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Background: Cellular immune responses characterized by interferon gamma (IFN-gamma) production enhance clearance and confer protective immunity against Chlamydia trachomatis infection but have not been simultaneously investigated in systemic and mucosal compartments.Methods: With use of the IFN-gamma enzyme-linked immunosorbent spot assay, we investigated immune responses to Chlamydia elementary body (EB) and 3 genotypically variant heat shock protein 60 (CHSP60) antigens using peripheral blood mononuclear cells and endometrial mononuclear cells obtained from a female sex worker cohort with high levels of exposure to C. trachomatis.Results: Although we observed a marginally higher frequency of IFN-gamma responses to EB in peripheral blood mononuclear cells, compared with the frequency in endometrial mononuclear cells, the magnitudes of systemic and mucosal responses were similar except for preferential targeting of CHSP60 type 2 by endometrial mononuclear cells. Systemic and mucosal responses were highly correlated for EB and CHSP60 types 1 and 2 but not type 3. The frequency and magnitude of systemic responses specific for EB and CHSP60 type 1 were greater for CD4+ T cells than they were for CD8+ T cells, whereas preferential targeting by CHSP60 types 2 and 3 was undetectable. IFN-gamma response to CHSP60 type 1 by peripheral blood mononuclear cells was inversely correlated with systemic antibody titers to CHSP60 type 1.Conclusion: Systemic and mucosal IFN-gamma responses are correlated, with preferential systemic targeting of CD4+ T cells. Furthermore, CHSP60 type 1 response is largely CD4+ T cell mediated and follows discrete T helper 1 and T helper 2 pathways. [ABSTRACT FROM AUTHOR]

Background: In 2022, the global dissemination of mpox virus (MPXV) outside endemic regions prompted the expansion of diagnostic testing worldwide. This study assesses the performance characteristics of 5 real-time polymerase chain reaction (PCR) assays in detecting MPXV during the 2022 outbreak., Methods: Clinical specimens collected from patients across Ontario, Canada, were tested on the following assays: RealStar Orthopoxyvirus PCR and FlexStar Monkeypox virus PCR (Altona Diagnostics), Novaplex MPXV (Seegene), VIASURE Monkeypox virus Real Time PCR Reagents (CerTest Biotec), and a laboratory-developed test. Positive percent agreement (PPA), negative percent agreement (NPA), relative limit of detection (LOD), and precision were evaluated and MPXV lineages were determined using an amplicon-based whole-genome sequencing (WGS) assay., Results: Swabs were collected from various anatomic sites (65 positive and 30 negative). All assays demonstrated 100% NPA (95% confidence interval, 88.4%/88.1%-100.0%), with PPA ranging from 92.2% (82.7%-97.4%) to 96.9% (89.3%-99.6%). LOD and precision were comparable across assays, with coefficient of variations <3%. WGS analysis identified 6 lineages, all belonging to subclade IIb., Conclusions: The assays exhibited excellent PPA, NPA, LOD, and precision. Ongoing performance monitoring is essential to detect assay escape mutants and ensure universal detection of evolving MPXV strains., Competing Interests: Potential conflicts of interest. K. B. and L. M. M. and received PCR kits in kind from Altona Diagnostics Canada, Seegene Canada, and BD Canada. L. M. M. is the president of the board of the Canadian Foundation for Infectious Diseases. R. K. and P. M. S. are recipients of financial support from the University of Toronto EPIC Mpox grant. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Effective antiretroviral therapy (ART) dramatically reduces human immunodeficiency virus (HIV) transmission. However, isolated shedding of HIV type 1 (HIV-1) in semen (IHS) can occur in the absence of detectable viremia or genital infections. We hypothesized that ART intensification with medications active in semen might prevent IHS., Methods: Paired blood and semen samples were collected monthly for 6 months from HIV-infected men starting ART that was intensified (iART) with maraviroc and raltegravir in an open-label fashion. Semen parameters were compared to those of historical controls starting standard ART (sART)., Results: Compared with 25 controls who started sART, the semen HIV-1 load in 13 subjects who started iART was more rapidly suppressed (P = .043). IHS was detected at >1 visit in 2 participants (15%) receiving iART and in 12 controls (48%) receiving sART (P = .040). Among iART recipients, IHS was associated with lower raltegravir concentrations in blood and semen, compared with complete HIV-1 suppression (P = .03). Prolonged, high-level IHS (ie, shedding of >5000 RNA copies/mL) was observed in 1 iART recipient (8%), despite rapid viremia suppression and therapeutic drug levels; for 10 months, this virus remained R5 tropic, drug susceptible, and similar in sequence to virus recovered from blood. IHS was not seen after >3 years of effective ART in a parallel, prospective cohort study., Conclusions: iART transiently reduced the occurrence of IHS early after ART initiation but did not prevent high-level IHS. IHS was not seen after more prolonged sART.

Background: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity., Methods: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry., Results: The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells., Conclusions: HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.

Semen transmission of human immunodeficiency virus (HIV) drives the global pandemic. HIV loads are generally lower in semen than in blood, but semen loads may be disproportionately high in a subgroup of men. HIV loads in semen exceeded those in blood in 9 (35%) of 26 of antiretroviral therapy-naive men, and disproportionately high shedding was strongly associated with compartmentalized semen cytomegalovirus (CMV) reactivation (odds ratio [OR], 10.5; P<.01). Overall, 17 of 26 participants were shedding CMV in semen. Semen levels of HIV and CMV were closely correlated (r=0.5; P<.01), independently of blood HIV load and CD4(+) T cell count. Prevention of CMV reactivation warrants further study as a possible strategy to reduce semen shedding of HIV.