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An abstract of the article "Loss of Viral Control in a Subset of HIV-Infected Long-term Non-progressors Is Associated with a Decline of an Array of Antiviral Responses" by Mohamed El-Far, Pascale Kouassi, Odalis Asin-Milan, and colleagues is presented.

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH., Competing Interests: Potential conflicts of interest. All authors: No reported 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) 2023. 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: Persistent inflammation in HIV infection is associated with elevated cardiovascular disease (CVD) risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance CVD risk stratification and suggest novel therapies. We investigated the potential of interleukin 32 (IL-32), a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically suppressed women living with HIV (WLWH)., Methods and Results: Nested within the Women's Interagency HIV Study, we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, ε, and θ) was quantified by reverse transcription polymerase chain reaction from peripheral blood mononuclear cells. Plasma IL-32 protein levels were higher in WLWH compared with women without HIV (P = 0.02). Among WLWH, although plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β, and ε mRNA was significantly higher in peripheral blood mononuclear cells from cases (P = 0.01, P = 0.005, and P = 0.018, respectively). Upregulation of IL-32β and IL-32ε among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (P = 0.04 and P = 0.045); the adjusted association for IL-32α was marginally significant (P = 0.07)., Conclusions: IL-32 isoforms should be studied further as potential CVD biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population., Competing Interests: J.R.K. has stock ownership in Bristol-Myers Squibb, Johnson & Johnson, Medtronic, Merck, and Pfizer. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8 + T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8 + T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8 + T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8 + T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8 + T-cell senescence and dysfunction in PLWH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bunet, Nayrac, Ramani, Sylla, Durand, Chartrand-Lefebvre, Routy, Landay, Gauchat, Chomont, Ancuta, Kaufmann, Bernard, Tremblay and El-Far.)

Background: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4 T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory., Setting and Methods: Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4 T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4 T-cells from HIV-1cART individuals by qRT-PCR., Results: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4 T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4 T-cells isolated from combined antiretroviral therapy-treated individuals., Conclusions: Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.

Our study aimed to evaluate the outcome of the surgical treatment of appendicular plastron after deferred or emergency appendectomy. We conducted a retrospective, descriptive study of 27 patients treated for appendicular plastron from January 2000 to 31 December 2007. Diagnosis was based on clinical examination showing a mass in the right iliac fossa, on ultrasound or made intraoperatively. All patients undergoing emergency surgery were classified in Group I while those undergoing deferred surgery were classified in Group II. 18 men and 9 women were registered, with a sex-ratio man /Woman=2. The average age of patients was 33 years, ranging between 19 and 57 years. Clinical signs were dominated by pain in the right iliac fossa and fever in 25(92.6%) and 15 (55.6%) of cases respectively. In group I, appendectomy couldn't be performed in 7 cases (n= 15) due to surgical complications. In all other cases appendectomy was performed by enlarging Mac Burney's incision and was associated with longer length of stay in hospital. Group II included 12 patients (n=12), 9 underwent laparoscopy and 3 patients underwent Mac Burney's incision. 3 cases with peritoneal adhesions were detected during coelioscopy. Deferred appendectomy of appendicular plastron is a safe and efficient surgical procedure. It allows to avoid unattractive scarrings and iatrogenic digestive fistulas. Emergency appendectomy shouldn't be performed in patients with appendicular plastron because it increases the risks of morbidity.

