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

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https://doi.org/10.1017/S0950268820000540
2                                                                                                                                                             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
          count
Epidemiology 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                                                                                                             14.019
4                                                                                                                                                             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                                                             51.930
Epidemiology 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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