CoChat
Sign Up
Cited by 131Syphilis Diagnosis and TreatmentHIV/AIDS Research and InterventionsHIV, Drug Use, Sexual Risk

Effect of syphilis infection on HIV acquisition: a systematic review and meta-analysis

Open access
Wu, Meng Yin, Gong, Hui Zi, Hu, Kui Ru, Zheng, He-yi, Wan, Xia, Li, Jun·2021·Sexually Transmitted Infections
DOI 10.1136/sextrans-2020-054706PMC PMC8543214
Open this paper in CoChat — free accountOpen PDF

Abstract

OBJECTIVES: Co-infection of syphilis and HIV remains hard to manage and its morbidity shows a rising tendency. Syphilis has been associated with increased risk of HIV acquisition in high-risk groups, especially in men who have sex with men (MSM). This systematic review and meta-analysis estimates the effect of syphilis infection on subsequent HIV acquisition, and assesses its difference between MSM and other high-risk populations. METHODS: Five electronic databases were searched for literature published to 21 September 2019 without language restrictions. Longitudinal studies that enrolled key populations to compare the incidence of HIV with and without syphilis exposure were included. We used a random-effects model to estimate the effect of syphilis infection on HIV acquisition among high-risk populations, which include MSM, sex workers, serodiscordant couples, people who inject drugs and attendees of STD clinics. RESULTS: A total of 17 cohorts and 5 case-control studies involving 65 232 participants were included. HIV incidence showed a two-time increase after syphilis exposure, compared with a control group (relative risk (RR) 2.67 (95% CI 2.05 to 3.47); p<0.05 for prevalence; RR 3.21 (95% CI 2.26 to 4.57); p=0.419 for incidence). No significant differences were observed between MSM and other high-risk groups in syphilis infection prevalence (RR 2.60 (95% CI 1.78 to 3.80); p<0.05 vs RR, 2.98 (95% CI 2.15 to 4.14); p<0.05; ratio of relative risk 0.76 (95% CI 0.49 to 1.17)). CONCLUSIONS: Syphilis infection increases the risk of HIV acquisition in high-risk populations. There is no evidence to suggest MSM are at greater risk than other high-risk populations. Prompt diagnosis, timely treatment, preventive interventions against syphilis infection would be a worthwhile investment for reducing HIV incidence. Strategies to combat stigma and discrimination targeted at MSM are pragmatically needed.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/sextrans-2020-054706

