Journal of Biological Dynamics

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Modelling the transmission dynamics and optimal

control strategies for HIV infection in China

Ling Xue, Yuanmei Sun, Xue Ren & Wei Sun

To cite this article: Ling Xue, Yuanmei Sun, Xue Ren & Wei Sun (2023) Modelling the
transmission dynamics and optimal control strategies for HIV infection in China, Journal of
Biological Dynamics, 17:1, 2174275, DOI: 10.1080/17513758.2023.2174275

To link to this article: https://doi.org/10.1080/17513758.2023.2174275

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JOURNAL OF BIOLOGICAL DYNAMICS
2023, VOL. 17, NO. 1, 2174275
https://doi.org/10.1080/17513758.2023.2174275

Modelling the transmission dynamics and optimal control

strategies for HIV infection in China
Ling Xuea† , Yuanmei Suna , Xue Renb† and Wei Suna
a College of Mathematical Sciences, Harbin Engineering University, Harbin, People’s Republic of China;
b College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, People’s
Republic of China

ABSTRACT ARTICLE HISTORY

In order to end the AIDS epidemic by 2030 that was put forward Received 6 April 2022
by the Joint United Nations Programme on HIV/AIDS in 2014, China Accepted 8 December 2022
needs to take more effective measures to achieve the three 90% KEYWORDS
goals (90-90-90). We establish a compartmental model to study the HIV/AIDS; equilibrium;
dynamics of HIV transmission with control strategies. The analytical mitigation strategies;
results show the existence and stability of the disease-free equilib- cost-effectiveness
rium and endemic equilibrium. An optimal control model is con-
structed to evaluate the impacts of control measures. The simulation
results show that the optimal control strategy proposed in this work
can eradicate AIDS by 2030. The cost-effectiveness analysis indicates
that the cost of the control strategy that combines screening for
latent individuals and enhancing education for unaware infected
individuals is the lowest. Our findings can provide guidance for pub-
lic health authorities on effective mitigation strategies to achieve the
goals proposed by the United Nations Program on HIV/AIDS.

1. Introduction
Since the first case of Human Immunodeficiency Virus (HIV) infection was detected in
the United States in 1981, Acquired Immune Deficiency Syndrome (AIDS) caused by
HIV infection has widely spread in different countries and regions. AIDS is a serious life-
threatening disease, and presents a great challenge to public health authorities [3,4,13]. In
2014, the United Nations Programme on AIDS (UNAIDS) proposed to achieve three 90%s
by 2020, so as to end global AIDS epidemic by 2030. The three 90% goals include: 90%
of people living with HIV need to be diagnosed, 90% of those diagnosed need to receive
antiretroviral therapy (ART), and 90% of those under treatment need to achieve viral sup-
pression [24]. At present, no vaccines are available to prevent HIV infection [2,6,23,34].
HIV/AIDS has long latent period, strong infectivity, and high death rate. Many countries
are affected by the transmission of AIDS, such as China, Cape Verde, Kenya, Lesotho,
Malawi, and Nigeria [11].

CONTACT Wei Sun sunweihit@hrbeu.edu.cn

† Contributed equally.

© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.
org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
2 L. XUE ET AL.

HIV can be transmitted through blood transmission, sexual transmission, and mother-
to-child transmission. People infected with HIV eventually show immunodeficiency syn-
drome over time. HIV aims to invade the immune system, and the infection process
includes four periods, namely, acute infectious period, latent period, pre AIDS period, and
AIDS period. Latent individuals and unaware infected individuals can transmit AIDS to
susceptible individuals, which makes it difficult to control the spread of AIDS [16]. In order
to reduce the infection transmitted by latent individuals and unaware infected individu-
als, it is essential to improve the screening rate and education rate of infected individuals
[23].
Mathematical modelling is a commonly used tool to study the spread of infectious
diseases [9,18,32,33,38,42,43,46,48]. The factors that affect the transmission of infectious
diseases can be identified by mathematical models [17]. Many mathematical models have
been developed to study the transmission dynamics of HIV. Tripathi et al. analysed the
impact of screening unconscious infected individuals [45]. Suryanto et al. proposed an
ODE model to analyse the influence of awareness, education, screening, and treatment on
the spread of AIDS, and proved that education, screening, and treatment can reduce the
number of infected individuals [44]. An AIDS model with awareness and control strat-
egy was proposed in [35], where susceptible individuals were mainly classified by gender,
and infected individuals were classified according to the level of awareness. Makinde et al.
analysed the effects of screening and treatment on the spread of HIV/AIDS infection in
the population, and incorporated the awareness and treatment for HIV infected individu-
als into the model [39]. Nyabadza et al. proposed an HIV/AIDS model with screening and
treatment, and showed that the number of aware infected individuals has a great impact on
the spread of AIDS [30]. The above works all take into account the impacts of awareness on
HIV transmission in their models. However, none of them explore how control strategies
can be implemented to achieve the goal of three 90%s and ending the AIDS epidemic by
2030 proposed by the UNAIDS in 2014. Therefore, the purpose of our work is to explore
how to achieve these goals, and provide guidance to public health authorities on containing
the spread of HIV.
Effective education and intervention for individuals at risk of HIV infection require a
large amount of resources. Since HIV infection cannot be completely cured at present,
the infected individuals who are receiving ART treatment need to take medicine for a
long term. The resources for mitigating HIV infection become more scarce since the out-
breaks of COVID-19. In this case, it is of great significance to study how to allocate limited
healthcare resources effectively to improve the efficiency of prevention and control for
AIDS.
We incorporate mitigation strategies, including providing treatment for aware infected
individuals, screening latent individuals, and educating unaware infected individuals, into
the model. We apply Pontryagin’s Maximum Principle [31] to derive optimal control strate-
gies for achieving the goals of end AIDS. The results show that the optimal control strategy
is the combination of all three control measures. The control effect is closely linked to the
weight [15,19,21,25,26].
The rest of this work is organized as follows. In Section 2, we develop a mathematical
model to study the transmission dynamics of HIV, derive the basic reproduction num-
ber, and analyse the stability of the disease free equilibrium and endemic equilibrium. We
exhibit how transimation rate, screening rate, and education rate impact the spread of HIV
 JOURNAL OF BIOLOGICAL DYNAMICS 3

through numerical simulations. In Section 3, we construct a model incorporating con-

trol strategies to find optimal control strategies for curbing the spread through numerical
simulations. In Section 4, we summarize our work, and propose future work.

2. Mathematical formulation and dynamics analysis

In this section, we introduce an HIV model and verify the feasible region of the solu-
tion. We also calculate the basic reproduction number, and analyse the stability of the
disease free equilibrium and the endemic equilibrium. In addition, we perform numerical
simulations.

2.1. Model formulation

The infected individuals are divided into latent individuals, aware individuals, and unaware
individuals. We assume that all aware infected individuals seek treatments and do not
spread the infection. On the contrary, unaware infected individuals do not know that they
are infected and are more likely to infect others. Therefore, unaware infected individu-
als are not treated unless they are screened. In addition, HIV testing has not been widely
applied, which is one of the reasons why the unaware infected individuals are not treated.
In this work, we construct a mathematical model for HIV/AIDS transmission to analyse
the spread of HIV among individuals. The population is divided into six compartments,
namely, susceptible (S), latent (E), aware (I1 ), unaware (I2 ), treated (T), and AIDS (A) com-
partments. The total number of individuals is N(t) at time t, where N(t) = S(t) + E(t) +
I1 (t) + I2 (t) + T(t) + A(t). The initial conditions are S(0), E(0), I1 (0), I2 (0), T(0), and
A(0).
Typically, all infected individuals are likely to transmit the disease. The infectivities
of infected individuals in different compartments are different. In this work, we assume
that aware individuals do not spread the infection. Let λ(t) be the force of infection for
individuals who are infected by HIV as follows

λ(t) = βεE(t) + βI2 (t),

where β is the effective contact rate for HIV transmission and ε is a coefficient represent-
ing reduced infectivity of latent individuals compared with infectious individuals. Here,
the parameter ε satisfies 0 < ε ≤ 1. The recruitment rate of susceptible individuals is .
Susceptible individuals may be infected by contacting infectious individuals at the rate
λ(t). A fraction of latent individuals, p, transfer to aware class, and 1−p of latent individ-
uals proceed to unaware infected class. Latent individuals become symptomatic infected
at the rate α. Unaware infected individuals become aware at the rate δ. Aware infected
individuals receive ART treatment at the rate ξ . The infected individuals who receive ART
treatment transfer to latent class due to treatment failure at the rate η. The infected indi-
viduals transfer to AIDS class at the rate γ . The natural death rate is μ and the mortality
rate of infected individuals is μ0 . The schematic diagram diagram is shown in Figure 1.
The state variables and the parameters are listed in Tables 1 and 2, respectively. Based
on the transmission mechanism, we propose the following ordinary differential equation
4 L. XUE ET AL.

Figure 1. Schematic diagram of HIV transmission.

model.
⎧
⎪ dS
⎪
⎪ dt =  − β(εE + I2 )S − μS,
⎪
⎪
⎪
⎪
⎪
⎪ dE
⎪
⎪ = β(εE + I2 )S − (α + μ)E,
⎪
⎪ dt
⎪
⎪
⎪
⎪ dI1
⎪
⎨ = pαE + δI2 − (μ + ξ + γ )I1 ,
dt (1)
⎪
⎪ dI2 = (1 − p)αE − (δ + γ + μ)I ,
⎪
⎪
⎪
⎪ dt
2
⎪
⎪
⎪
⎪ dT
⎪
⎪ = ξ I1 − (μ + η)T,
⎪
⎪ dt
⎪
⎪
⎪
⎪
⎩ dA = γ (I1 + I2 ) + ηT − μ0 A − μA.
dt

To facilitate calculation and analysis, let k1 = α + μ, k2 = μ + ξ + γ , k3 = μ + γ + δ,

and k4 = μ + η, then Model (1) is changed as follows

⎧
⎪ dS
⎪
⎪ =  − (βεE + βI2 )S − μS,
⎪ dt
⎪
⎪
⎪
⎪
⎪ dE
⎪
⎪ = (βεE + βI2 )S − k1 E,
⎪
⎪ dt
⎪
⎪
⎪
⎪ dI1
⎪
⎨ = pαE − k2 I1 + δI2 ,
dt (2)
⎪
⎪ dI
⎪ 2 = (1 − p)αE − k3 I2 ,
⎪
⎪
⎪ dt
⎪
⎪
⎪
⎪ dT
⎪
⎪ = ξ I1 − k4 T,
⎪
⎪ dt
⎪
⎪
⎪
⎪
⎩ dA = γ I1 + γ I2 + ηT − μ0 A − μA.
dt
 JOURNAL OF BIOLOGICAL DYNAMICS 5

Table 1. The state variables for Model (1).

Status variable Description
S The susceptible individuals
E The latent individuals
I1 The aware infected individuals
I2 The unaware infected individuals
T The HIV-infected individuals who receive ART treatment
A The AIDS individuals

Table 2. Description of parameters in Model (1).

