The factors associated with natural disease progression from HIV to AIDS in the absence of ART, a propensity score matching analysis
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Epidemiology and Infection The factors associated with natural disease
cambridge.org/hyg
progression from HIV to AIDS in the absence of
ART, a propensity score matching analysis
X. C. Jia1,2, Z. H. Xia3, N. Shi4, Y. P. Wang1, Z. X. Luo1, Y. L. Yang1 and X. Z. Shi1
Original Paper
1
Cite this article: Jia XC, Xia ZH, Shi N, Wang Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou
YP, Luo ZX, Yang YL, Shi XZ (2020). The factors 450001, China; 2Zhengzhou University Library, Zhengzhou University, Zhengzhou 450001, China; 3Department of
associated with natural disease progression Hospital Infection Control, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China and
4
from HIV to AIDS in the absence of ART, a Department of Physical Diagnosis, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001,
propensity score matching analysis. China
Epidemiology and Infection 148, e57, 1–7.
https://doi.org/10.1017/S0950268820000540
Abstract
Received: 17 November 2019 This study aimed at comparing the factors associated with the natural progression between
Revised: 21 December 2019
Accepted: 14 January 2020
typical progressors (TPs) and rapid progressors (RPs) in HIV-infected individuals. A retro-
spective study was conducted on 2095 eligible HIV-infected individuals from 1995 to 2016
Key words: in a high-risk area of Henan Province, China. Propensity score matching was used to balance
AIDS; propensity score matching; rapid covariates, and the conditional logistic regression analyses were performed to explore the fac-
progressors; typical progressors
tors of natural disease progression among HIV infectors. A total of 379 pairs of RPs and TPs
Authors for correspondence: Y. L. Yang, were matched. The standardised difference values of all covariates were less than 10%. HIV-
E-mail: ylyang377@126.com; infected individuals transmitted through sexual transmission (odds ratio (OR) 0.56, 95% con-
X. Z. Shi, E-mail: xzshi@zzu.edu.cn fidence interval (CI) 0.36–0.85) were more likely to progress to AIDS compared with those
infected through contaminated blood. Older age at diagnosis of HIV-infected individuals
(OR 0.72, 95% CI 0.58–0.89) exhibited a faster progression to AIDS. HIV-infected individuals
identified through a unique survey (OR 7.01, 95% CI 2.99–16.44) were less likely to progress
to AIDS compared with those identified through medical institutions. HIV-infected indivi-
duals who had higher baseline CD4+T cell counts (OR 3.37, 95% CI 2.59–4.38) had a slower
progression to AIDS. These findings provide evidence for natural disease progression from
HIV to AIDS between TPs and RPs.
Introduction
Acquired immune deficiency syndrome (AIDS) is a chronic, potentially fatal spectrum of dis-
eases caused by the human immunodeficiency virus (HIV) and continues to be a serious public
health challenge worldwide. Since the beginning of the epidemic, 32.0 million people have died
of AIDS-related illnesses and an estimated 37.9 million people globally are living with HIV at
the end of 2018 [1]. According to the Chinese Center for Disease Control and Prevention
(CDC), 262 442 people have died from AIDS-related illnesses from 1985 to the end of
October 2018. There were approximately 849 602 people living with HIV/AIDS at the end of
October 2018 in China. The prevention and control of HIV/AIDS still face a daunting challenge.
Nearly all the HIV-infected individuals exhibit a progressive depletion of CD4+T
lymphocytes and imbalance in CD4+T-cell homoeostasis, the hall mark of HIV infection.
