Evolution of Antibodies to Native Trimeric Envelope and Their Fc-Dependent Functions in Untreated and Treated Primary HIV Infection.

People living with HIV (PLWH) develop both anti-envelope-specific antibodies, which bind the closed trimeric HIV envelope present on infected cells, and anti-gp120-specific antibodies, which bind gp120 monomers shed by infected cells and taken up by CD4 on uninfected bystander cells. Both antibodies have an Fc portion that binds to Fc receptors on several types of innate immune cells and stimulates them to develop antiviral functions. Among these Fc-dependent functions (FcDFs) are antibody-dependent (AD) cellular cytotoxicity (ADCC), AD cellular trogocytosis (ADCT), and AD phagocytosis (ADCP). In this study, we assessed the evolution of total immunoglobulin G (IgG), anti-gp120, and anti-envelope IgG antibodies and their FcDFs in plasma samples from antiretroviral therapy (ART)-naive subjects during early HIV infection (28 to 194 days postinfection [DPI]). We found that both the concentrations and FcDFs of anti-gp120 and anti-envelope antibodies increased with time in ART-naive PLWH. Although generated concurrently, anti-gp120-specific antibodies were 20.7-fold more abundant than anti-envelope-specific antibodies, both specificities being strongly correlated with each other and FcDFs. Among the FcDFs, only ADCP activity was inversely correlated with concurrent viral load. PLWH who started ART at >90 DPI showed higher anti-envelope-specific antibody levels and ADCT and ADCP activities than those starting ART at<90 DPI. However, in longitudinally collected samples, ART initiation at >90 DPI was accompanied by a faster decline in anti-envelope-specific antibody levels, which did not translate to a faster decline in FcDFs than for those starting ART at <90 DPI. IMPORTANCE Closed-conformation envelope is expressed on the surface of HIV-infected cells. Antibodies targeting this conformation and that support FcDFs have the potential to control HIV. This study tracked the timing of the appearance and evolution of antibodies to closed-conformation envelope, whose concentration increased over the first 6 months of infection. Antiretroviral therapy (ART) initiation blunts further increases in the concentration of these antibodies and their and FcDFs. However, antibodies to open-conformation envelope also increased with DPI until ART initiation. These antibodies target uninfected bystander cells, which may contribute to loss of uninfected CD4 cells and pathogenicity. This report presents, for the first time, the evolution of antibodies to closed-conformation envelope and their fate on ART. This information may be useful in making decisions on the timing of ART initiation in early HIV infection.

Influence of NKG2C Genotypes on HIV Susceptibility and Viral Load Set Point.

NKG2C is an activating NK cell receptor encoded by a gene having an unexpressed deletion variant. Cytomegalovirus (CMV) infection expands a population of NKG2C+ NK cells with adaptive-like properties. Previous reports found that carriage of the deleted NKG2C- variant was more frequent in people living with HIV (PLWH) than in HIV- controls unexposed to HIV. The frequency of NKG2C+ NK cells positively correlated with HIV viral load (VL) in some studies and negatively correlated with VL in others. Here, we investigated the link between NKG2C genotype and HIV susceptibility and VL set point in PLWH. NKG2C genotyping was performed on 434 PLWH and 157 HIV-exposed seronegative (HESN) subjects. Comparison of the distributions of the three possible NKG2C genotypes in these populations revealed that the frequencies of NKG2C+/+ and NKG2C+/- carriers did not differ significantly between PLWH and HESN subjects, while that of NKG2C-/- carriers was higher in PLWH than in HESN subjects, in which none were found (P = 0.03, χ2 test). We were unable to replicate that carriage of at least 1 NKG2C- allele was more frequent in PLWH. Information on the pretreatment VL set point was available for 160 NKG2C+/+, 83 NKG2C+/-, and 6 NKG2C-/- PLWH. HIV VL set points were similar between NKG2C genotypes. The frequency of NKG2C+ CD3- CD14- CD19- CD56dim NK cells and the mean fluorescence intensity (MFI) of NKG2C expression on NK cells were higher on cells from CMV+ PLWH who carried 2, versus 1, NKG2C+ alleles. We observed no correlations between VL set point and either the frequency or the MFI of NKG2C expression. IMPORTANCE We compared NKG2C allele and genotype distributions in subjects who remained HIV uninfected despite multiple HIV exposures (HESN subjects) with those in the group PLWH. This allowed us to determine whether NKG2C genotype influenced susceptibility to HIV infection. The absence of the NKG2C-/- genotype among HESN subjects but not PLWH suggested that carriage of this genotype was associated with HIV susceptibility. We calculated the VL set point in a subset of 252 NKG2C-genotyped PLWH. We observed no between-group differences in the VL set point in carriers of the three possible NKG2C genotypes. No significant correlations were seen between the frequency or MFI of NKG2C expression on NK cells and VL set point in cytomegalovirus-coinfected PLWH. These findings suggested that adaptive NK cells played no role in establishing the in VL set point, a parameter that is a predictor of the rate of treatment-naive HIV disease progression.