Parameter Description Unit Value Source
 Recruitment rate of the susceptible population Year−1 1430 –
β The effective contact rate for HIV transmission Year−1 1.7649e−6 MCMC
α The rate at which latent individuals transfer to unaware or Year−1 0.333 [41]
aware infected class
ε Reduced infectivity of latent individuals Dimensionless 0.769231 [41]
p0 The minimum fraction of aware infected individuals Dimensionless 0.022591 MCMC
pmax The maximum fraction of aware infected individuals Dimensionless 0.45584 MCMC
a The constant in the function p(t) Dimensionless 0.055961 MCMC
δ The rate at which unaware individuals become aware Dimensionless 0.015697 MCMC
ξ The rate at which aware infected individuals receive Dimensionless 0.34877 MCMC
treatments
γ The rate at which unaware or aware infected individuals Dimensionless 0.056044 MCMC
progress to AIDS stage
μ0 Mortality rate of individuals with AIDS Year−1 0.2 [30]
μ Natural death rate Year−1 0.014286 [41]

2.2. Mathematical analysis

Before analysing Model (2), we derive the feasible region, the basic reproduction number,
and stability of equilibria.

2.2.1. The feasible region

Here, we analyse the non-negativity of solutions and the feasible region .

Lemma 2.1: Let the initial values of state variables in Model (2) be positive, i.e. S(0) > 0,
E(0) > 0, I1 (0) > 0, I2 (0) > 0, T(0) > 0, and A(0) > 0. The solutions of S(t), E(t), I1 (t),
I2 (t), T(t), and A(t) in Model (2) are non-negative for all t ≥ 0, and

lim sup N(t) ≤ .
t→∞ μ

Proof: Let H(t) be the minimum value of all state variables, i.e. H(t) = min{S(t), E(t), I1 (t),
I2 (t), T(t), A(t)}, for t > 0. Obviously, H(t) > 0. We assume that there exists a minimum
time t1 satisfying that H(t1 ) = 0. Suppose H(t1 ) = S(t1 ), then E(t) > 0, I1 (t) > 0, I2 (t) >
0, T(t) > 0, and A(t) > 0 for ∀t ∈ [0, t1 ). When t ∈ [0, t1 ], we obtain that
dS
=  − λ(t)S − μS
dt
≥ −λ(t)S − μS
= −(βεE + βI2 )S − μS.
6 L. XUE ET AL.

By integrating both sides of the above inequation from 0 to t, we obtain that

t
S(t) ≥ S(0)e− 0 [βεE(τ )+βI2 (τ )+μ]dτ > 0, ∀t ∈ [0, t1 ],

which contradicts with H(t1 ) = S(t1 ) = 0. Therefore, S(t) > 0, E(t) > 0, I1 (t) > 0, I2 (t) >
0, T(t) > 0, A(t) > 0 when t ≥ 0.
Next, we calculate the bounds of the state variables. Note that N(t) = S(t) + E(t) +
I1 (t) + I2 (t) + T(t) + A(t). Adding the equations of Model (2), we obtain

dN(t)
=  − μ(S(t) + E(t) + I1 (t) + I2 (t) + T(t)) − μ0 A(t) − μA(t).
dt

Because μ0 ≥ 0 and

dN(t)
=  − μN(t) − μ0 A(t),
dt
≤  − μN(t),

using the Comparison Principle Theorem [28], we obtain that


N(t) ≤ N(0)e−μt + (1 − e−μt ),
μ

where N(0) = S(0) + E(0) + I1 (0) + I2 (0) + T(0) + A(0). Hence,


lim sup N(t) ≤ .
t→∞ μ

Lemma 2.2: The feasible region of Model (2) can be defined by

 

= (S(t), E(t), I1 (t), I2 (t), T(t), A(t)) ∈ R6+ : 0 ≤ S, E, I1 , I2 , T, A ≤ N, N(t) ≤ .
μ

2.2.2. The basic reproduction number

Next, we prove the existence of the disease-free equilibrium point and compute the basic
reproduction number for Model (2).
Let the right side of Model (2) equal to zero, we obtain the following disease-free
equilibrium

Q0 = (S0 , E0 , I10 , I20 , T0 , A0 ) = , 0, 0, 0, 0, 0 .
μ
The basic reproduction number of Model (2) is obtained by the next generation matrix
approach [10]. Let Fi be newly infected individuals in compartment i and Vi be the transfer
of individuals in each compartment i, where i represents the compartment S, E, I1 , I2 , T,
 JOURNAL OF BIOLOGICAL DYNAMICS 7

and A. We define x = (S, E, I1 , I2 , T, A) = (x1 , x2 , x3 , x4 , x5 , x6 ). Model (2) can be rewritten

as follows
dx
= F − V,
dt
where
⎛ ⎞ ⎛ ⎞
0 − + (βεE + βI2 )S + μS
⎜ βεES + βI2 S ⎟ ⎜ k1 E ⎟
⎜ ⎟ ⎜ ⎟
⎜ 0 ⎟ ⎜ −pαE + k2 I1 − δI2 ⎟
F =⎜
⎜
⎟,
⎟ V =⎜
⎜
⎟.
⎟
⎜ 0 ⎟ ⎜ −(1 − p)αE + k3 I2 ⎟
⎝ 0 ⎠ ⎝ −ξ I1 + k4 T ⎠
0 −γ I1 − γ I2 − ηT + μ0 A + μA

According to the next generation matrix approach for calculating the basic reproduction
number [10], we consider the infected compartments xi , i = 2, 3, 4, 5. At the disease free
equilibrium, Q0 , we have
⎛ ⎞
  βεS0 0 βS0 0
∂F i ⎜ 0 0 0 0 ⎟
F= (Q0 ) = ⎜
⎝ 0
⎟,
∂xi 0 0 0 ⎠
0 0 0 0

and
⎛ ⎞
  k1 0 0 0
∂Vi ⎜ −pα k2 −δ 0 ⎟
V= (Q0 ) = ⎜
⎝ −(1 − p)α
⎟,
∂xi 0 k3 0 ⎠
0 −ξ 0 k4

where k1 = α + μ > 0, k2 = μ + ξ + γ > 0, k3 = μ + γ + δ > 0, and k4 = μ + η > 0.

In addition, matrices F and V satisfy the assumptions (A1)–(A5) in [10]. By calculating
the spectral radius of the next generation matrix FV −1 , we derive the basic reproduction
number, R0 , as follows

βεS0 βS0 α(1 − p)

R0 = ρ(FV −1 ) = + .
k1 k1 k3

βS0 α(1−p)
Here, βεS 0
k1 represents the number of humans infected by latent individuals, k1 k3
indicates the number of humans infected by unaware infected individuals.

2.2.3. The stability of disease-free equilibrium

First, we study the local stability of the disease free equilibrium.

Theorem 2.1: For Model (2), the disease free equilibrium, Q0 , is locally asymptotically stable
when R0 < 1 in the feasible region .
8 L. XUE ET AL.

Proof: Based on Model (2), we construct the Jacobian matrix as follows

⎛ ⎞
−(λ(t) + μ) −βεS 0 −βS 0 0
⎜ λ(t) βεS − k 0 βS 0 0 ⎟
⎜ 1 ⎟
⎜ 0 pα −k δ 0 0 ⎟
J=⎜ ⎜
2 ⎟
⎟
⎜ 0 (1 − p)α 0 −k3 0 0 ⎟
⎝ 0 0 ξ 0 −k4 0 ⎠
0 0 γ γ η −μ0 − μ
(J1 )4×4 0
= ,
(J3 )2×4 (J4 )2×2

where k1 = α + μ > 0, k2 = μ + ξ + γ > 0, k3 = μ + γ + δ > 0, and k4 = μ + η > 0.

By calculation, the roots of |rI − J(Q0 )| = 0 are the roots of |rI − J1 (Q0 )| = 0 and
|rI − J4 (Q0 )| = 0. Here, r represents the eigenvalue.
The Jacobian matrix J1 (Q0 ) is
⎛ ⎞
−μ −βεS0 0 −βS0
⎜ 0 βεS0 − k1 0 βS0 ⎟
J1 (Q0 ) = ⎜
⎝ 0
⎟.
pα −k2 δ ⎠
0 (1 − p)α 0 −k3

The characteristic equation is

 
 r+μ βεS0 0 βS0 
 
 0 r − (βεS0 − k1 ) 0 −βS0 
|rI − J1 (Q0 )| =  

 0 −pα r + k2 −δ 
 0 −(1 − p)α 0 r + k3 

= (r + k2 )(r + μ)
× [r2 + (k1 + k3 − βεS0 )r − k3 (βεS0 − k1 ) − βS0 α(1 − p)]
= 0.

Clearly, the first and second roots of |rI − J1 (Q0 )| = 0 are r1 = −k2 < 0 and r2 = −μ < 0.
Next, we mainly analyse the roots of the following equation

r2 + (k1 + k3 − βεS0 )r − k3 (βεS0 − k1 ) − βS0 α(1 − p)

= r2 + m1 r + m0
= 0. (3)

Here,

m1 = k1 + k3 − βεS0
m0 = k3 (k1 − βεS0 ) − βS0 α(1 − p)
 
βεS0 βαS0 (1 − p)
= k1 k3 1 − +
k1 k1 k3
= k1 k3 (1 − R0 ).
 JOURNAL OF BIOLOGICAL DYNAMICS 9

βS α(1−p)
When R0 < 1, it is easy to prove that m1 > 0 and m0 > 0. Here, R0 = βεS k1 +
0 0
k1 k3 .
By the Routh–Herwitz criteria [8], the roots of Equation (3) have negative real parts.
For J4 (Q0 ),
|rI − J4 (Q0 )| = (r + k4 )(r + μ0 + μ) = 0.
Obviously, the eigenvalues of J4 (Q0 ) are r5 = −k4 < 0 and r6 = −μ0 − μ < 0.
In summary, the disease free equilibrium, Q0 , is locally asymptotically stable in when
R0 < 1. 

Next, we explore the globally asymptotic stability of the disease free equilibrium.

Theorem 2.2: For Model (2), when R0 < 1, the disease-free equilibrium point, Q0 is globally
asymptotically stable.

Proof: By Theorem 2.1 of [40], we construct a Lyapunov function as follows

L = (εk3 + α(1 − p))E + k1 I2 .

Obviously, L ≥ 0.
Next, we take the derivative of L.
dL dE dI2
= (εk3 + α(1 − p)) + k1
dt dt dt
= (εk3 + α(1 − p))(βεSE + βSI2 − k1 E) + α(1 − p)k1 E − k1 k3 I2
= (εk3 + α(1 − p))(βεSE + βSI2 ) − k1 k3 εE − k1 k3 I2
 
≤ (εk3 + α(1 − p))( βεE + βI2 ) − k1 k3 εE − k1 k3 I2
μ μ
= (εE + I2 )k1 k3 (R0 − 1).

When R0 < 1, dL
dt < 0. Therefore, the largest invariant set contained in
 
dL
(S, E, I1 , I2 , T, A) ∈ : =0
dt
is {Q0 }. According to the Lasalle’s invariance principle [20], the disease-free equilibrium
Q0 is globally asymptotically stable in when R0 < 1. 

2.2.4. Endemic equilibrium and stability of endemic equilibrium

In this section, we prove the existence of a unique endemic equilibrium point Q∗ in
Model (2). Let Q∗ = (S∗ , E∗ , I1∗ , I2∗ , T ∗ , A∗ ).
From the second to sixth equations in Model (2), we have
 
∗ k3 ∗ ∗ pk3 + (1 − p)δ ξ(pk3 + (1 − p)δ) ∗
E = I 2 , I1 = I2 ∗ , T ∗ = I2 ,
(1 − p)α (1 − p)k2 (1 − p)k2 k4
   
∗ γ I2∗ pk3 + δ(1 − p) ηξ I2 ∗ pk3 + δ(1 − p)
A = +1 + ,
μ + μ0 k2 (1 − p) (μ + μ0 )k4 k2 (1 − p)
10 L. XUE ET AL.