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 44

  1. [2]Read P, Fairley CK, Chow EPF. Increasing trends of syphilis among men who have sex with men in high income countries. Sex Health 2015; 12: 155– 63. 10.1071/SH14153 25607751 · DOI
  2. [4]Zetola NM, Klausner JD. Syphilis and HIV infection: an update. Clin Infect Dis 2007; 44: 1222– 8. 10.1086/513427 17407043 · DOI
  3. [5]Jansen K, Schmidt AJ, Drewes J, et al. Increased incidence of syphilis in men who have sex with men and risk management strategies, Germany, 2015. Euro Surveill. 2016; 21: 30382. 10.2807/1560-7917.ES.2016.21.43.30382 PMC5114722 27813472 · DOI
  4. [6]Wu Z, Xu J, Liu E, et al. Hiv and syphilis prevalence among men who have sex with men: a cross-sectional survey of 61 cities in China. Clin Infect Dis 2013; 57: 298– 309. 10.1093/cid/cit210 23580732 PMC3689345 · DOI
  5. [7]Li H-M, Peng R-R, Li J, et al. Hiv incidence among men who have sex with men in China: a meta-analysis of published studies. PLoS One 2011; 6: e23431. 10.1371/journal.pone.0023431 21887251 PMC3162552 · DOI
  6. [8]Feng Y, Bu K, Li M, et al. [Meta-analysis of HIV infection incidence and risk factors among men who have sex with men in China]. Zhonghua Liu Xing Bing Xue Za Zhi 2015; 36: 752– 8. 26564708
  7. [9]Arora P, Nagelkerke NJD, Jha P. A systematic review and meta-analysis of risk factors for sexual transmission of HIV in India. PLoS One 2012; 7: e44094. 10.1371/journal.pone.0044094 22937158 PMC3429412 · DOI
  8. [10]Greenwood DC. Meta-analysis of observational studies. Modern Methods for Epidemiology 2012; 10: 173– 89.
  9. [12]DerSimonian R, Laird N. Meta-Analysis in clinical trials revisited. Contemp Clin Trials 2015; 45: 139– 45. 10.1016/j.cct.2015.09.002 26343745 PMC4639420 · DOI · Paper page
  10. [13]Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003; 326: 219. 10.1136/bmj.326.7382.219 12543843 PMC1125071 · DOI · Paper page
  11. [14]Desai S, Nardone A, Hughes G, et al. Hiv incidence in an open national cohort of men who have sex with men attending sexually transmitted infection clinics in England. HIV Med 2017; 18: 615– 22. 10.1111/hiv.12498 28127837 · DOI
  12. [15]van Griensven F, Thienkrua W, McNicholl J, et al. Evidence of an explosive epidemic of HIV infection in a cohort of men who have sex with men in Thailand. AIDS 2013; 27: 825– 32. 10.1097/QAD.0b013e32835c546e 23169330 · DOI
  13. [16]Jin F, Prestage GP, Imrie J, et al. Anal sexually transmitted infections and risk of HIV infection in homosexual men. J Acquir Immune Defic Syndr 2010; 53: 144– 9. 10.1097/QAI.0b013e3181b48f33 19734801 · DOI
  14. [17]Ferrer L, Loureiro E, Meulbroek M, et al. High HIV incidence among men who have sex with men attending a community-based voluntary counselling and testing service in Barcelona, Spain: results from the ITACA cohort. Sex Transm Infect 2016; 92: 70– 5. 10.1136/sextrans-2015-052042 26136507 · DOI
  15. [18]Beymer MR, Weiss RE, Sugar CA, et al. Are centers for disease control and prevention guidelines for preexposure prophylaxis specific enough? formulation of a personalized HIV risk score for pre-exposure prophylaxis initiation. Sex Transm Dis 2017; 44: 49– 57. 10.1097/OLQ.0000000000000535 PMC5145736 27898570 · DOI
  16. [19]Beymer MR, Weiss RE, Halkitis PN, et al. Disparities within the Disparity-Determining HIV risk factors among Latino gay and bisexual men attending a community-based clinic in Los Angeles, Ca. J Acquir Immune Defic Syndr 2016; 73: 237– 44. 10.1097/QAI.0000000000001072 27163174 PMC5025341 · DOI
  17. [20]Guy RJ, Spelman T, Stoove M, et al. Risk factors for HIV seroconversion in men who have sex with men in Victoria, Australia: results from a sentinel surveillance system. Sex Health 2011; 8: 319– 29. 10.1071/SH10095 21851771 · DOI
  18. [21]Marcus U, Bremer V, Hamouda O, et al. Understanding recent increases in the incidence of sexually transmitted infections in men having sex with men: changes in risk behavior from risk avoidance to risk reduction. Sex Transm Dis 2006; 33: 11– 17. 10.1097/01.olq.0000187224.10428.31 16385216 · DOI
  19. [22]Xu J, An M, Han X, et al. Prospective cohort study of HIV incidence and molecular characteristics of HIV among men who have sex with men (MSM) in Yunnan Province, China. BMC Infect Dis 2013; 13: 3. 10.1186/1471-2334-13-3 23286213 PMC3599414 · DOI
  20. [23]Xu J-J, Zhang M, Brown K, et al. Syphilis and HIV seroconversion among a 12-month prospective cohort of men who have sex with men in Shenyang, China. Sex Transm Dis 2010; 37: 432– 9. 10.1097/OLQ.0b013e3181d13eed 20375928 PMC5454492 · DOI
  21. [24]Yang H, Hao C, Huan X, et al. Hiv incidence and associated factors in a cohort of men who have sex with men in Nanjing, China. Sex Transm Dis 2010; 37: 1– 213. 10.1097/OLQ.0b013e3181d13c59 20182406 · DOI
  22. [25]Yang Z, Huang Z, Dong Z, et al. Risk factors for HIV diagnosis among men who have sex with men: results of a case-control study in one sample of eastern China. AIDS Res Hum Retroviruses 2016; 32: 1163– 8. 10.1089/aid.2016.0031 27329367 · DOI
  23. [26]Riedner G, Hoffmann O, Rusizoka M, et al. Decline in sexually transmitted infection prevalence and HIV incidence in female barworkers attending prevention and care services in Mbeya region, Tanzania. AIDS 2006; 20: 609– 15. 10.1097/01.aids.0000210616.90954.47 16470126 · DOI
  24. [27]Lee PM, Ho KM. Risk factors associated with human immunodeficiency virus (HIV) infection among Attendees of public sexually transmitted infection clinics in Hong Kong: implications for HIV prevention. Hong Kong Med J 2008; 14: 259– 66. 18685157
  25. [28]Mehta SD, Ghanem KG, Rompalo AM, et al. Hiv seroconversion among public sexually transmitted disease clinic patients: analysis of risks to facilitate early identification. J Acquir Immune Defic Syndr 2006; 42: 116– 22. 10.1097/01.qai.0000200662.40215.34 16763500 · DOI
  26. [29]Ruzagira E, Wandiembe S, Abaasa A, et al. Hiv incidence and risk factors for acquisition in HIV discordant couples in Masaka, Uganda: an HIV vaccine preparedness study. PLoS One 2011; 6: e24037. 10.1371/journal.pone.0024037 21909379 PMC3166075 · DOI
  27. [30]Su Y, Ding G, Reilly KH, et al. Loss to follow-up and HIV incidence in female sex workers in Kaiyuan, Yunnan Province China: a nine year longitudinal study. BMC Infect Dis 2016; 16: 526. 10.1186/s12879-016-1854-y 27686152 PMC5041379 · DOI
  28. [31]Li D, Jia Y, Ruan Y, et al. Correlates of incident infections for HIV, syphilis, and hepatitis B virus in a cohort of men who have sex with men in Beijing. AIDS Patient Care STDS 2010; 24: 595– 602. 10.1089/apc.2010.0083 20731610 PMC2957630 · DOI
  29. [32]Li D, Li S, Liu Y, et al. Hiv incidence among men who have sex with men in Beijing: a prospective cohort study. BMJ Open 2012; 2: 001829. 10.1136/bmjopen-2012-001829 PMC3533041 23166133 · DOI
  30. [33]Tang W, Babu GR, Li J, et al. The difference between HIV and syphilis prevalence and incidence cases: results from a cohort study in Nanjing, China, 2008-2010. Int J STD AIDS 2015; 26: 648– 55. 10.1177/0956462414550170 25249593 PMC4370797 · DOI
  31. [34]Wang Q-Q, Chen X-S, Yin Y-P, et al. Hiv prevalence, incidence and risk behaviours among men who have sex with men in Yangzhou and Guangzhou, China: a cohort study. J Int AIDS Soc 2014; 17: 18849. 10.7448/IAS.17.1.18849 25103308 PMC4188039 · DOI
  32. [35]Braunstein SL, Ingabire CM, Kestelyn E, et al. High human immunodeficiency virus incidence in a cohort of Rwandan female sex workers. Sex Transm Dis 2011; 38: 385– 94. 10.1097/OLQ.0b013e31820b8eba 22256340 · DOI
  33. [37]Lafond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev 2006; 19: 29– 49. 10.1128/CMR.19.1.29-49.2006 16418521 PMC1360276 · DOI · Paper page
  34. [38]Rekart ML, Ndifon W, Brunham RC, et al. A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum? Sex Transm Infect 2017; 93: 374– 8. 10.1136/sextrans-2016-052870 28093460 PMC5537507 · DOI
  35. [39]Radolf JD, Deka RK, Anand A, et al. Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nat Rev Microbiol 2016; 14: 744– 59. 10.1038/nrmicro.2016.141 27721440 PMC5106329 · DOI
  36. [40]Salazar JC, Cruz AR, Pope CD, et al. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis 2007; 195: 879– 87. 10.1086/511822 17299719 PMC2131710 · DOI
  37. [41]Marra CM, Tantalo LC, Sahi SK, et al. Reduced Treponema pallidum-specific opsonic antibody activity in HIV-infected patients with syphilis. J Infect Dis 2016; 213: 1348– 54. 10.1093/infdis/jiv591 26655298 PMC4799670 · DOI
  38. [42]Lukehart SA, Shaffer JM, Baker-Zander SA. A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence. J Infect Dis 1992; 166: 1449– 53. 10.1093/infdis/166.6.1449 1431264 · DOI
  39. [43]Fitzgerald TJ. The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infect Immun 1992; 60: 3475– 9. 10.1128/IAI.60.9.3475-3479.1992 1386838 PMC257347 · DOI
  40. [44]Sellati TJ, Wilkinson DA, Sheffield JS, et al. Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1. J Infect Dis 2000; 181: 283– 93. 10.1086/315209 10608777 · DOI
  41. [45]Theus SA, Harrich DA, Gaynor R, et al. Treponema pallidum, lipoproteins, and synthetic lipoprotein analogues induce human immunodeficiency virus type 1 gene expression in monocytes via NF-kappaB activation. J Infect Dis 1998; 177: 941– 50. 10.1086/515240 9534966 · DOI
  42. [46]Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996; 381: 661– 6. 10.1038/381661a0 8649511 · DOI
  43. [47]Dragic T, Litwin V, Allaway GP, et al. Hiv-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381: 667– 73. 10.1038/381667a0 8649512 · DOI
  44. [48]Bentwich Z, Maartens G, Torten D, et al. Concurrent infections and HIV pathogenesis. AIDS 2000; 14: 2071– 81. 10.1097/00002030-200009290-00002 11061647 · DOI

