High-grade anal intraepithelial neoplasia is associated with HIV-1 RNA rectal shedding in virologically suppressed MSM

García‐Payá, Elena; Fernández, Marta; Padilla, Sergio; García, José Alberto; Robledano, Catalina; Tabla, Victoria Ortiz de la; Gutiérrez, Félix; Masiá, Mar

doi:10.1097/qad.0000000000001794

Cited by 5 publications

(8 citation statements)

References 26 publications

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“…HIV negative individuals with STIs, on the other hand, may be at increased risk of HIV acquisition due to infiltration of the infection site with susceptible inflammatory cells including CD4+ cells. Persistent HIV RNA shedding in the anorectal mucosa despite undetectable systemic viral load has been reported in association with co-existence of other STIs, possibly increasing the risk of infecting a discordant partner (García-Payá et al, 2018, Jansen et al, 2011. Despite the evidence that genitourinary Ureaplasma spp.…”

Section: Discussionmentioning

confidence: 99%

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections

Borena

Kruis

Kitchen

et al. 2019

International Journal of Infectious Diseases

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Objective: HIV positive individuals, particularly men having sex with men (MSM), are at increased risk of sexually transmitted infections (STIs) at genital and extra-genital sites. Data on anorectal Ureaplasma infections are lacking. The aim of our study was to characterize anal Ureaplasma positivity among a cohort of HIV positive MSM and evaluate possible association with papillomavirus infection at the same site. Methods: Anal swab samples, collected as part of routine screening for Chlamydia trachomatis and Neisseria gonorrhea, were additionally tested for HPV genotypes as well as for Ureaplasma and Mycoplasma using nucleic acid amplification method. Results: Out of a total of 222 study participants, 195 (89%, 95% CI (84.9-93.2)) were positive for HPV, approximately three quarter being high-risk genotypes. Forty three individuals (19.4%,3)) harbored Ureaplasma spp. Infection with high-risk HPV types was significantly associated with copresence of Ureaplasma with an odds ratio (95% confidence-interval) of 2.59 (1.03-6.54), P = 0.04. Conclusion: Besides a high predominance of HPV infection, asymptomatic HIV positive MSM had a high prevalence of anal Ureaplasma positivity. Concomitant infections with high-risk HPV genotypes were common and statistically significant. The role of this co-existence as a potential risk factor for anal carcinogenesis needs further elucidation.

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Section: Discussionmentioning

confidence: 99%

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections

Borena

Kruis

Kitchen

et al. 2019

International Journal of Infectious Diseases

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“…Different antiretroviral agents penetrate mucosal tissues with varying efficiency,9 and anal HIV RNA shedding was previously linked to a protease inhibitor-based regimen4; therefore, we assessed the association between ART components and anal HIV RNA shedding. Of the 51 participants whose ART regimen components were known at the time of study enrolment, 40 (78.4%) included an integrase inhibitor and 17 (33.3%) a boosted protease inhibitor.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, inflammation induced by STIs can increase mucosal HIV shedding2 and therefore increase HIV transmission risk. While effective antiretroviral therapy (ART) reduces HIV transmission risk to a negligible level in real-world studies,3 relatively few studies have addressed the potential effect of STIs on anal HIV shedding in the context of ART 4 5…”

Section: Introductionmentioning

confidence: 99%

“…Of note, anal HPV infection is highly prevalent among men who have sex with men (MSM), and its progression to anal intraepithelial neoplasia (AIN) is particularly common in MSM living with HIV 6. In addition, high-grade AIN (HGAIN), the direct precursor to anal cancer, has been associated with anorectal HIV RNA shedding despite ART 4. Therefore, we conducted a cross-sectional study in HIV-infected, ART-treated MSM to investigate the potential impact of AIN on anal HIV RNA shedding.…”