Human papillomavirus genotype concordance between Anyplex II HPV28 and linear array HPV genotyping test in anogenital samples.

Anyplex II HPV-28 (HPV-28) can detect individually 28 HPV genotypes. We assessed the agreement between linear array HPV genotyping (LA-HPV) and HPV-28 for detection of 27 HPV genotypes in 410 stored anogenital samples (75 anal samples, 335 physician-collected cervical samples) collected over 5 years from 410 individuals (13 men, 397 women), including 202 HIV-seropositive individuals. HPV DNA was detected in 393 (95.9%, 95% confidence interval [CI]: 93.4-97.4) and 382 (93.2%, 95% CI: 90.3-95.3) samples with HPV-28 and LA-HPV (p = 0.13), respectively, for a good agreement of 96.3% (κ = 0.65). Of the 10503 HPV typing results, 10195 (780 positive, 9577 negative) were concordant, for an agreement of 97.1% (95% CI: 96.7-97.4) and an excellent of κ = 0.82 (95% CI: 0.80-0.84). The mean type-specific concordance for 27 genotypes was 97.0%, 95% CI: 95.8-98.5 (κ = 0.86 ± 0.07, 95% CI: 0.83-0.88). Excellent agreement was obtained individually for all high-risk genotypes (κ = 0.81-0.97) and for most other genotypes except for types 42, 44, 54, 68, and 69. The mean number of types per sample in discordant samples detected with LA-HPV (3.0, 95% CI: 2.7-3.4) was greater than in concordant samples (1.4, 95% CI: 1.3-1.5; p< 0.001). In conclusion, HPV-28 compared favorably with LA-HPV, but was more frequently positive for HPV42 and HPV68.

Double lung transplantation in an HIV-positive patient with Mycobacterium kansasii infection.

Good outcomes with kidney and liver transplantation in HIV-positive patients have led clinicians to recommend lung transplantation in HIV-positive patients based on extrapolated data. Pre-transplant mycobacterial infection is associated with an increased risk of developing new infection or aggravating existing infection, though it does not contraindicate transplantation in non-HIV-infected patients. However, no data exists regarding the outcome of HIV-positive patients with pre-transplant mycobacterial infection. We report a case of double lung transplantation in a 50-year-old HIV-positive patient with alpha-1 antitrypsin deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one sputum culture and the patient was considered merely colonized as no clinical evidence of pulmonary or disseminated disease was present. The patient successfully underwent a double lung transplantation. Nontuberculous mycobacterial infection was diagnosed histologically on examination of native lungs. Surveillance and watchful waiting were chosen over treatment of the infection. HIV remained under control post-transplantation with no AIDS-defining illnesses throughout the follow-up. A minimal acute rejection that responded to increased corticosteroids was reported. At 12 months post-transplant, a bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence of isolation nor recurrence of nontuberculous mycobacteria was reported post-transplantation. At 15 months post-transplant, the patient remained stable with an FEV1 of 30%. The presence of pre-transplant nontuberculous mycobacterial infection did not translate into recurrence of nontuberculous mycobacterial infection post-transplant. Whether it contributed to bronchiolitis obliterans syndrome remains unknown.

Cocaine/crack use is not associated with fibrosis progression measured by AST-to-Platelet Ratio Index in HIV-HCV co-infected patients: a cohort study.