 (R0 − 1) μα(1 − p)S0

S∗ = k1 k3 I2 ∗ R0
, I2∗ = .
μ+ k1 k3 R0
α(1−p) S0

Hence, we obtain that I2∗ > 0 iff R0 > 1. Based on the above analysis, Model (2) has a
unique endemic equilibrium, Q∗ when R0 > 1.
Next, we study the global stability of the endemic equilibrium, Q∗ .

Theorem 2.3: For Model (2), if R0 > 1, the endemic equilibrium Q∗ is globally asymptoti-
cally stable.

Proof: We define a Lyapunov function [22] Ṽ as follows

S E I1
Ṽ = S − S∗ − S∗ ln + B E − E∗ − E∗ ln + C I1 − I1∗ − I1∗ ln
S∗ E∗ I1∗
I2 T
+ D I2 − I2∗ − I2∗ ln + G T − T ∗ − T ∗ ln .
I2∗ T∗

where B, C, D, and G are nonnegative constants. The function Ṽ is positive definite and has
the first derivative. Next, we verify that Ṽ is positive definite. All parameters of Model (2)
are bounded and positive. Obviously, Ṽ(Q∗ ) = 0. When S > 0, E > 0, I1 > 0, I2 > 0, T >
0, A > 0 and S = S∗ , E = E∗ , I1 = I1 ∗ , I2 = I2 ∗ , T = T ∗ , A = A∗ , we define

Ṽ(S, E, I1 , I2 , T) = h(S) + Bh(E) + Ch(I1 ) + Dh(I2 ) + Gh(T),

where h(S) = S − S∗ − S∗ ln SS∗ , h(E) = E − E∗ − E∗ ln EE∗ , h(I1 ) = I1 − I1 ∗ − I1 ∗ ln II11∗ ,

h(I2 ) = I2 − I2 ∗ − I2 ∗ ln II22∗ , and h(T) = T − T ∗ − T ∗ ln TT∗ . Because h(S∗ ) = 0 and h (S) =
∗
1 − SS , h(S) ≥ 0. Similarly, h(E) ≥ 0, h(I1 ) ≥ 0, h(I2 ) ≥ 0, and h(T) ≥ 0.
Based on Model (2),

S∗ E∗ I1 ∗
Ṽ = 1 − S +B 1− E +C 1− I1
S E I1
I2 ∗ T∗
+D 1− I2 + G 1 − T
I2 T
S∗ E∗
= 1− ( − β (εE + I2 ) S − μS) + B 1 − (β (εE + I2 ) S − (α + μ) E)
S E
I1 ∗  
+C 1− pαE + δI2 − (μ + ξ + γ ) I1
I1
I2 ∗   
+D 1− 1 − p αE − (δ + γ + μ) I2
I2
T∗
+G 1− (ξ I1 − (μ + η) T)
T
S∗  
= 1− βεE∗ S∗ + βI2 ∗ S∗ + μS∗ − (βεES + βI2 S + μS)
S
 JOURNAL OF BIOLOGICAL DYNAMICS 11

E∗ βεE∗ S∗ + βI2 ∗ S∗
+B 1− βεES + βI2 S − E
E E∗
I1 ∗ pαE∗ + δI2 ∗
+C 1− pαE + δI2 − I1
I1 I1∗
   
I2 ∗   1 − p αE∗
+D 1− 1 − p αE − I2
I2 I2 ∗
T∗ ξ I1 ∗
+G 1− ξ I1 − T .
T T∗

Let
S E I1 I2 T
= x, = y, = z, = m, = n.
S∗ E∗ I1 ∗ I2 ∗ T∗
Then

(1 − x)2 1   1
Ṽ = −μS∗ + βεS∗ E∗ 1 − 1 − xy + βI2∗ S∗ 1 − (1 − xm)
x x x
1   1  
+ BβεS∗ E∗ 1 − xy − y + BβI2∗ S∗ 1 − xm − y
y y
1   1
+ CpαE∗ 1 − y − z + CδI2∗ 1 − (m − z)
z z
  1   1
+ Dα 1 − p E∗ 1 − y − m + Gξ I1∗ 1 − (z − n)
m n
(1 − x)2
= −μS∗ + [βεS∗ E∗ + βI2∗ S∗ + BβεS∗ E∗ + BβI2∗ S∗ + CpaE∗
x
   
+ CδI2∗ + Dα 1 − p E∗ + Gξ I1∗ ] + xy −βεS∗ E∗ + BβεS∗ E∗
1 
+ −βεS∗ E∗ − βI2∗ S∗
x
   
+ y βεS∗ E∗ − BβεS∗ E∗ − BβI2∗ S∗ + CpαE∗ + Dα 1 − p E∗
     
+ m βI2 ∗ S∗ + CδI2∗ − Dα 1 − p E∗ + xm −βI2∗ S∗ + BβI2∗ S∗
  xm y m
+ z −CpαE∗ − CδI2 ∗ + Gξ I1∗ − xBβεS∗ E∗ − BβI2 ∗ S∗ − CαpE∗ − CδI2 ∗
y z z
y   z
− Dα 1 − p E∗ − nGξ I1 ∗ − Gξ I1∗ . (4)
m n
Based on [22], we let the coefficients of xy, y, m, and z equal to zero and obtain that
⎧
⎪
⎪ −βεS∗ E∗ + BβεS∗ E∗ = 0,
⎪
⎪
⎨βεS∗ E∗ − BβεS∗ E∗ − BβI ∗ S∗ + CpαE∗ + Dα(1 − p)E∗ = 0,
2
∗
(5)
⎪βI2 S + CδI2 − Dα(1 − p)E∗ = 0,
⎪
∗ ∗
⎪
⎪
⎩−CpαE∗ − CδI ∗ + Gξ I ∗ = 0.
2 1
12 L. XUE ET AL.

Solving Equation (5), we get

βI2∗ S∗
B = 1, C = 0, D= , G = 0,
α(1 − p)E∗

where p = 1.
With the above B, C, D, and G, the Lyapunov function Ṽ is

S E βI ∗ S∗ I2
Ṽ = S − S∗ − S∗ ln + E − E∗ − E∗ ln +  2  I2 − I2∗ − I2∗ ln .
S∗ E∗ α 1 − p E∗ I2∗

Thus,

(1 − x)2
Ṽ = −μS∗ + [βεS∗ E∗ + βI2∗ S∗ + BβεS∗ E∗ + BβI2∗ S∗ + CpaE∗ + CδI2∗
x
1
+ Dα(1 − p)E∗ + Gξ I1∗ ] + (−βεS∗ E∗ − βI2∗ S∗ )
x
+ CpαE∗ + Dα(1 − p)E∗ − xBβεS∗ E∗
xm y m y   z
− BβI2 ∗ S∗ − CαpE∗ − CδI2 ∗ − Dα 1 − p E∗ − nGξ I1 ∗ − Gξ I1∗
y z z m n
 
(1 − x)2 βI ∗ S∗  
= −μS∗ + 2βεS∗ E∗ + 2βI2∗ S∗ +  2  ∗ α 1 − p E∗
x α 1−p E
1 
+ −βεS∗ E∗ − βI2∗ S∗
x
xm ∗ ∗ y βI ∗ S∗  
− xβεS∗ E∗ − βI2 S −  2  α 1 − p E∗
∗
y mα 1−p E
(1 − x)2 1 1 xm y
= −μS∗ + βεS∗ E∗ 2 − − x + βI2 ∗ S∗ 3 − − − .
x x x y m

Because the arithmetic mean is greater than or equal to the geometrical mean, 2 − x1 − x ≤
y
0 and 3 − x1 − xm 1
y − m ≤ 0 for x, y, m > 0. Here, 2 − x − x = 0 iff x = 1, and 3 − x −
1

xm y
y − m = 0 iff x = 1 and y = m. Therefore, Ṽ ≤ 0 for x, y, m > 0, and Ṽ = 0 iff x = 1
and y = m. According to the LaSalle’s Invariable Principle [20], it is easy to prove that the
endemic equilibrium Q∗ is globally asymptotically stable in . In summary, the endemic
equilibrium Q∗ is globally asymptotically stable when R0 > 1. 

Since the endemic equilibrium Q∗ is globally asymptotically stable, Q∗ is locally asymp-

totically stable when R0 > 1.

2.3. Numerical simulations

The HIV case data is obtained from the Chinese Center for Disease Control and Pre-
vention [7]. We mainly consider the spread of HIV among people between 15 and 60
years old and fit the number of infected individuals to Model (2). We apply the annual
 JOURNAL OF BIOLOGICAL DYNAMICS 13

Figure 2. The global sensitivity analysis of parameters ε, p, ξ , γ , δ, and β.

number of new HIV cases in China from 2002 to 2019 by the Markov chain Monte Carlo
(MCMC) method to estimate the unknown parameters in Model (2) as shown in Table 2.
Moreover, we use the Partial Rank Correlation Coefficients (PRCC) to study the global
sensitivity of the parameters of Model (2). The goal is to identify the most important
parameter that affects HIV transmission. The PRCCs of the parameters with respect to
R0 are listed in Figure 2. Our results show that parameters ε and β are positively cor-
related with R0 , and parameters p, ξ , γ , and δ are negatively correlated. Moreover, we
find that parameters β and p are the most sensitive to R0 . Hence, reducing the value
of parameter β and increasing the value of parameter p will effectively mitigate HIV
spread.
We use the AIDS data in 2002 as the initial conditions and assume that S0 = S(0) =
924, 860, 000, E0 = E(0) = 770, 000, I10 = I1 (0) = 40, 000, I20 = I2 (0) = 39, 000, T0 =
T(0) = 560, and A0 = A(0) = 0. In the following numerical simulations, we choose the
function p = p(t) = (p0 − pmax )e−at + pmax to fit the fraction of latent individuals that
become aware. Here, p0 is the minimum fraction of aware infected individuals, pmax is the
maximum fraction of aware infected individuals, and a is a constant.
The stability of the model is shown in Figures 3 and 4. Figure 3 shows the stability of
the endemic equilibrium point. When R0 > 1, the endemic equilibrium point tends to be
stable. The number of susceptible individuals, S(t), decreases first, then tends to be stable.
The trends of E, I1 , I2 , and T are similar. They all increase obviously at the early stage, then
tend to be stable. In Figure 4, the disease free equilibrium point tends to be stable when
R0 < 1. The number of susceptible individual increases to a larger level, then tends to be
stable, while the numbers of exposed, unaware infected, and aware infected individuals
decrease first and tend to be stable afterwards.
In the following numerical simulations, we use the parameters in Table 2. Figure 5 shows
that the number of unaware infected and treated individuals increase from 2002 to 2019.
The numbers of latent individuals decreases from 2002 to 2011, then slowly increases from
2012. In addition, we find that the number of aware infected individuals increases from
2002 to 2005, then this number remains almost the same from 2006 to 2019. Particularly,
14 L. XUE ET AL.

