of Sample Size Determination . . . . . . . . . . . . . . . . . . . 303
12.9 Demerits of Sample Size Determination . . . . . . . . . . . . . . . . . 303
12.10 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
12.11 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
12.12 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
13 Summary and Implications for Future Study . . . . . . . . . . . . . . . . . 309
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
13.2 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
13.3 HIV MTCT Data Sets and Methodology . . . . . . . . . . . . . . . . . 311
13.4 Salient Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312
13.5 Significance of the Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
13.6 Study Limitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
13.7 Implication for Future Research . . . . . . . . . . . . . . . . . . . . . . . 313
13.8 Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
About the Authors
D. M. Basavarajaiah is an Associate Professor and Head of the Department of
Statistics and Computer Science, Karnataka Veterinary Animal and Fisheries
Sciences University (B), Hebbal, Bangalore. He holds a Ph.D from the National
Institute of Epidemiology (NIE), ICMR, Chennai, affiliated to the University of
Madras. His research focuses on statistical theory, statistical modelling on high
dimensional datasets of agriculture, medicine, veterinary and animal sciences. He
has written sixty-eight research articles and four academic books, and is serving as
an editorial board member and scientific board advisor for various international
journals. He is a life member of numerous academic organizations, and has received
several accolades for his academic and research excellence, such as the “Chartered
Scientist Award from the Science Council, United Kingdom in collaboration with
the Royal Statistical Society; Best Reviewer award 2016 from TRANS STELLAR’
Journal Publications and Research Consultancy ,TJPRC Ltd., (NAAS rated
Journals); Fellow of the Royal Statistical Society, UK, Fellow of the Mathematical
Society, UK , Bharathshikshratana and Indo-Dubai Achiever’s Pacific award from
the Global Society of Health and Educational Growth, New Delhi; Best Reviewer
2015, Best Scientific Board Advisor 2016 and Best Editorial Board Member award
bestowed by the International Academy of Engineering Science and Technology,
USA. He is an active member of the Board of Studies and Academic Council of
Karnataka Veterinary Animal & Fisheries Sciences University
Bhamidipati Narasimha Murthy is a leading academic and researcher at the
ICMR’s National Institute of Epidemiology, in Chennai, He holds a Ph.D from the
International Institute of Population Science (IIPS), affiliated to Bombay University
(1985). His research focuses on mathematical statistics, operational research, clinical
research, public health, demography and vital statistics, as well as mathematical
modelling in the context of medical science and public health. He has written more
than 100 research articles published in respected national and international journals.
He also serves as an editorial board member, a reviewer and scientific board advisor
for various leading international journals. He is a life member of various academic
organisations and has received several accolades for his academic and research
excellence, including the Prof. R. N. Srivastava gold medal award, Bharat Jyothi
Award, and Best Citizen of India. He is a member of the board of studies of a number
of national universities (University of Madras, Acharya Nagarjuna University &
xxiii
xxiv About the Authors
University of Kerala) and a visiting emeritus Professor of Johns Hopkins University,
Bloomberg School of Public Health, Baltimore, Maryland, and North Carolina
University USA