HIV infections appear immunodeficiency, a manifestation of clinical symptoms, and inevitable
progression to AIDS eventually. Accumulating evidence indicated that the increase of HIV
plasma viral load, decrease of CD4+ lymphocyte counts and concomitant comorbidities were
associated with disparities in survival whether receiving antiretroviral therapy (ART) or not
© The Author(s), 2020. Published by [2–4]. With the widespread use of ART, new HIV infections have declined by an estimated
Cambridge University Press. This is an Open 16% and AIDS-related mortality has declined by 33% since 2010 [1]. However, the number
Access article, distributed under the terms of
the Creative Commons Attribution-
of deaths due to HIV/AIDS was still high worldwide in 2018 [1]. These findings emphasise
NonCommercial-ShareAlike licence (http:// the need to investigate major determinants of HIV/AIDS survival, even though the natural
creativecommons.org/licenses/by-nc-sa/4.0/), disease progression of HIV infection remains elusive. Hence, it becomes extremely essential
which permits non-commercial re-use, and challenging to address and explore the significant factors associated with natural course
distribution, and reproduction in any medium,
and progression to immunodeficiency among HIV infections who have not received ART.
provided the same Creative Commons licence
is included and the original work is properly According to the duration from HIV to AIDS, disease progression is categorised into rapid,
cited. The written permission of Cambridge typical and long-term non-progression in the absence of ART [5, 6]. Typical progressors (TPs)
University Press must be obtained for have a typical depletion of CD4+T cells and high HIV-RNA, and progression to AIDS occurs
commercial re-use. within 5–10 years of acquiring HIV. And rapid progressors (RPs) have CD4+T cell counts below
200 cells/mm3 or develop AIDS-related illnesses within 3–5 years after HIV infection [7, 8].
However, the long-term non-progressors (LTNPs), a very small percentage of HIV-infected
individuals (1–5%) remain asymptomatic, with a durable maintenance of CD4+T cell counts
⩾500 cells/mm3, low levels of viral replication and can remain healthy without significant
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 18 Oct 2021 at 14:31:23, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S09502688200005402 X. C. Jia et al.
progression for more than 10 years without ART [9]. Most of the deviation of propensity score [13]. Moreover, the absolute stan-
previous studies primarily focused on the differences of disease dardised difference was selected to examine the balance of all
progression between LTNPs and TPs/RPs [5, 8]. However, the fac- measured covariates, because it is more appropriate to assess bal-
tors associated with TPs and RPs remain uninvestigated [10, 11]. ance in observational studies compared with the significance test
There might be some differences of natural disease progression [13–15]. After matching, all the absolute standardised differences
between TPs and RPs among some factors. were below 10% for all covariates indicated that these covariates
Propensity score matching (PSM) was proposed by exhibit no imbalances among RPs and TPs.
Rosenbaum and Rubin [12] in 1983, as a tool to estimate and
reduce the causal effects of measured confounding factors in
observational studies. PSM has been widely applied in medical Statistical analysis
research, especially when a randomised controlled clinical trial Continuous variables were presented as mean (±S.D.), and categor-
is difficult to perform. In this study, we aimed at investigating ical variables were presented as number (%). For descriptive
the differences between TPs and RPs among HIV-infected indivi- analysis, a comparison of covariates and explanatory variables
duals to identify the factors associated with the natural progres- between the two groups (RPs vs. TPs) was performed using the
sion of HIV infection after adjusting for potential confounders χ 2 test or Wilcoxon rank sum test before matching. The post-
by using PSM. match comparison was performed using the McNemar test or
paired Wilcoxon-signed rank sum test. For the propensity score-
matched samples, conditional logistic regression analyses were fit-
Methods
ted to estimate the association between potential factors and the
Study subjects natural disease progression of HIV infection. The report of abso-
lute standardised differences was generated using R version 3.5.0
There were 13 142 HIV/AIDS patients in a high-risk area of
(R Foundation for Statistical Computing, Vienna, Austria, https://
Henan Province between 1995 and 2016. A retrospective study
www.R-project.org/). All statistical analyses were conducted using
was conducted to assess the natural disease progression from
SPSS 22.0 software (IBM, Crop, Armonk, NY, USA). A P-value
HIV to AIDS among HIV-infected individuals in the absence of
less than 0.05 was considered statistically significant.