Cited by

Sorted by citations

Authors
Wu, M. Y., Gong, H. Z., Hu, K. R., Zheng, H.-Y., Wan, X., & Li, J.
Affiliations
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Li, Jun
ORCID
Venue
Sexually Transmitted Infections
Publisher
BMJ
Published
2020-11-20
Volume
97
Issue
7
Pages
525-533
ISSN
  • 0007-134X (ISSN-L)
  • 1368-4973
  • 1472-3263
DOI
10.1136/sextrans-2020-054706
PMC
PMC8543214
OpenAlex
W3099383496
Cited by
131
References
2
Citations by year
2026: 19 · 2025: 35 · 2024: 28 · 2023: 21 · 2022: 21 · 2021: 7
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Sexually Transmitted Infections (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Beijing Municipal Science and Technology Commission (Z191100006619011)
Topics
  • Health Sciences › Medicine › Physiology › Syphilis Diagnosis and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
Keywords
syphilis, HIV acquisition, HIV-syphilis coinfection, men who have sex with men, vulnerable populations, sex workers, people who inject drugs, serodiscordant couples, STD clinic attendees, HIV incidence, syphilis prevalence, stigma and discrimination
MeSH terms
Humans, Male, Risk Factors, Syphilis, Cohort Studies, HIV Infections, Incidence, Prevalence, Databases, Factual, Homosexuality, Male

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review