Section: Introductionmentioning

confidence: 99%

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Anal dysplasia and HIV shedding in ART-treated men

et al. 2020

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ObjectivesAnal human papillomavirus (HPV) infection is highly prevalent among men who have sex with men (MSM). HPV-associated anal dysplasia has been linked with anal HIV RNA shedding despite antiretroviral therapy (ART). Since mucosal HIV levels are a key determinant of sexual transmission of the virus, this would have important public health implications. Therefore, we assessed the association between anal dysplasia and HIV shedding in ART-treated MSM from Toronto, Canada.MethodsIn 54 HIV-infected men on effective ART, we assessed anal HIV RNA shedding by PCR, HPV infection by microsphere-based genotyping and anal dysplasia by high-resolution anoscopy. All participants were enrolled between May 2017 and October 2018.ResultsThe median duration of ART at the time of study enrolment was 18 years, with most participants being on an integrase inhibitor-based ART regimen. Low-level anal HIV RNA shedding was present in 15/54 (27.8%) participants. Neither the detection of shedding nor the level of HIV RNA was associated with anal dysplasia, HPV infection or antiretroviral regimen.ConclusionsHPV-associated anal dysplasia was not associated with anal HIV RNA shedding in this relatively small cohort of men on effective ART. While anal HIV RNA was detected more often than anticipated, shedding was low level and unlikely to cause HIV transmission. However, the immunological drivers of anal HIV RNA shedding in ART-treated individuals may merit further study.

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“…Although using different methods and measures to address diversity, similarly to our study, HIV diversity was consistently higher in these compartments than in blood. García-Payá et al 29 reported a higher HIV-1 RNA rectal shedding in virologically suppressed MSM, suggesting that blood HIV-1 RNA measurements may not necessarily reflect the viral concentrations at the rectal reservoir. No certain explanation to the greater viral diversity in seminal plasma than in the blood is available to date; a possible cause could be a lower immune selection in the genitourinary tract compared with blood and, therefore, a lower purifying selection in the seminal plasma.…”

Section: Discussionmentioning

confidence: 99%

Genetic diversity of HIV in seminal plasma remains higher than in blood after short-term antiretroviral therapy

Zúñiga¹,

Caproş

Salazar

et al. 2020

Sex Transm Infect

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ObjectiveTo provide insight on viral kinetics and genetic diversity of HIV in seminal plasma at baseline and 1 month after initiating antiretroviral therapy (ART).Patients and methodsBlood and seminal samples from patients with newly diagnosed HIV were obtained before ART initiation (T0) and 1 month after ART initiation (T1). HIV env genetic diversity was studied using deep sequencing Nextera and V3 chemistry in a MiSeq Illumina platform. The number of viral quasispecies (5% cut-off) and Shannon Index were used to analyse diversity.ResultsForty-seven ART-naive patients were recruited between September 2016 and November 2018. At enrolment, the number of quasispecies in blood (median 4 (IQR 2–5)) was lower than in the seminal compartment (median 6, (IQR 4–8)) (p<0.01); the Shannon Index was also higher (p<0.001) in the seminal compartment than in blood (1.77 vs 0.64). At T1, for the 13 patients with detectable HIV in both blood/seminal plasma, viral diversity remained higher (p=0.139) in seminal plasma (median 2 (IQR 1–4.5)) than in blood (median 1 (IQR 1–1.5)) Integrase inhibitors (INI)-based regimens achieved higher levels of undetectability and led more frequently to lower variability (p<0.001) than protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI).ConclusionWe provide here further evidence of a larger genetic diversity in seminal plasma, both at diagnosis and short term after ART initiation. Our results strengthen previous findings on HIV diversity in seminal plasma. In addition, INIs decrease variability more rapidly than PI and NNRTI in both blood and seminal plasma.

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High-grade anal intraepithelial neoplasia is associated with HIV-1 RNA rectal shedding in virologically suppressed MSM

Abstract: The prevalence of HIV-1 RNA rectal shedding is high in virologically suppressed MSM. In addition to ART and the immune system integrity, local factors, including the co-existence of HG-AIN and the burden of STIs, may account for the persistence of HIV-1 RNA shedding in rectal mucosa.

Cited by 5 publications

References 26 publications

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections

Anal dysplasia and HIV shedding in ART-treated men

Genetic diversity of HIV in seminal plasma remains higher than in blood after short-term antiretroviral therapy

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