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anti-retroviral therapy is provided

Topics

hiv infections

malawi

Public Health Department, College of Medicine, University of Malawi, Blantyre, Malawi

DOI http://dx.doi.org/10.13070/rs.en.2.1324

Date 2015-03-02

Cite as Research 2015;2:1324

License CC-BY

Abstract

Prevalence and incidence are measures that are used for monitoring the occurrence of a disease.

Prevalence can be computed from readily available cross-sectional data but incidence is traditionally computed

from longitudinal data from longitudinal studies. Longitudinal studies are characterised by financial and logistical

problems where as cross-sectional studies are easy to conduct. This paper introduces a new method for

estimating HIV incidence from grouped cross-sectional sero-prevalence data from settings where antiretroviral

therapy is provided to those who are eligible according to recommended criteria for the administration of such

drugs.

Introduction

Antiretroviral therapy (ART) has helped to alleviate the suffering of AIDS patients in the world. In many countries,

patients have access to ART. In Malawi, ART is also available for free but not all HIV positive persons have access to

ART. By 2011, over 30% of HIV positive persons were on ART [1].

Incidence is a very important measure of disease occurrence. If the incidence of HIV is known, it is easy to monitor

its spread. On the other hand, prevalence alone does not give complete information about the magnitude of the

spread of HIV or any disease in general.

Consider a virulent disease like Ebola which kills after just a few days from infection. Individuals who are infected

with the Ebola virus die after a very short illness if no meaningful therapeutic intervention is available. In that case,

prevalence can never give a true picture of the extent of an Ebola epidemic since those who die from the disease are

never counted. As a result, a low prevalence of Ebola does not mean Ebola is about to be non-existent or is almost

eradicated from a community. On the other hand, the incidence of Ebola is the best measure which can be used to

monitor the disease since Ebola deaths are included in its computation. Consequently, incidence gives a true picture

of an Ebola epidemic. In the same vein, HIV incidence gives a true picture of the spread of HIV in a community.

Traditionally, incidence is computed from data from longitudinal studies. Unfortunately, there are many financial and

logistical problems associated with conducting longitudinal studies. To avoid these drawbacks, a viable alternative is

to estimate incidence from data from cross-sectional studies. Two good examples of methods for achieving this are

models by Podgor and Leske (1986) and Misiri et al (2012) [2, 3]. These models produce estimates of incidence

which are adjusted for differential mortality. Both approaches are for estimating HIV incidence where ART is not

properly rolled out in the community. It is possible to estimate the incidence of HIV from cross-sectional data from a

population where ART is provided.

The aim of this paper is to introduce a new method of estimating HIV incidence in settings where ART is provided to

HIV positive people who need it regardless of the extent of coverage of such services. This method also adjusts for

differential mortality.

Materials and Methods

Motivation

Podgor and Leske (1986) proposed a method for estimating incidence from grouped cross-sectional data [3]. In the

spirit of Podgor and Leske(1986), we proceed to motivate our approach. Let

the HIV incidence, 3 be the rate of HIV mortality in the absence of ART,

therapy,

be the rate of recruitment to ARV

Let X1, X2, X3, X4 and X5 be independent random variables where X1 is the time to death from natural causes, X2 is

the time to HIV infection, X3 is the time to death whilst HIV positive, X4 is the time to ART registration and X5 is the

time to death whilst on ART. It follows from the above description that X1, X2, ... , X5 have exponential distributions

with parameters 1, 2, 3, 4 and 5 respectively.

We will proceed by dividing the population into three strata namely: HIV negative persons, HIV positives on ART and

HIV positives who are not on ART. Denote the total proportion of HIV positives by P0, the proportion of positives who

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are not on ART by P01 and the proportion of positives who are on ART by P02. Both P01 and P02 are proportions of

the population.

Consider an interval [x, x+t]. The number of HIV positives at the end of the interval is

(1)

N1P1=N0P0S1+ N0(1-P0)S2

S1 is the probability of surviving the interval given that one entered the interval already infected.

S2 is the probability of being infected in the interval given that one was HIV negative at the beginning of the interval.