Figure 3. The stability analysis when the parameters are β = 1.7649e−6 , δ = 0.015697, γ = 0.056044,
ξ = 0.34877, p0 = 0.022591, a = 0.055961, pmax = 0.45584, and R0 = 1.8281 > 1. (a) The number of
susceptible individuals (S) varying with time. (b) The number of latent individuals (E) varying with time.
(c) The number of aware infected individuals (I1 ) varying with time. (d) The number of unaware infected
individuals (I2 ) varying with time. (e) The number of individuals who receive ART treatment individuals
(T) varying with time.

we find that the total number of I1 and T tends to be 800,000 at the end of 2019, which is
close to the data.
Next, we analyse the impact of a single parameter on the AIDS epidemic. We inves-
tigate the effects of the transmission rate, β, on the epidemic. In Figure 6, the number
of infected individuals during the latent period of AIDS can be effectively controlled by
reducing the transmission rate. Moreover, when the transmission rate is β = 0.6e−6 , the
epidemic dies out more quickly. The changes in the transmission rate indicate that the pub-
lic health authorities need to continue strengthening control efforts to suppress the spread
of HIV infection. Therefore, it is necessary to improve the awareness of latent individuals.
Figure 7 shows the impacts of changing p0 and pmax on the number of latent individuals.
We find that the number of latent individuals does not change much when the value of
p0 is between 0.022591 and 0.4. However, the value of pmax has a great influence on the
number of latent individuals, that is, the larger the value of pmax , the smaller the number
of latent individuals. Figure 8 explores the effect of the rate at which unaware individu-
als become aware, δ, on the number of infected individuals. We find that the numbers
of latent individuals, unaware infected, aware infected individuals, and treated individ-
uals decrease significantly when the value of δ is increased from 0.01 to 0.2. Moreover,
the number of latent individuals increases from 2010 to 2030 when the value of δ is very
small. The number of latent individuals decreases till the end of 2030 when δ is large
enough.
 JOURNAL OF BIOLOGICAL DYNAMICS 15

Figure 4. The stability analysis when the parameters are β = 1.0e−06 , δ = 0.01, γ = 0.15, ξ =
0.34877, p0 = 0.022591, a = 0.055961, pmax = 0.45584, and R0 = 0.7699 < 1. (a) The number of sus-
ceptible individuals (S) varying with time. (b) The number of latent individuals (E) varying with time. (c)
The number of aware infected individuals (I1 ) varying with time. (d) The number of unaware infected
individuals (I2 ) varying with time. (e) The number of individuals who receive ART treatment individuals
(T) varying with time.

Figure 5. The number of exposed, unaware infected, aware infected, and treated individuals varying
with time. The parameters in Table 2 are used in the simulation.

To evaluate the combined effect of β, pmax , and δ on the spread of HIV, we simu-
late the number of infected individuals with different combinations of these three values
as is shown in Figure 9. The numbers of latent individuals and unaware individuals are
decreasing with the decrease of β and the increase of pmax and δ as shown in Figure 9(a,c).
16 L. XUE ET AL.

Figure 6. The number of latent individuals, E, varying with β.

Figure 7. The number of latent individuals, E, varying with p0 and pmax .

However, the number of aware individuals increases from 2002 to 2006, then decreases
from 2007 to 2019 when β ≤ 1.5649e−6 , pmax ≥ 0.5, and δ ≥ 0.03 as shown in Figure 9(b).
From Figure 9(d), we find that with the decrease of β and the increase of pmax and δ,
the number of infected individuals receiving ART treatment decreases from 2002 to 2015,
while the situation is opposite after 2015.
Figure 10 explores the effect of the transmission rate, β, the maximum fraction of
aware infected individuals, pmax , and the rate at which unaware individuals become
aware, δ, on the number of infected individuals. From Figure 10(a–d), we find that
reducing transmission rate, increasing the maximum fraction of aware infected individ-
uals and the rate at which unaware individuals become aware can effectively mitigate
the spread of AIDS. Particularly, the numbers of latent, aware, and unaware individuals
become zero by the end of 2030 when β = 1e−6 , pmax = 0.7, and δ = 0.14. Therefore, we
can eradicate AIDS by reducing transmission rate and raising the awareness of infected
individuals.
 JOURNAL OF BIOLOGICAL DYNAMICS 17

Figure 8. The effect of the rate at which unaware infected individuals become aware, δ, on the number
of infected individuals. (a) δ = 0.01. (b) δ = 0.05. (c) δ = 0.1. (d) δ = 0.2.

From the above numerical simulations, the basic reproduction number R0 = 1.8281 >
1 when the parameters in Table 2 are applied in the simulation. If the current control
remains unchanged, HIV outbreaks will continue, and eventually approach the endemic
equilibrium point (see Figure 3). In addition, we find that the fraction of latent individuals
who transfer to aware individuals class, p, and the rate at which unaware infected individ-
uals become aware, δ, have a great impact on reducing the number of infected individuals.
When more HIV infected individuals are screened or become aware, the number of indi-
viduals receiving ART increases. This leads to a significant reduction in the incidence of
HIV, which in turn reduces the burden on the health system [14]. Therefore, it is necessary
to increase HIV screening rate and enhance media campaigns to increase the awareness
about HIV infection.

3. Optimal control
We extend our model by including multiple control strategies. We prove the existence,
boundedness and uniqueness of the optimal solution and apply the Pontryagin’s Maximum
18 L. XUE ET AL.

Figure 9. The number of infected individuals I1 , I2 , E, and T when the values of parameters β, δ, and
pmax are varying. (a) The effect of changing β, δ, and pmax on the number of latent individuals (E). (b) The
effect of changing β, δ, and pmax on the number of aware individuals (I1 ). (c) The effect of changing β,
δ, and pmax on the number of unaware individuals (I2 ). (d) The effect of changing β, δ, and pmax on the
number of infected individuals receiving ART treatment (T).

Principle [31] to compute the optimal solution. Moreover, we analyse the efficiency and the
costs of the control strategies and provide the most economical control strategy.

3.1. Control model formulation

Model (6) has six state variables, that is, S, E, I1 , I2 , T, and A, and three control variables,
namely, u1 (t), u2 (t), and u3 (t). Here, u1 (t) represents the intensity of screening latent indi-
viduals, u2 (t) represents the intensity of education for unaware infected individuals, and
u3 (t) represents the treatments for aware infected individuals. The control set is

= {(u1 , u2 , u3 )|ui (t) ∈ L∞ [0, tf ], 0 ≤ ui (t) ≤ ci , 0 < ci ≤ 1, i = 1, 2, 3},

where tf is the end time of implementing controls.

 JOURNAL OF BIOLOGICAL DYNAMICS 19

Figure 10. The variation trend of the number of the infected individuals under different parameter val-
ues of β, pmax , and δ. (a) β = 1.5649e−6 , pmax = 0.5, and δ = 0.03. (b) β = 1.4649e−6 , pmax = 0.55,
and δ = 0.06. (c) β = 1.2e−6 , pmax = 0.65, and δ = 0.1. (d) β = 1e−6 , pmax = 0.7, and δ = 0.14.

Then, the optimal control model is described as follows

⎧
⎪ dS
⎪
⎪ =  − (βεE + βI2 )S − μS
⎪ dt
⎪
⎪
⎪
⎪
⎪ dE
⎪
⎪ = (βεE + βI2 )S − (α + μ)E − u1 (t)E
⎪
⎪ dt
⎪
⎪
⎪
⎪ dI1
⎪
⎨ = pαE + δI2 − (μ + ξ + γ )I1 + u1 (t)E + u2 (t)I2 − u3 (t)I1
dt (6)
⎪
⎪ dI
⎪ 2 = (1 − p)αE − (δ + γ + μ)I2 − u2 (t)I2
⎪
⎪
⎪ dt
⎪
⎪
⎪
⎪ dT
⎪
⎪ = ξ I1 − (η + μ)T + u3 (t)I1
⎪
⎪ dt
⎪
⎪
⎪
⎪
⎩ dA = γ I1 + γ I2 + ηT − μ0 A − μA.
dt
The initial conditions satisfy

S(0) ≥ 0, E(0) ≥ 0, I1 (0) ≥ 0, I2 (0) ≥ 0, T(0) ≥ 0, A(0) ≥ 0. (7)

20 L. XUE ET AL.

We seek to minimize the number of infected individuals and the cost of applying screening,
education and treatment controls. Thus, the objective function is given by
 tf  
n1 n2 n3
J(u1 , u2 , u3 ) = m1 E + m2 I1 + m3 I2 + u21 (t) + u22 (t) + u23 (t) dt, (8)
0 2 2 2

where m1 , m2 , and m3 represent the weights for the numbers of latent individuals, aware
infected individuals and unaware infected individuals, respectively. The weights n1 , n2 , and
n3 measure the costs of control variables u1 , u2 , and u3 , respectively.
First, we apply the method in [27,47] to prove the existence of optimal solution.

Theorem 3.1: For the objective function J(u), there exists an optimal solution u∗ =
{u∗1 , u∗2 , u∗3 } ∈ such that

J(u∗ ) = J(u∗1 , u∗2 , u∗3 ) = min J(u1 , u2 , u3 ).

u∈

Proof: We prove the existence of an optimal strategy u∗ . By definition, the control set
is closed and convex. The integration of the function J is also concave on . The control
system is bounded, which implies the compactness of the optimal control. Furthermore,
there exists a constant ζ > 1, and positive values C1 , and C2 , such that
 ζ
J(u1 , u2 , u3 ) ≥ C1 |u1 (t)|2 + |u2 (t)|2 + |u3 (t)|2 2 − C2 ,

which proves the existence of the optimal control. 

In order to find the optimal solution, we construct the following Lagrange function L
and Hamiltonian function H
n1 2 n2 n3
L(t, φ, u) = m1 E + m2 I1 + m3 I2 + u1 (t) + u22 (t) + u23 (t),
2 2 2

n1 2 n2 n3
H(t, φ, u) = m1 E + m2 I1 + m3 I2 + u (t) + u22 (t) + u23 (t)
2 1 2 2
+ λ1 ( − (βεE + βI2 )S − μS) + λ2 ((βεE + βI2 )S − (α + μ)E − u1 (t)E)
+ λ3 (pαE + δI2 − (μ + ξ + γ )I1 + u1 (t)E + u2 (t)I2 − u3 (t)I1 )
+ λ4 ((1 − p)αE − (δ + γ + μ)I2 − u2 (t)I2 )
+ λ5 (ξ I1 − (η + μ)T + u3 (t)I1 ) + λ6 (γ I1 + γ I2 + ηT − μ0 A − μA),

where φ = (S, E, I1 , I2 , T, A)T , u = (u1 , u2 , u3 )T , and λi (t), i = 1, 2, . . . , 6, are adjoint vari-

ables.
Second, we apply the Pontryagin’s Maximum Principle [31] to compute the optimal
solution.