ART. HIV-positive status of all subjects was confirmed by testing
positive for HIV using enzyme-linked immunosorbent assay and
western blot analysis. HIV-infected individuals and AIDS patients Results
were followed-up every 6 and 3 months, respectively. Seropositive
individuals who had not received ART were selected. Those sub- Patient characteristics
jects aged less than 15 years at diagnosis were excluded from the A total of 2095 HIV-infected individuals (TPs: n = 379, RPs: n =
study, as diagnostic criteria and clinical stage are inconsistent 1716) meeting the eligibility criteria were included. The mean age
among patients less than 15 years and over 15 years. of TPs was 38.1 (±10.1) years; the mean age of RPs was 40.5
(±9.8) years. All 379 TP HIV-infected individuals were success-
fully matched. Before matching, the results of covariates compari-
Measurements and definition
son between the two groups are shown in Table 1. After matching,
The socio-demographic information including age at diagnosis, absolute standardised differences for all measured covariates were
gender, census register, marital status, nationality, occupation, below 10% indicating that these measured covariates were well
education level, disease status (HIV or AIDS), contact with balanced between TPs and RPs (Fig. 1).
HIV/AIDS patients, spouse HIV status, mode of transmission, Noticeably, statistically significant differences in descriptive
sample sources and baseline CD4+T cell counts was recorded. variables including the mode of transmission of HIV, sample
The criteria of AIDS-defining in the study include CD4+T sources, age at diagnosis and CD4+T cell counts at baseline before
countEpidemiology and Infection 3
Table 1. The covariates comparison between RPs and TPs before PSM
RPs TPs
Covariates n (%) n (%) χ2 P value
Gender 0.071 0.790
Male 923 (53.8) 201 (53.0)
Female 793 (46.2) 178 (47.0)
Contact with patients 14.0194 X. C. Jia et al.
Table 2. Patient’s demographic characteristics before and after PSM
Before matching After matching
Variables RPs (n = 1716) TPs (n = 379) Z/χ 2 P value RPs (n = 379) TPs (n = 379) Z/χ 2 P value
Occupation 9.001 0.003 0.164 0.686
Farmer 1653 (96.3) 352 (92.9) 349 (92.1) 352 (92.9)
Others 63 (3.7) 27 (7.1) 30 (7.9) 27 (7.1)
Marital status 11.958 0.003 6.293 0.098
Married 1205 (70.2) 241 (63.6) 238 (62.8) 241 (63.6)
Divorced or widowed 408 (23.8) 98 (25.9) 116 (30.6) 98 (25.9)
Unmarried 103 (6.0) 40 (10.6) 25 (6.6) 40 (10.6)
Education level 4.970 0.174 12.890 0.045
Illiteracy 161 (9.4) 26 (6.9) 47 (12.4) 26 (6.9)
Primary school 729 (42.5) 163 (43.0) 159 (42.0) 163 (43.0)
Junior high school 781 (45.5) 174 (45.9) 148 (39.1) 174 (45.9)
Senior high school or above 45 (2.6) 16 (4.2) 25 (6.6) 16 (4.2)
Mode of transmission 51.930Epidemiology and Infection 5
Table 3. Univariate and multivariate analyses of the factors associated with natural disease progression of HIV infections
Univariable analyses Multivariable analyses
Variables OR (95% CI) P value OR (95% CI) P value
Occupation 0.686
Farmer 1.00
Others 0.90 (0.53–1.55)
Marital status 0.100
Married 1.00
Divorced or widowed 0.85 (0.62–1.17) 0.316
Unmarried 1.56 (0.92–2.65) 0.100
Education level 0.024
Illiteracy 1.00
Primary school 1.82 (1.06–3.10) 0.029
Junior high school 2.08 (1.23–3.51) 0.006
Senior high school or above 1.15 (0.53–2.54) 0.720
Mode of transmission 0.001 0.018
Blood transmission 1.00 1.00
Sexual transmission 0.54 (0.39–0.75)6 X. C. Jia et al.
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