Furthermore, the number of HIV negatives at the end of the interval is

(2)

N1(1-P1)=N0(1-P0)S3

According

to

the

relationship

among

these

exponential

random

variables

[3,

4]

(3)

1

1

=1

4)

3+ 4

3+ 4

0

1

S2=1

1+ 2 3

1+ 2

1+ 2 3

0

1

and

=1

2)

1+ 2

1+ 2

In the interval [x, x+t], some people may have just been registered to receive ART but some were already registered

prior to entering the interval. Therefore the formula in (1) above does not capture the number of infected people in [x,

x+t] in a setting where ART is provided. If ART is provided, at the end of the interval there are two groups of HIV

positive individuals namely those who are not on ART and those who are on ART.

Not every infected person is eligible for ART. For example, an individual who gets infected with HIV in a 5-year

interval can never be eligible for ART as the therapy is for HIV positives who are in a reasonably advanced stage of

infection. Therefore, the number of HIV positive individuals who are on ART at the end of the interval is the sum of

old HIV positives who entered the interval already on ART and those HIV positives who are newly registered to

receive ART. This can be denoted by

(4)

N0P02S4 + N0P01S5

S4 is the probability of surviving to the end of the interval whilst on ART given than one was already on ART at the

beginning of the interval

S5 is the probability of surviving to the end of the interval having been newly recruited to receive ART given than one

was not on ART at the beginning of the interval

Using the relationship between independent exponential random variables as described in Lagakos(1976) on pages

553 through 555 [4], these probabilities are defined as follows:

4

5

1

4

3+ 4 5

3+ 4

3+ 4 5

(5)

0 02

0 01

3+ 4

3+ 4 5

(6)

1 1

0 01

3+ 4

0 (1

0 )

1+ 2

1+ 2 3

0 02

0 01

3+ 4

3+ 4 5

(7)

N1(1-P1) =N0(1-P0)S6

2015-03-27 09:27 PM

where

S6

is

the

probability

of

remaining

HIV

negative

http://www.labome.org/research/Estimating-HIV-incidence-from-grou...

having

survived

the

interval.

Now,

1

6

2)

1+ 2

1+ 2

0

1 (1

(8)

1)

0 (1

0)

1+ 2

1 0

0 1

1

1+ 2

.

1 0

0 1

1

1 0 0

1 1

From

1+ 2

this

( 2) =

3+ 4

0 01

expression

1+ 2

1 0

0 01

1

1 1

where 1- P1 > 0,

01

3+ 4

> 0 and

define

02

'(

2)

1 0

2)

1

1 1

( + 1)

2

2)

1+ 2

2 1 0

1+ 2 3

01

0 02

function

5

3+ 4

3+ 4 5

0 01

( 2)

(1

0) 2

3+ 4

3+ 4 5

as

follows

1+ 2

1+ 2 3

( )

is

1+ 2

1+ 2

> 0.

The derivative of (

1+ 2

1+ 2 3

we

has an asymptote at

'

2

2

1 0 3 1 + 2

1+ 2 3

1.

3

2 1 0

1+ 2 3

1+ 2

root on either side of the asymptote. Nevertheless, we will retain the roots of which are to the right of the asymptote

because these are the only values which satisfy the condition that. Nevertheless, we will retain the roots of ( 2 )

which are to the right of the asymptote because these are the only values which satisfy the condition that (

= 0 given

2)

> 0.

was estimated using the delta transformation. An explanation of how the formula for the

Application of the method to population-based data from the Malawi Demographic Survey 2010

Description of the data

The estimated population of Malawi in 2011 was 14,388,550 [5]. The national prevalence of HIV was 10% in 2010 [6].

The provision of ARV therapy in Malawi is overseen by the HIV Unit in the Ministry of Health and Population. By

2011, 382,953 people were on ARV therapy [1]. The remaining 1,055,902 were not on ARV therapy. In the same

year, the number of deaths due to HIV was 43,000 [1].

From the ARV Supervision database for 2004-2009 which was maintained by the HIV Unit, in 2004 there were 3,262

ART registrations [7]. By the end of 2008, a total of 20,393 HIV positive persons were recruited to receive ARV

therapy. This gives a recruitment rate ( 4 ) of 3,426 people per year on average. Studies [8, 9] conducted in Malawi

found that ART reduces mortality by 10% [8]. Therefore given HIV mortality rates, the rate of mortality among those

on ART is

= 0.9 *

3.