Theorem 3.2: For Model (6), if the control variables (u∗1 , u∗2 , u∗3 ) satisfy that H(t, φ, u∗ ) <
H(t, φ, u), the states variables S∗∗ , E∗∗ , I1∗∗ , I2∗∗ , T ∗∗ , and A∗∗ are the solutions. Thus, there
 JOURNAL OF BIOLOGICAL DYNAMICS 21

exist adjoint variables, λi (t), i = 1, 2, . . . , 6 satisfying

λ1 = λ1 (βεE + βI2 + μ) − λ2 (βεE + βI2 ),

λ2 = −m1 + λ1 βεS − λ2 (βεS − (α + μ) − u1 (t)) − λ3 (pα + u1 (t)) − λ4 (1 − p)α,
λ3 = −m2 + λ3 (μ + ξ + γ + u3 (t)) − λ5 (ξ + u3 (t)) − λ6 γ ,
λ4 = −m3 + λ1 βS − λ2 βS − λ3 (δ + u2 (t)) + λ4 (δ + γ + μ + u2 (t)) − λ6 γ ,
λ5 = λ5 (η + μ) − λ6 η,
λ6 = λ6 (μ0 + μ).
(9)
The boundary conditions are

λi (tf ) = 0, i = 1, 2, . . . , 6.

The optimal controls u∗1 , u∗2 , and u∗3 are

⎧
⎪ ∗
⎨u1 (t) = min{max{0, u1 }, 1},
c

u∗2 (t) = min{max{0, uc2 }, 1},

⎪
⎩ ∗
u3 (t) = min{max{0, uc3 }, 1},

(λ2 − λ3 )E∗∗ c (λ4 − λ3 )I2∗∗ (λ3 − λ5 )I1∗∗

where uc1 = , u2 = , and uc3 = . Hence, the optimal
n1 n2 n3
solution is
⎧
⎨ 0, if uci ≤ 0,
u∗i = uc , if 0 < uci < 1,
⎩ i
1, if uci ≥ 1,
where i = 1, 2, 3.

Proof: According to the existence of optimal control solutions based on the Pontryagin’s
Maximum Principle, we derive the differential equation system of the Hamiltonia function
H as follows
⎧ dλ ∂H
⎪
⎪
1
=− = λ1 (βεE + βI2 + μ) − λ2 (βεE + βI2 ),
⎪
⎪ ∂S
⎪
⎪ dt
⎪
⎪ dλ 2 ∂H
⎪
⎪ =− = −m1 + λ1 βεS − λ2 (βεS − (α + μ) − u1 (t))
⎪ dt
⎪ ∂E
⎪
⎪
⎪
⎪ −λ3 (pα + u1 (t)) − λ4 (1 − p)α,
⎪
⎪
⎪
⎪ dλ 3 ∂H
⎨ =− = −m2 + λ3 (μ + ξ + γ + u3 (t)) − λ5 (ξ + u3 (t)) − λ6 γ ,
dt ∂I1
⎪
⎪ dλ4 ∂H
⎪
⎪ =− = −m3 + λ1 βS − λ2 βS − λ3 (δ + u2 (t))
⎪
⎪ dt ∂I2
⎪
⎪
⎪
⎪ +λ4 (δ + γ + μ + u2 (t)) − λ6 γ ,
⎪
⎪
⎪
⎪ dλ 5 ∂H
⎪
⎪ =− = λ5 (η + μ) − λ6 η,
⎪
⎪ dt ∂T
⎪
⎩ dλ6 = − ∂H = λ (μ + μ),
⎪
6 0
dt ∂A
and λi (tf ) = 0, i = 1, 2, . . . , 6.
22 L. XUE ET AL.

Next, for the control variables u1 , u2 , and u3 in the control set , we derive the partial
derivatives of the Hamiltonian function with respect to u1 , u2 , and u3 as follows

∂H
= n1 u1 (t) + (λ3 − λ2 )E∗∗ ,
∂u1
∂H
= n2 u2 (t) + (λ3 − λ4 )I2∗∗ ,
∂u2
∂H
= n3 u3 (t) + (λ5 − λ3 )I1∗∗ .
∂u3
∂H ∂H ∂H
Let ∂u1 = 0, ∂u2 = 0, and ∂u3 = 0, we obtain
⎧
⎪ (λ2 − λ3 )E∗∗
⎪
⎪ u∗1 (t) = ,
⎪
⎪ n1
⎨ ∗∗
(λ4 − λ3 )I2
u∗2 (t) = ,
⎪
⎪ n2
⎪
⎪ ∗∗
(λ3 − λ5 )I1
⎪
⎩u∗3 (t) = .
n3
Since the control variable 0 ≤ ui ≤ 1, i = 1, 2, 3, the optimal controls are
⎧    
⎪
⎪ ∗ (λ2 − λ3 )E∗∗
⎪
⎪ u1 (t) = min max 0, ,1
⎪
⎪   n1  
⎨ ∗∗
(λ4 − λ3 )I2
u∗2 (t) = min max 0, ,1
⎪
⎪   n2  
⎪
⎪ ∗∗
(λ3 − λ5 )I1
⎪
⎪
⎩u∗3 (t) = min max 0, ,1 .
n3

Next, we show that the solutions of Model (6) satisfying initial condition (7) are bounded
by applying the method in [12,36].

Theorem 3.3: The corresponding absolutely continuous solution (S(t), E(t), I1 (t), I2 (t), T(t),
A(t)) to Model (6) is defined on the entire interval [0, tf ] for any admissible controls
(u1 (t), u2 (t), u3 (t)). The state variables S(t), E(t), I1 (t), I2 (t), T(t), A(t) satisfy the following
inequalities

   
0 ≤ S(t) ≤ , 0 ≤ E(t) ≤ , 0 ≤ I1 (t) ≤ , 0 ≤ I2 (t) ≤ ,
μ μ μ μ
 
0 ≤ T(t) ≤ , 0 ≤ A(t) ≤ .
μ μ

Proof: We assume that the solution (S(t), E(t), I1 (t), I2 (t), T(t), A(t)) of Model (6) is
defined in the interval [0, t ∗ ), which is the maximum interval of existence. Without loss of
generality, we assume that t ∗ ≤ tf . According to Model (6) and the conditions 0 ≤ ui ≤ 1,
i = 1, 2, 3, the nonnegativity of the solutions (S(t), E(t), I1 (t), I2 (t), T(t), A(t)) is verified
 JOURNAL OF BIOLOGICAL DYNAMICS 23

in Lemma 2.2. Simultaneously, we obtain the upper bound of the solution of Model (6) by
Lemma 2.2, that is,

0 ≤ S(t), E(t), I1 (t), I2 (t), T(t), A(t) ≤ .
μ
Therefore, the solutions of Model (6) satisfying initial condition (7) are bounded. 

Next, we apply the method in [35] to prove the uniqueness of optimal control.

Theorem 3.4: The solution of the optimal system (6) is unique for sufficiently small interval
[t0 , tf ].

Proof: We suppose that (S, E, I1 , I2 , T, A, λ1 , λ2 , λ3 , λ4 , λ5 , λ6 ) and (S̄, Ē, I¯1 , I¯2 , T̄, Ā, λ̄1 , λ̄2 ,
λ̄3 , λ̄4 , λ̄5 , λ̄6 ) are two solutions of models (6) and (9). Let S = eθ t p1 , E = eθ t p2 , I1 = eθ t p3 ,
I2 = eθ t p4 , T = eθ t p5 , A = eθ t p6 , λ1 = e−θ t q1 , λ2 = e−θ t q2 , λ3 = e−θ t q3 , λ4 = e−θ t q4 ,
λ5 = e−θ t q5 , λ6 = e−θ t q6 , S̄ = eθ t p̄1 , Ē = eθ t p̄2 , I¯1 = eθ t p̄3 , I¯2 = eθ t p̄4 , T̄ = eθ t p̄5 , Ā =
eθ t p̄6 , λ̄1 = e−θ t q̄1 , λ̄2 = e−θ t q̄2 , λ̄3 = e−θ t q̄3 , λ̄4 = e−θ t q̄4 , λ̄5 = e−θ t q̄5 , and λ̄6 = e−θ t q̄6 ,
where θ > 0 is to be determined. pi , qi , p̄i , and q̄i (i = 1, 2, . . . , 6) are variables with respect
to t.
Moreover, we have
   
∗ (q2 − q3 )p2
u1 (t) = min max 0, ,1
n1
   
∗ (q4 − q3 )p4
u2 (t) = min max 0, ,1
n2
   
∗ (q3 − q5 )p3
u3 (t) = min max 0, ,1
n3

and
   
(q¯2 − q̄3 )p̄2
u¯∗1 (t) = min max 0, ,1
n1
   
(q̄4 − q̄3 )p̄4
u¯∗2 (t) = min max 0, ,1
n2
   
¯ ∗ (q̄3 − q̄5 )p̄3
u3 (t) = min max 0, ,1 .
n3

Next, we substitute the values of S, E, I1 , I2 , T, A, λ1 , λ2 , λ3 , λ4 , λ5 , λ6 into Equations (6)

and (9). Then, we have

p1 + θp1 = e−θ t − (βεp2 + βp4 )p1 eθ t − μp1 ,

(q2 − q3 )p2
p2 + θp2 = (βεp2 + βp4 )p1 eθ t − (α + μ)p2 − p2 ,
n1
(q2 − q3 )p2
p3 + θp3 = pαp2 + δp4 − (μ + ξ + γ )p3 + p2
n1
24 L. XUE ET AL.

(q4 − q3 )p4 (q3 − q5 )p3

+ p4 − p3 ,
n2 n1
(q4 − q3 )p4
p4 + θp4 = (1 − p)αp2 − (δ + γ + μ)p4 − p4 ,
n2
(q3 − q5 )p3
p5 + θp5 = ξ p3 − (η + μ)p5 + p3 ,
n1
p6 + θp6 = γ p3 + γ p4 + ηp5 − μ0 p6 − μp6 ,
q1 − θq1 = q1 (βεp2 eθ t + βp4 eθ t + μ) − q2 eθ t (βεp2 + βp4 ),
(q2 − q3 )p2
q2 − θq2 = −m1 eθ t + q1 p1 βεeθ t − q2 (βεp1 eθ t − (α + μ) − p2 )
n1
(q2 − q3 )p2
− q3 (pα + p2 ) − q4 (1 − p)α,
n1
(q3 − q5 )p3 (q3 − q5 )p3
q3 − θq3 = −m2 eθ t + q3 (μ + ξ + γ + p3 )−q5 (ξ + p3 )−q6 γ ,
n1 n1
(q4 − q3 )p4 (q4 − q3 )p4
q4 − θq4 = −m3 eθ t − q3 (δ + p4 ) + q4 (δ+γ + μ + + p4 )−q6 γ ,
n2 n2
q5 − θq5 = q5 (η + μ) − q6 η,
q6 − θq6 = q6 (μ0 + μ).

The equations for S and S̄, E and Ē, I1 and I¯1 , I2 and I¯2 , T and T̄, A and Ā are subtracted.
Each equation is multiplied by an appropriate function and integrated from t0 to tf . Thus,
 tf  tf
(u∗1 − u¯∗1 )2 dt ≤ B1 e2θ tf [|p2 − p̄2 |2 + |q2 − q̄2 |2 + |q3 − q̄3 |2 ]dt,
t0 t0
 tf  tf
(u∗2 − u¯∗2 )2 dt ≤ B2 e2θ tf [|p4 − p̄4 |2 + |q3 − q̄3 |2 + |q4 − q̄4 |2 ]dt,
t0 t0
 tf  tf
(u∗3 − u¯∗3 )2 dt ≤ B3 e2θ tf [|p3 − p̄3 |2 + |q3 − q̄3 |2 + |q5 − q̄5 |2 ]dt,
t0 t0

where B1 , B2 , and B3 are constants.