Background: Sub-Saharan Africa has seen dramatic increases in the numbers of people treated with antiretroviral therapy (ART). Although standard ART regimens are now universally applied, viral load measurement is not currently part of standard monitoring protocols in sub-Saharan Africa., Methods: We describe the prevalence of inadequate virological response (IVR) to ART (viral load >or= 500 copies/mL) and identify factors associated with this outcome in 606 HIV-positive patients treated for at least 6 months. Recruitment took place in 7 hospitals and community-based sites in Bamako and Ouagadougou, and information was collected using medical charts and interviews., Results: The overall prevalence of IVR in treatment-naive patients was 12.3% and 24.4% for pretreated patients. There were no differences in rates of IVR according to ART delivery sites and time on treatment. Patients living farther away [odds ratio (OR) = 2.48; 95% confidence interval (CI) 1.40 to 4.39], those on protease inhibitor or nucleoside reverse transcriptase inhibitor regimens (OR = 3.23; 95% CI 1.79 to 5.82) and those reporting treatment interruptions (OR = 2.36; 95% CI 1.35 to 4.15), had increased odds of IVR. Immune suppression (OR = 3.32, 95% CI 1.94 to 5.70) and poor self-rated health (OR = 2.00; 95% CI 1.17 to 3.41) were also associated with IVR., Conclusions: Sufficient expertise and dedication exist in public hospital and community-based programs to achieve rates of treatment success comparable to better-resourced settings.

Objectives: the objectives of this study were, in healthcare facilities in six countries in West Africa, to: (1) estimate the proportion of patients consulting for sexually transmitted diseases (STDs) for whom an adequate case history was taken and who received an appropriate physical examination and effective treatement (prevention indicator PI6); (2) to determine the percentage of patients who were given advice on condom use and notification of sexual partners for STD treatment (prevention indicator PI7); (3) to determine the level of knowledge of healthcare workers concerning STD case management; and (4) to compare reported and observed behaviour regarding STD case management by healthcare workers., Material and Method: this descriptive study was carried out in 240 health care facilities in six countries: Benin, Burkina Faso, Côte d'Ivoire, Guinea, Mali, and Senegal, using the WHO protocol for PI6 and PI7 indicators to evaluate the quality of management of urethral discharge and genital ulcers, as well as an extension of this protocol to evaluate STD syndromes specific to women, namely vaginal discharge and pelvic inflammatory disease. Healthcare workers were observed during STD consultations, and thereafter interviewed. Up to five observations per healthcare worker were carried out over a period of three days spent at each health care facility. Criteria for an adequate case history were inclusion of questions on the nature, time of initiation and duration of symptoms, and for physical examination, visualisation and examination of genital organs for discharge and lesions. Treatments prescribed were judged as effective when in conformity with national algorithms for syndromic STD management. The PI6 indicator was estimated as the proportion of cases where an adequate case history was taken, an appropriate physical examination carried out and effective treatment prescribed. The PI7 score corresponded to the percentage of patients who received advice on condom use and partner notification for treatment. In order to control for intra-healthcare-worker correlation, the SUUDAN software was used for the computation of 95% confidence intervals of the proportions, obtained from univariate analysis in EPI-INFO, and for the comparison of the PI6 and PI7 scores by country, sex, marital status and symptoms of the patient, as well as by level of qualification of the healthcare workers, using the khi2 test., Results: overall, 613 observations and 504 interviews of 263 healthcare workers were carried out. The majority of STD patients were female (57.1%) and unmarried (53.0%). Healthcare workers were most frequently doctors (33.6%) and the most common complaint was vaginal discharge (42.2%). Intercountry variation was observed for all these variables. An adequate case history was taken in 84.6% of cases and an adequate physical examination carried out in 60.8% of cases. Healthcare workers gave a diagnosis in conformity with national syndromic STD management algorithms in 35.3% of cases, while effective treatment was given to 14.1% of patients. Patients were encouraged to use condoms in 19.5% of cases and to advise their partners to seek treatment in 50.8% of cases; this advice was given more frequently to men than to women. PI6 and PI7 scores were respectively 9.9% (95% CI: 6.9%; 12.9%) and 15.4% (95% CI: 11.4%; 19.2%). Healthcare workers' knowledge of effective STD treatment regimes was low. Practices reported during interviews with regard to STD patients were comparable to observed behaviour with regard to case history-taking and physical examination, but not for diagnosis and treatment nor for condom promotion or partner notification advice., Conclusion: the results of this study demonstrate the low quality of STD management in the six countries evaluated, which may be explained by the lack of availability of examination material, the inadequate knowledge of healthcare workers, as well as the infrequent promotion of STD prevention methods, particularly in women.