The age-specific HIV sero-prevalence data analysed for this paper are extracted from the database of the Malawi

Demographic and Health Survey (MDHS2010) which was conducted in 2010. The data are in Table 1 below.

3 of 6

15-19

3208

0.022

71

0.022 63

0.020

0.002

20-24

2370

0.051

122

0.051 114

0.048

0.003

25-29

2141

0.108

232

0.108 197

0.092

35

0.016

30-34

1560

0.181

283

0.181 227

0.146

56

0.036

35-39

1224

0.246

301

0.246 232

0.190

69

0.056

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40-44

870

0.247

215

0.247 155

0.178

60

45-49

817

0.193

158

0.193 95

0.116

63

0.069

0.077

50-54

295

0.129

38

0.129 25

0.085

13

0.044

In 1992, HIV was not endemic as it is today. Mortality, in general, was mainly due to causes other than HIV. As HIV

spread throughout Malawi, HIV became the leading cause of mortality. The provision of ART to HIV positives has

reversed this trend in mortality. Therefore, the mortality estimates for 1992 represent true natural mortality rates for

Malawi which are not contaminated by HIV mortality. The source of HIV mortalities is a study by Crampin et al(2002).

This study reports mortality rates for HIV persons not on ARV therapy from a study conducted in a typical rural

setting representative of an average rural area in Malawi [10]. These estimates represent HIV mortality rates in rural

Malawi in the absence of ARV therapy. Table 2 below contains the natural and HIV mortality rates.

Results

HIV

incidence

20-24, 25-29, 30-34,

Age group index (j) Age group Natural mortality rates ( 1 ) AIDS mortality rates ( 3 )

Men

Women

15-19

0.0038

0.0053

0.0471

in Table 3. The 95%

20-24

0.0041

0.0036

0.0593

25-29

0.0068

0.0068

0.0675

30-34

0.0084

0.0072

0.1354

35-39

0.0076

0.009

0.1354

estimates

40-44

0.0101

0.0089

0.1427

45-49

0.0097

0.0096

0.1427

the Newton-Raphson

method. The initial

50+

0.0097

0.0096

0.2339

each estimate is also

presented.

The

incidence

values of

plucked

into

the

NewtonRaphson algorithm were obtained by a combination of methods which include inspection, use of the R function

uniroot and numerical search procedures.

The age group with the highest incidence is the

30-34 year age group. The smallest incidence

Agegroup FOI

SE

Incidence per 5

years

95% CI for

incidence

Lower

limit

Upper

limit

and

45-49

age

groups

have

the

same

different correct to 6 decimal places. All the

15-19

0.0607 0.000358 61

60

61

20-24

0.0858 0.000779 86

84

87

25-29

114

121

intervals for the 15-19 through 45-49 age

30-34

0.1628 0.00157

163

160

166

35-39

0.1428 0.00108

143

141

145

40-44

143

146

45-49

143

146

Discussion

50-54

incidence from cross-sectional data. It is

impossible to estimate the HIV incidence for

the age group 50-54 years because the

structure of the model does not permit it.

2 ).

We tested the sensitivity of the method to the size of P01 and P02. According to our findings, big values of P01 and

P02 resulted in ( 2 ) whose roots were hard to estimate. In order to have reasonable smaller P01 and P02 for the

Newton-Raphson method to converge efficiently, both parameters (P01 and P02) must be defined as proportions of

the sample for each age group. In any case, the number of people on ART is bound to be small, therefore as a

fraction of the sample for each age group, this produces proportions which make it easy to achieve convergence

when using the Newton - Raphson algorithm.

The objective of the method is to produce incidence estimates. Therefore, defining P01 and P02 as proposed above

does not make the results of the current method unusable. The reader who wants the proportions P01 and P02 to be

defined otherwise can do so and can compute the proportions based on his own definitions from data [3].