Therefore, we obtain
 tf
1
(p1 − p̄1 )2 (tf ) + θ |p1 − p̄1 |2 dt
2 t0
 tf  tf
≤ βεe−θ tf [|p1 − p̄1 |2 + |p2 − p̄2 |2 ]dt + βe−θ tf [|p1 − p̄1 |2
t0 t0
 tf
+ |p4 − p̄4 |2 ]dt + μ |p1 − p̄1 |2 dt,
t0

and
 tf  tf
1
(q1 − q̄1 )2 (tf ) + θ |q1 − q̄1 |2 dt ≤ βεe2θ tf [|p2 − p̄2 |2 + |q1 − q̄1 |2 ]dt
2 t0 t0
 JOURNAL OF BIOLOGICAL DYNAMICS 25

 tf  tf
2θ tf 2 2 2θ tf
+ βe [|p4 − p̄4 | + |q1 − q̄1 | ]dt + βεe [|p2 − p̄2 |2 + |q2 − q̄2 |2 ]dt
t0 t0
 tf  tf
2θ tf 2 2 θ tf
+ βe [|p4 − p̄4 | + |q2 − q̄2 | ]dt + μe [|p1 − p̄1 |2 + |q1 − q̄1 |2 ]dt.
t0 t0

Similarly, we derive the inequalities for p2 and p̄2 , p3 and p̄3 , p4 and p̄4 , p5 and p̄5 , p6 and
p̄6 , q2 and q̄2 , q3 and q̄3 , q4 and q̄4 , q5 and q̄5 , q6 and q̄6 . Adding all the inequalities, we
have
1
[(p1 − p̄1 )2 (tf ) + (p2 − p̄2 )2 (tf ) + (p3 − p̄3 )2 (tf )
2
+ (p4 − p̄4 )2 (tf ) + (p5 − p̄5 )2 (tf ) + (p6 − p̄6 )2 (tf )
+ (q1 − q̄1 )2 (t0 ) + (q2 − q̄2 )2 (t0 ) + (q3 − q̄3 )2 (t0 )
+ (q4 − q̄4 )2 (t0 ) + (q5 − q̄5 )2 (t0 ) + (q6 − q̄6 )2 (t0 )]
 tf
+θ [|p1 − p̄1 |2 + |p2 − p̄2 |2 + |p3 − p̄3 |2
t0

+ |p4 − p̄4 |2 + |p5 − p̄5 |2 + |p6 − p̄6 |2 + |q1 − q̄1 |2

+ |q2 − q̄2 |2 + |q3 − q̄3 |2 + |q4 − q̄4 |2 + |q5 − q̄5 |2 + |q6 − q̄6 |2 ]dt
 tf
3θ tf
≤ (K̃1 + K̃2 e ) [|p1 − p̄1 |2 + |p2 − p̄2 |2
t0

+ |p3 − p̄3 | + |p4 − p̄4 |2 + |p5 − p̄5 |2 + |p6 − p̄6 |2

2

+ |q1 − q̄1 |2 + |q2 − q̄2 |2 + |q3 − q̄3 |2 + |q4 − q̄4 |2 + |q5 − q̄5 |2 + |q6 − q̄6 |2 ]dt.

From the above equation, we have

 tf
3θ tf
(θ − K̃1 − K̃2 e ) [|p1 − p̄1 |2 + |p2 − p̄2 |2 + |p3 − p̄3 |2 + |p4 − p̄4 |2 + |p5 − p̄5 |2
t0

+ |p6 − p̄6 |2 + |q1 − q̄1 |2 + |q2 − q̄2 |2 + |q3 − q̄3 |2 + |q4 − q̄4 |2
+ |q5 − q̄5 |2 + |q6 − q̄6 |2 ]dt ≤ 0,

where K̃1 and K̃2 depend on the coefficients and the bounds on pi and qi , i = 1, 2 . . . , 6.
We choose θ such that θ > K̃1 + K̃2 and tf < 3θ1 ln( θ − K̃1
K̃2
), then p1 = p̄1 , p2 = p̄2 ,
p3 = p̄3 , p4 = p̄4 , p5 = p̄5 , p6 = p̄6 , q1 = q̄1 , q2 = q̄2 , q3 = q̄3 , q4 = q̄4 , q5 = q̄5 , q6 = q̄6 .
Therefore, Model (6) has a unique optimal solution within a small time interval. 

3.2. Numerical simulations

In order to illustrate the feasibility of the theoretical results and the control strategies,
numerical simulations are carried out to study the influence of the optimal control strategy
on the transmission of HIV.
26 L. XUE ET AL.

Figure 11. The number of infected individuals when u1 = 0, u2 = 0, and u3 = 0.

The weights of state variables and control variables in the Hamiltonian function are set
as m1 = 20, m2 = 30, m3 = 30, n1 = 45, n2 = 25, and n3 = 10. Based on the three control
variables, u1 (t), u2 (t), and u3 (t), we propose the following four control strategies.
To compare the control effect after implementing the control strategies, we first simulate
the number of infected individuals without control as shown in Figure 11. The infected
individuals include latent, aware, and unaware infected individuals. Figure 11 shows that
the number of infected individuals increases from 2002 to 2014, then decreases from 2015
to 2030. By the end of 2030, the number of infected individuals is 45905000. Next, we
explore the impact of control strategies on HIV transmission.
Strategy 1: A combination of screening for latent individuals u1 (t) and education for
unaware infected individuals u2 (t) is applied. In other words, u1 = 0, u2 = 0, and u3 = 0.
Then, we optimize the function J in Equation (8).
Figure 12(a) shows the effects of control strategies u1 and u2 over time. Controls u1 and
u2 maintain their maximum values for the first four months and five months, respectively.
Then, u1 remains constant at the value of 0.95 until 2009. From 2010, control u1 begins to
decrease slowly. From May 2002 to January 2030, the control u2 remains constant at the
value of 0.95, then slowly decreases to zero. Figure 12(b) shows the effect of controls u1
and u2 on the number of infected individuals. Comparing with the case without control
strategies (see Figure 11), implementing controls u1 and u2 can significantly reduce the
number of infected individuals. In particular, HIV can be eradicated in 2003.
Strategy 2: A combination of screening for latent individuals u1 (t) and treatments for
aware infected individuals u3 (t) is considered. In other words, u1 = 0, u3 = 0, and u2 = 0.
Then, we optimize the cost function J in Equation (8) to analyse the control effects.
Figure 13(a) shows the effects of controls u1 and u3 over time. As shown in the figure,
controls u1 and u3 are at the maximum control level of 100% for 37 months, then these
control measures gradually decrease until reaching 95%. Eventually, the controls u1 and u3
decrease to zero. Figure 13(b) illustrates the effect of controls u1 and u3 on the number of
infected individuals. Compared with the case without control strategies, applying controls
 JOURNAL OF BIOLOGICAL DYNAMICS 27

Figure 12. The impacts of implementing control Strategies 1. (a) The optimal control solutions u1 and
u2 . (b) The size of E, I1 , and I2 under the controls of u1 and u2 .

Figure 13. The impacts of implementing control Strategies 2. (a) The optimal control solutions u1 and
u3 . (b) The total size of E, I1 , and I2 under the controls of u1 and u3 .

u1 and u3 could reduce the total number of latent, aware, and unaware infected individuals.
In addition, we find that the combined use of controls u1 and u3 could eradicate HIV in
2020. Therefore, optimal control effects can be achieved by screening latent infection indi-
viduals and treating the infected individuals during a long period. Then, we can control
the spread of HIV by improving the awareness and increasing the opportunities of being
treated.
Strategy 3: A combination of education for infected individuals u2 (t) and treatment
for aware infected individuals u3 (t) is considered. In other words, u1 = 0, u2 = 0, and
u3 = 0. Then, we optimize the cost function J in Equation (8) to analyse the control effect
as follows.
28 L. XUE ET AL.

Figure 14. The impacts of implementing control Strategies 3. (a) The optimal control solutions u2 and
u3 . (b) The total size of E, I1 , and I2 under the controls of u2 and u3 .

Figure 14(a) shows the effects of control strategies u2 and u3 . At the early stage, the
controls u2 and u3 are at the maximum control level of 100% for 19 months and 23 months,
respectively. Then, the two control strategies keep at 95%, and eventually decrease to zero.
Figure 14(b) indicates the effect of controls u2 and u3 on the number of infected individuals.
The results show that under the controls u2 and u3 , the total numbers of latent, aware, and
unaware infected individuals greatly decrease compared with the case without control (see
Figure 11). Moreover, we find that HIV is eradicated in 2005 when the controls u2 and
u3 are implemented. This indicates that these controls are very effective to mitigate HIV
transmission.
Strategy 4: A combination of screening u1 (t), education for aware infected individuals
u2 (t) and treatment for aware infected individuals u3 (t) is considered. In other words, u1 =
0, u2 = 0, u3 = 0. Then, we optimize the cost function J in Equation (8) to analyse the
control effect.
Figure 15 indicates the change of the number of infected individuals when three controls
are implemented together. In Figure 15(a), the controls u1 , u2 , and u3 achieve the maxi-
mum control level of 100% and last for about four, five, and seven months, respectively.
Then, control u1 decreases to 95% level until 2011 and slowly decreases to zero in 2030.
For control u2 , it has maintained a 95% control level from August 2002 to February 2029,
then slowly reduces to zero. However, the control strength of control u3 first decreases and
increases from August 2002 to May 2005. Then, control u3 slowly reduces to zero in 2030.
Figure 15(b) shows the effect of controls u1 , u2 , and u3 on the number of infected individu-
als. The results show that compared with the case without control strategies (see Figure 11),
controls u1 , u2 , and u3 can reduce the total numbers of latent, aware, and unaware infected
individuals. It means that under the control strategies, more infected individuals receive
treatments, and more latent and unaware infected individuals become aware.
Further, we compare the impact of four control strategies on the number of infected
individuals, that is, latent, aware, and unaware infected individuals as shown in Figure 16.
We find that Strategy 4: u1 = 0, u2 = 0, u3 = 0 is the most efficient. This is because Strategy
 JOURNAL OF BIOLOGICAL DYNAMICS 29

Figure 15. The impacts of implementing control Strategies 4. (a) The optimal control solutions u1 , u2 ,
and u3 . (b) The total size of E, I1 , and I2 under the control of u1 , u2 , and u3 .

Figure 16. The impact of different control strategies on the number of infected individuals.

4 can eradicate HIV in the shortest time (about 1.5 years). Other strategies need take more
time to achieve the same control effect. To judge whether the four control strategies can
achieve the three goals of 90% reduction and eradicate AIDS by 2030 proposed by the
UNAIDS, we summarize the control results in Table 4. Table 4 indicates that four control
strategies can achieve the control objectives proposed by the UNAIDS.
Next, we study the influence of control weights on Strategy 4. We compare the opti-
mal control curves and the numbers of infected individuals with n1 = 50, n1 = 100, and
n1 = 150 when n2 = 25 and n3 = 10. In Figure 17, with the increase of n1 , the duration of
the maximum control level of u1 becomes shorter, while the duration of the maximum con-
trol levels of u2 and u3 becomes longer. When n1 = 50, the controls u1 , u2 , and u3 reach
30 L. XUE ET AL.

Figure 17. Impact of changes on the cost weight of control u1 (t), n1 , on control strategies and the num-
ber of infected individuals. (a) Weight: n1 = 50, n2 = 25, n3 = 75. (b) Weight: n1 = 100, n2 = 25, n3 =
10. (c) Weight: n1 = 150, n2 = 25, n3 = 10. (d) The number of infected individuals under different cost
weights of n1 .

the 100% control level at the early stage and last for about four, five, and seven months,
respectively, then the control levels reduce to 95% as shown in Figure 17(a). The control
u1 starts to slowly decrease to zero from 2011. The control level of control u2 remains at
95% level from June 2002 to March 2030, then the control level gradually decreases to zero.
The control u3 first decreases, then increases from August 2002 to May 2005. Then, con-
trol u3 slowly reduces to zero in 2030. In Figure 17(b), when n1 = 100, the controls u1 ,
u2 , and u3 reach the 100% control level at the early stage and last for about three, five,
and seven months, respectively. Then, the controls u1 , u2 , and u3 maintain 95% control
level until 2008, 2030, and 2009, respectively, after which they slowly decrease to zero. In
Figure 17(c), when n1 = 150, the controls u1 , u2 , and u3 reach the 100% control level and
last for about three, five, and seven months, respectively. Then, the controls u1 , u2 , and u3
maintain 95% control level until 2008, 2030, and 2009, respectively, after which they slowly
decrease to zero. In addition, we explore the effect of different n1 values on the number of
infected individuals. Figure 17(d) shows that the smaller the weight n1 , the earlier the HIV
eradication can be achieved.
 JOURNAL OF BIOLOGICAL DYNAMICS 31

Figure 18. Impact of changes on the cost weight of control u2 (t), n2 , on control strategies and the num-
ber of infected individuals. (a) Weight: n1 = 45, n2 = 20, n3 = 10. (b) Weight: n1 = 45, n2 = 100, n3 =
10. (c) Weight: n1 = 45, n2 = 180, n3 = 10. (d) The number of infected individuals under different cost
weights of n2 .

The effect of weight n2 on the control curves and the number of infected individuals with
n2 = 20, n2 = 100, and n2 = 180 is shown in Figure 18. With the increase of the weight
n2 , the maximum control level of control u2 decreases gradually. In Figure 18(a), when
n2 = 20, the controls u1 , u2 , and u3 reach the 100% control level and last for about four,
five, and seven months, respectively. After the maximum control level, the control u1 starts
to decrease slowly after eight years of implementing the control level of 95%, the control
u2 maintains a control level of 95% all the time, while the control u3 first decreases in July
2002 and increases in August 2002, then gradually decrease after June 2004. In Figure 18(b),
when n2 = 100, the controls u1 , u2 , and u3 reach the 100% control level at the early stage
and last for about four, three, and seven months, respectively. Then, the controls u1 , u2 ,
and u3 maintain 95% control level until 2024, 2016, and 2013, respectively, after which
they slowly decrease to zero. In Figure 18(c), when n2 = 180, the controls u1 , u2 , and u3
reach the 100% control level and last for about four, two, and seven months, respectively.
Then, the controls u1 , u2 , and u3 maintain 95% control level until 2029, 2015, and 2022,
respectively, after which they slowly decrease to zero. Moreover, we explore the effect of
different values of n2 on the number of infected individuals. Figure 18(d) illustrates that
the smaller the weight n2 , the better control effect.
32 L. XUE ET AL.

Figure 19. Impact of changes on the cost weight of control u3 (t), n3 , on control strategies and the num-
ber of infected individuals. (a) Weight: n1 = 45, n2 = 20, n3 = 4. (b) Weight: n1 = 45, n2 = 20, n3 =
8. (c) Weight: n1 = 45, n2 = 20, n3 = 12. (d) The number of infected individuals under different cost
weights of n3 .

In addition, we explored the effect of different values of n3 on the control strategies and
the number of infected individuals. Here, we explore the cases of n3 = 4, n3 = 8, and n3 =
12, respectively. Figure 19 shows that with the increase of the weight n3 , the maximum
control level of control strategy u3 decreases gradually. In Figure 19(a), when n3 = 4, the
controls u1 , u2 , and u3 reach the 100% control level at the early stage and last for about
four, five, and eight months, respectively. Then, the controls u1 , u2 , and u3 maintain 95%
control level until 2010, 2029, and 2014, respectively, after which they slowly decrease to
zero. Figure 19(b) shows that when n3 = 8, the controls u1 , u2 , and u3 reach the 100%
control level at the early stage and last for about four, five, and seven months, respectively.
Then, the controls u1 and u2 maintain 95% control level until 2010 and 2029, respectively,
after which they slowly decrease to zero. For control u3 , it decreases from the maximum
control level to 70.7%, then starts to gradually increase to 95% in October 2002. After 43
months, control u3 begins to decrease. Figure 19(c) shows that when n3 = 12, the controls
u1 , u2 , and u3 reach the 100% control level and last for about four, five, and seven months,
respectively. Then, the controls u1 and u2 maintain 95% control level until 2011 and 2029,
respectively, after which they slowly decrease to zero. After the maximum control level,
the control u1 starts to decrease slowly after nine years of implementing the control level
of 95%, the control u2 maintains the control level of 95% all the time, while the control
 JOURNAL OF BIOLOGICAL DYNAMICS 33

Table 3. Indices for the effectivenesses of control strategies.

 tf
Strategies = 0 E(t) + I1 (t) + I2 (t)dt  = (1 − c
s
) × 100%
No control 45,905,000 0
Strategy 1 3,553,479 92.26%
Strategy 2 7,167,623 84.39%
Strategy 3 7,041,835 84.66%
Strategy 4 1,902,933 95.85%

u3 first decreases in July 2002 and increases in September 2003, then gradually decreases
after November 2005. At last, we explore the effect of different n3 values on the number of
infected individuals as shown in Figure 19(d). We find that the smaller the weight n3 , the
better control effect.
In summary, as the weight n1 increases, the control level of u1 gradually decreases. At
the same time, the control levels of u2 and u3 also decrease. As the weight n2 increases, the
control level of u2 gradually decreases, and the control levels of u1 and u3 decrease. As the
weight n3 increases, the control level of u3 gradually decreases, and the control levels of u1
and u2 decrease.

3.3. Efficiency analysis and cost-effectiveness analysis

Although all four control strategies can achieve the control objectives proposed by the
UNAIDS, we also need to consider the corresponding efficiency and costs. Therefore, we
explore the efficiency and cost-effectiveness of four control strategies in this section.
First, we perform the efficacy analysis using the method in references [12,27,47]. The
efficiency index is defined as

c
 = 1− × 100%,
s

where c is the cumulative number of infected individuals when different control strategies
are implemented and s is the cumulative number of infected individuals in absence of any
control strategies. The cumulative number of infected individuals during the time interval
[0, tf ] is denoted by
 tf
= [E(t) + I1 (t) + I2 (t)]dt,
0
where tf indicates the end time of the implementation controls. In this subsection, tf equals
to 29 years.
The best strategy has the biggest efficiency index [1,5]. It can be seen from Table 3 that
the effective indexes of four control strategies. The effective indexes show that Strategies 1,
2, 3, and 4 are effective to mitigate HIV transmission, but the most effective control strategy
is Strategy 4. Next, we explore the costs of four control strategies.
 tf
The total costs is Costs = 0 [ n21 u21 (t) + n22 u22 (t) + n23 u23 (t)]dt, where n1 = 45, n2 = 25,
n3 = 10, and tf = 29. The total costs of different control strategies as shown in Table 4.
The result shows that Strategy 1 is the most cost-effective. However, the most expensive
strategy is Strategy 3, since its cost is 4.3 times as that of Strategy 1. This may be because the
control of screening latent individuals is not included in Strategy 3, it takes a long time to
34 L. XUE ET AL.

Table 4. Comparison of impacts of four strategies by 2020.

Strategies Total infectious individuals Total infectious averted Total costs Incidence reduction
No control 45,905,000 – – –
Strategy 1 3,553,479 42,351,521 8408 92.26%
Strategy 2 7,167,623 38,737,377 14,351 84.39%
Strategy 3 7,041,835 38,863,165 36,270 84.66%
Strategy 4 1,902,933 44,002,067 19,735 95.85%

implement the control to achieve the control goal. Since the strategies that include control
of screening latent individuals can end the epidemic in a relatively short time, the cost is
relatively low.

4. Discussion and conclusion

This work analyses the spread of HIV via a mathematical model incorporating susceptible
individuals, latent individuals, unaware infected individuals, aware infected individuals,
infected individuals receiving ART treatment, and AIDS individuals. Based on the model,
we carry out theoretical analysis and numerical simulations. The theoretical analysis shows
that when R0 < 1, the disease free equilibrium is globally asymptotically stable, and the dis-
ease gradually dies out. When R0 > 1, the endemic equilibrium is globally asymptotically
stable, and the disease spreads. We obtain the parameter values by the MCMC method.
Through numerical simulations, we verify the stability of the disease free equilibrium and
the endemic equilibrium. We further analyse the effects of a single measure and multiple
measures on disease transmission. Compared with a single measure, multiple measures
can control the transmission of disease more effectively.
We incorporate mitigation strategies, including treating aware infected individuals,
screening latent individuals, and educating unaware individuals into the model. We apply
Pontryagin’s Maximum Principle to derive optimal control strategies. The results show that
the optimal control strategy is the combination of all three control measures. Since people
who receive ART treatments and aware infected individuals are not likely to transmit the
infection, the epidemic can be brought under control when more infected individuals are
aware of their infection and more people receive ART treatments. When all three control
measures are implemented, AIDS can be end in the shortest time. In our study, we find
that each of the four different control strategies in this work can achieve the three 90%
reduction goals and end the AIDS epidemic by 2030 proposed by the UNAIDS in 2014.
Simultaneously, the earlier the control strategies are implemented, the sooner AIDS can
be eradicated. Particularly, we find that the proportion of aware infected individuals has
an important influence on the transmission of HIV. The greater the proportion of humans
who are aware infected, the easier it is to control the spread of HIV. This is because ART
therapy can achieve a great reduction in HIV incidence, while more efficient HIV testing
is needed [37].
Finally, we analyse the impact of cost changes according to the optimal control strat-
egy. The results show that the number of infected individuals can be greatly reduced
when the cost of implementing all control strategies is lower. When more medicines for
HIV are covered by medical insurances, more infected individuals can receive treatments
[29]. Moreover, we analyse the total costs of control strategies and find that the most
 JOURNAL OF BIOLOGICAL DYNAMICS 35

cost-effective strategy is a combination of enhanced screening for latent individuals and

education for unaware infected. The reason is that the combined implementation of these
two control strategies can avoid more infected individuals, which in turn can save the costs
for testing and treatment [37]. Therefore, we can mitigate the spread of AIDS by improving
medical technology, increasing testing rates, and intensify education for unaware infected
individuals.
The duration of AIDS is long, and it is difficult to obtain the number of infected indi-
viduals at each stage. Once such data are available, we can evaluate whether the goal of
eradicating AIDS can be achieved by 2030 more accurately. Moreover, the model can
be applied to study many other diseases with similar transmission mechanisms, such as
COVID-19, Syphilis, and hepatitis B. We did not take into account detection rate and
the effect of HIV co-infection with other diseases on HIV transmission in this work. In
future work, we will study the effects of the detection rate and the co-infection of HIV with
other diseases, and discuss whether the eradication of AIDS can be achieved earlier once
an effective vaccine is available.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Funding
LX is funded by the National Natural Science Foundation of China [grant number 12171116]
and Fundamental Research Funds for the Central Universities of China [grant numbers
3072020CFT2402 and 3072022TS2404]. WS is funded by the Fundamental Research Funds for the
Central Universities of China [grant number 3072021CFP2401].