The fact that all the confidence intervals were narrow can be explained by the size of the samples for each age

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group. All sample sizes were very big. In such cases, standard errors are very small. These affect the size of the

margin of error. Eventually, confidence intervals computed from such standard errors are likewise narrow. Besides,

the narrow confidence intervals are indicative of high precision in the estimation of FOI.

Conclusion

The novel method introduced in this paper is a very good approach for estimating HIV incidence from aggregated

data collected from settings where ART is provided to HIV infected individuals. This method is timely as it comes at a

time when provision of ART is rampant in many countries of the world.

ANNEX

Derivation of the standard error of 2

Obviously, the force of infection (FOI) 2 is the function of both P0 and P1. That is to say 2=f(P0, P1). Therefore to

find the variance of 2 we use the delta method of transformation. Using the delta method

2

= (

1 ).

0,

2 2

0

( 2) =

0) +

2 2

1

1 ).

(1)

1+ 2

1 1

1

1 0

01

3+ 4

3+ 4

02

4

1 0

5 3+ 4

3+ 4 5

2

1+ 2 3

1+ 2

Therefore

(2)

1

1 0 2

!

0

01

02

4

1 0 2

5 3+ 4

3+ 4 5

Similarly,

(3)

!

2

1+ 2

2.

1 1

1+ 2

1+ 2 3

1+ 2

1+ 2 3

1+ 2

1+ 2 3

!

1

(4)

2

0

"

#0

1 2

1 1 2

"

2

1 2

and

1 1

2

1

"

#1

"

2

The partial derivative is the quotient when the result in (2) is divided by the result in (3) above. Similarly, the partial

derivative is the quotient when the result in (4) is divided by the result in (3) above.

The variance of P0 is

0)

0 1 0

$0

1)

1 1 1

$1

Declarations

Competing interests

Acknowledgments

I am very grateful to ORC Macro International for allowing me to analyse the MDHS2010 data.

Authors' contributions

HM conceived the study, conceived the method, obtained the data, analyzed the data, drafted the manuscript and

revised it.

References

1. . HIV Unit: 2012 Global AIDS Response Progress Report:Malawi Country Report for 2010 and 2011. Lilongwe,Malawi: Ministry of

Health,Malawi Government; 2012.

2. Misiri H, Edriss A, Aalen O, Dahl F. Estimation of HIV incidence in Malawi from cross-sectional population-based sero-prevalence

data. J Int AIDS Soc. 2012;15:14 pubmed

3. Podgor M, Leske M. Estimating incidence from age-specific prevalence for irreversible diseases with differential mortality. Stat Med.

1986;5:573-8 pubmed

4. Lagakos S. A stochastic model for censored-survival data in the presence of an auxiliary variable. Biometrics. 1976;32:551-9

pubmed

id=134%3Apopulation-projections-for-malawi&catid=8&Itemid=3. ].

2015-03-27 09:27 PM

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http://www.labome.org/research/Estimating-HIV-incidence-from-grou...

6. . National Statistical Office (NSO) ORC Macro: Malawi Demographic and Health Survey 2010. Zomba: National Statistical Office

(NSO) and O. R. C. Macro; 2010.

7. Murray C, Ortblad K, Guinovart C, Lim S, Wolock T, Roberts D, et al. Global, regional, and national incidence and mortality for HIV,

tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet.

2014;384:1005-70 pubmed

publisher

8. Jahn A, Floyd S, Crampin A, Mwaungulu F, Mvula H, Munthali F, et al. Population-level effect of HIV on adult mortality and early

evidence of reversal after introduction of antiretroviral therapy in Malawi. Lancet. 2008;371:1603-11 pubmed

publisher

9. Floyd S, Molesworth A, Dube A, Banda E, Jahn A, Mwafulirwa C, et al. Population-level reduction in adult mortality after extension of

free anti-retroviral therapy provision into rural areas in northern Malawi. PLoS ONE. 2010;5:e13499 pubmed

publisher

10. Crampin A, Floyd S, Glynn J, Sibande F, Mulawa D, Nyondo A, et al. Long-term follow-up of HIV-positive and HIV-negative individuals

in rural Malawi. AIDS. 2002;16:1545-50 pubmed

ISSN : 2334-1009

2015-03-27 09:27 PM

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