References
[1] H. Abboubakar, J.C. Kamgang, L.N. Nkamba, and D. Tieudjo, Bifurcation thresholds and opti-
mal control in transmission dynamics of arboviral diseases, J. Math. Biol. 76(1–2) (2018), pp.
379–427.
[2] T. Bastys, V. Gapsys, N.T. Doncheva, R. Kaiser, B.L. Groot, and O.V. Kalinina, Consistent predic-
tion of mutation effect on drug binding in HIV-1 protease using alchemical calculations, J. Chem.
Theory. Comput. 14(7) (2018), pp. 3397–3408.
[3] J.E. Bennett, R. Dolin, and M.J. Blaser, Principles and practice of infectious diseases, Elsevier
Health Sci. 8(5) (2010), pp. 326.
[4] L. Cai, X. Li, M. Ghosh, and B. Guo, Stability analysis of an HIV/AIDS epidemic model with
treatment, J. Comput. Appl. Math. 229(1) (2009), pp. 313–323.
[5] S.A. Carvalho, S.O.D. Silva, and I.D.C. Charret, Mathematical modeling of dengue epidemic:
Control methods and vaccination strategies, Theory Biosci. 138(2) (2019), pp. 223–239.
[6] A.N. Chatterjee and P.K. Roy, Antiviral drug treatment along with immune activator IL-2:
A control-based mathematical approach for HIV infection, Int. J. Control 85(2) (2012), pp.
220–237.
[7] Chinese Center for Disease Control and Prevention, Bureau of disease control and prevention,
available at http://www.nhc.gov.cn/jkj/s2907/new_list.shtml?tdsourcetag = s_pcqq_aiomsg.
Accessed 13 December 2022.
[8] N. Chitnis, J.M. Cushing, and J.M. Hyman, Bifurcation analysis of a mathematical model for
Malaria transmission, SIAM. J. Appl. Math. 67(1) (2006), pp. 24–45.
[9] R. Denysiuk, C.J. Silva, and D.F.M. Torres, Multiobjective approach to optimal control for a
tuberculosis model, Optim. Methods Softw. 30(4) (2015), pp. 893–910.
36 L. XUE ET AL.

[10] P. Dreessche and J. Watmough, Reproduction numbers and sub-threshold endemic equilibria for
compartmental models of disease transmission, Math. Biosci. 180(1–2) (2002), pp. 29–48.
[11] B. Dubey, P. Dubey, and U.S. Dubey, Dynamics of an SIR model with nonlinear incidence and
treatment rate, Appl. Appl. Math. Int. J. 10(2) (2015), pp. 718–737.
[12] S. Ghosh, A.N. Chatterjee, P.K. Roy, N. Grigorenko, E. Khailov, and E. Grigorieva, Mathemat-
ical modeling and control of the cell dynamics in Leprosy, Comput. Math. Model. 32 (2021), pp.
52–74.
[13] M.S. Gottlieb, H.M. Schanker, P.T. Fan, A. Saxon, J.D. Weisman, and I. Pozalski, Pneumocystis
pneumonia-losangeles, MMWR Morb. Mortal. Wkly. Rep. 30(21) (1981), pp. 250–252.
[14] R.M. Granich, C.F. Gilks, C. Dye, K.M.D. Cock, and B.G. Williams, Universal voluntary hiv
testing with immediate antiretroviral therapy as a strategy for elimination of hiv transmission: A
mathematical model, The Lancet 373 (2009), pp. 48–57.
[15] S. Hota, F. Agusto, H.R. Joshi, and S. Lenhart, Optimal control and stability analysis of and
epidemic model with education campaign and treatment, Dyn. Syst. Differ. Equ. Appl. AIMS
Proc. 2015 (2015), pp. 621–634.
[16] S.D. Hove-Musekwa and F. Nyabadza, The dynamics of an HIV/AIDS model with screened
disease carriers, Comput. Math. Methods Med. 10(4) (2015), pp. 287–305.
[17] J. M. Hyman and E.Ann Stanley, Using mathematical models to understand the AIDS epidemic,
Math. Biosci. 90(1–2) (1988), pp. 415–473.
[18] H.R. Joshi, Optimal control of an HIV immunology model, Optim. Control Appl. Methods 23
(2002), pp. 199–213.
[19] H.R. Joshi, S. Lenhart, S. Hota, and F. Agusto, Optimal control of an SIR model with changing
behavior through an education campaign, Electron. J. Differ. Equ. 2015(50) (2015), pp. 1–14.
[20] J.P. LaSalle, The Stability of Dynamical Systems, SIAM, Philadephia, 1976.
[21] S. Lenhart and J.T. Workman, Optimal Control Applied to Biological Models, Chapman and Hall,
London, 2007.
[22] J. Li, Y. Yang, and Y. Zhou, Global stability of an epidemic model with latent stage and vaccination,
Nonlinear Anal. Real World Appl. 12(4) (2011), pp. 2163–2173.
[23] R. Liu, J. Wu, and H. Zhu, Media/psychological impact on multiple outbreaks of emerging
infectious diseases, Comput. Math. Methods Med. 8(3) (2007), pp. 153–164.
[24] J. Lou, J. Cheng, Y. Li, C. Zhang, H. Xing, Y. Ruan, and Y. Shao, Comparison of different strategies
for controlling HIV/AIDS spreading in MSM, Infect. Dis. Model. 3 (2018), pp. 293–300.
[25] M. Marsudi, N. Hidayat, and R.B.E. Wibowo, Application of optimal control strategies for the
spread of HIV in a population, Res. J. Life Sci. 4(1) (2017), pp. 1–9.
[26] N.H. Marsudi and R.B.E. Wibowo, Optimal control and sensitivity analysis of HIV model with
public health education campaign and antiretroviral therapy, AIP Conf. Proc. 2021 (2018),
Article ID 060033.
[27] J. Mondal, P. Samui, and A.N. Chatterjee, Effect of SOF/VEL antiviral therapy for HCV
treatment, Lett. Biomath. 8(1) (2021), pp. 191–213.
[28] Z. Mukandavire, W. Garira, and J.M. Tchuenche, Modelling effects of public health educa-
tional campaigns on HIV/AIDS transmission dynamics, Appl. Math. Model. 33(4) (2009), pp.
2084–2095.
[29] National Healthcare Security Administration, Notice of the general office of the state coun-
cil on printing and distributing the ’14th five-year’ national medical security plan, available at
https://www.nhsa.gov.cn/art/2021/9/29/art_37_6137.html, Accessed 29 September 2021.
[30] F. Nyabadza, Z. Mukandavire, and S.D. Hove-Musekwa, Modelling the HIV/AIDS epidemic
trends in South Africa: Insights from a simple mathematical model, Nonlinear Anal. Real World
Appl. 12(4) (2011), pp. 2091–2104.
[31] L.S. Pontryagin, The mathematical theory of optimal processes and differential games, J. Oper.
Res. Soc. 16(4) (1985), pp. 493–494.
[32] A. Rachah and D.F.M. Torres, Mathematical modelling, simulation, and optimal control of the
2014 Ebola outbreak in West Africa, Discrete Dyn. Nat. Soc. 2015 (2015), pp. 1–9.
[33] H.S. Rodrigues, M.T.T. Monteiro, and D.F.M. Torres, Vaccination models and optimal control
strategies to dengue, Math. Biosci. 247(1) (2014), pp. 1–12.
 JOURNAL OF BIOLOGICAL DYNAMICS 37

[34] P.K. Roy, S. Chowdhury, A.N. Chatterjee, J. Chattopadhyay, and R. Norman, A mathematical
model on CTL mediated control of HIV infection in a long term drug therapy, J. Biol. Syst. 21(3)
(2013), pp. 7–9.
[35] P.K. Roy, S. Saha, and F.A. Basir, Effect of awareness programs in controlling the disease
HIV/AIDS: An optimal control theoretic approach, Adv. Differ. Equ. 2015(1) (2015), pp. 1–18.
[36] A.K. Roy, M. Nelson, and P.K Roy, A control-based mathematical study on psoriasis dynam-
ics with special emphasis on IL-21 and IFN-γ interaction network, Math. Methods Appl. Sci. 7
(2021), pp. 1–18.
[37] H.V. Rooyen, R.V. Barnabas, J.M. Baeten, Z. Phakathi, P. Joseph, M. Krows, T. Hong, P.M. Mur-
nane, P.M. Murnane, and C. Celum, High HIV testing uptake and linkage to care in a novel
program of home-based HIV counseling and testing with facilitated referral in Kwazulu-natal,
south Africa, J. Acquir. Immune Defic. Syndr. 64(1) (2013), pp. e1–e8.
[38] X. Rui, Global stability of an HIV-1 infection model with saturation infection and intracellular
delay, J. Math. Anal. Appl. 375(1) (2011), pp. 75–81.
[39] R. Safiel, E.S. Massawe, and O.D. Makinde, Modelling the effect screening and treatment on trans-
mission of HIV/AIDS infection in a population american, Am. J. Math. Stat. 2(4) (2012), pp.
75–88.
[40] Z. Shuai and P. Van den driessche, Global stability of infectious disease models using lyapunov
functions, SIAM J. Appl. Math. 73(4) (2013), pp. 1513–1532.
[41] C.J. Silva and D. Torres, Global stability for a HIV/AIDS model, Commun. Fac. Sci. Univ. Ank.
Ser.67(1) (2017), pp. 93–101.
[42] X. Song and A.U. Neumann, Global stability and periodic solution of the viral dynamics, J. Math.
Anal. Appl. 329(1) (2007), pp. 281–297.
[43] X. Song, X. Zhou, and X. Zhao, Properties of stability and hopf bifurcation for a HIV infection
model with time delay, Appl. Math. Model. 34(1) (2010), pp. 1511–1523.
[44] A. Suryanto and I. Darti, Optimal control of an HIV model with changing behavior through an
education campaign, screening and treatment, IOP Conf. Ser. Mater. Sci. Eng. 546 (2019), Article
ID 052043.
[45] A. Tripathi, R. Naresh, and D. Sharma, Modelling the effect of screening of unaware infectives on
the spread of HIV infection, Appl. Math. Comput. 184(2) (2007), pp. 1053–1068.
[46] K. Wang, W. Wang, H. Pang, and X. Liu, Complex dynamic behavior in a viral model with delayed
immune response, Physica D 226(2) (2007), pp. 197–208.
[47] B. Wang, J. Mondal, P. Samui, A.N. Chatterjee, and A. Yusuf, Effect of an antiviral drug control
and its variable order fractional network in host COVID-19 kinetics, Eur. Phys. J. Spec. Top. 231
(2022), pp. 1–15.
[48] T. Zhang, M. Jia, H. Luo, Y. Zhou, and N. Wang, Study on a HIV/AIDS model with application
to Yunnan province, China, Appl. Math. Model. 35(9) (2011), pp. 4379–4392.