BACKGROUND: Cocaine and crack use has been associated with HIV and HCV infections, but its consequences on HCV progression have not been well established. We analyzed the impact of cocaine/crack use on liver fibrosis progression in a cohort of HIV-HCV co-infected patients. METHODS: A Canadian multicenter prospective cohort study followed 1238 HIV-HCV co-infected persons every 6 months between 2003 and 2013. Data were analyzed from 573 patients with positive HCV RNA, not on HCV treatment, without significant liver fibrosis (AST-to-Platelet Ratio Index (APRI) <1.5) or history of end-stage liver disease at baseline, and having at least two study visits. Recent cocaine/crack use was defined as use within 6 months of cohort entry. Incidence rates of progression to significant fibrosis (APRI ≥ 1.5) were determined according to recent cocaine/crack use. Cox Proportional Hazards models were used to assess the association between time-updated cocaine/crack use and progression to APRI ≥ 1.5 adjusting for age, sex, HCV duration, baseline ln(APRI), and time-updated alcohol abuse, history of other drug use and CD4+ cell count. RESULTS: At baseline, 211 persons (37%) were recent cocaine/crack users and 501 (87%) ever used cocaine/crack. Recent users did not differ from non-recent users on gender, age, and CD4+ T-cell count. Over 1599 person-years of follow up (522 PY in recent users, 887 PY in previous users and 190 PY in never users),158 (28%) persons developed significant fibrosis (9.9/100 PY; 95% CI, 8.3-11.4); 56 (27%) recent users (10.7/100 PY; 7.9-13.5), 81 (28%) previous users (9.1/100 PY; 7.1-11.1), and 21 (29%) never users (11.1/100 PY; 6.3-15.8). There was no association between ever having used or time-updated cocaine/crack use and progression to APRI ≥ 1.5 (adjusted HR (95%CI): 0.96 (0.58, 1.57) and 0.88;(0.63-1.25), respectively). CONCLUSIONS: We could not find evidence that cocaine/crack use is associated with progression to advanced liver fibrosis in our prospective study of HIV-HCV co-infected patients.

Epidemiology and outcome of antimicrobial resistance to gram-negative pathogens in bacteriuric kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, episodes of bacteriuria are often treated regardless of the presence of symptoms because of the lack of clear treatment guidelines suggesting otherwise. This practice may lead to the development of antimicrobial resistance. Our aim was to determine the incidence, determinants, and impact of antimicrobial resistance in kidney transplant recipients with gram-negative bacteriuria. METHOD: We conducted a single-center, retrospective cohort study in patients who underwent kidney transplantation between January 2008 and June 2013. To identify risk factors for the development of resistance, we used a logistic regression model with generalized estimating equations to account for within-subject correlation. RESULTS: Among the 318 patients who underwent kidney transplantation during the study period, 147 patients developed 555 gram-negative episodes of bacteriuria. Resistance to trimethoprim-sulfamethoxazole and quinolones, and production of extended-spectrum ß-lactamase (ESBL) occurred in 52%, 21%, and 5% of isolated microorganisms, respectively. An increased risk of resistance to quinolones and production of ESBL were associated with concomitant diabetes (odds ratio [OR]: 2.29, 95% confidence interval [CI]: 1.11-4.74), the first year post transplantation (OR: 2.88, 95% CI: 1.36-6.09), and antibiotic treatment in the previous 6 months (OR: 3.36, 95% CI: 1.66-6.81). This resistance profile was also associated with the presence of symptoms, a longer duration of antibiotic treatment, and a higher rate of hospitalization. CONCLUSION: Antimicrobial resistance to quinolones and production of ESBL were commonly seen, and were shown to demonstrate an adverse impact on outcomes in kidney transplant recipients with gram-negative bacteriuria. The decision on treatment for asymptomatic bacteriuria should be made with caution, given the potential for the selection of resistant strains.

Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons.

BACKGROUND: Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). METHODS: Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. RESULTS: A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%). CONCLUSIONS: Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.

How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?

BACKGROUND: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)-HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials. METHODS: Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOTON-1 (NCT01667731), TURQUOISE-I (NCT01939197), ION-4 (NCT02073656), and ALLY-2 (NCT02032888) that evaluated simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir/dasabuvir; sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir, respectively, to the Canadian Coinfection Cohort, representing approximately 23% of the total coinfected population in care in Canada. RESULTS: Of 874 active participants, 70% had chronic HCV, of whom 410, 26, 94, and 11 had genotypes 1, 2, 3, and 4, respectively. After applying trial eligibility criteria, only 5.9% (24/410) would have been eligible for enrollment in the simeprevir trial, 9.8% (52/530) in PHOTON-1, 6.3% (26/410) in TURQUOISE-I, and 8.1% (34/421) in ION-4. The ALLY-2 study was more inclusive; 43% (233/541) of the cohort would have been eligible. The most exclusive eligibility criteria across all trials with the exception of ALLY-2 were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%). CONCLUSIONS: DAA trial results may have limited generalizability, since the majority of coinfected individuals were not eligible to participate. Exclusions appeared to be related to improving treatment outcomes by not including those at higher risk of poor adherence and reinfection--individuals for whom real-world data are urgently needed.

Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males.

BACKGROUND: Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men. METHODS: We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status. RESULTS: In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001). CONCLUSIONS: Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; ClinicalTrials.gov number, NCT00090285.).

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review.

The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods: We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results: Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions: Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.

Factors and Priorities Influencing Satisfaction with Care among Women Living with HIV in Canada: A Fuzzy Cognitive Mapping Study.

Engagement along the HIV care cascade in Canada is lower among women compared to men. We used Fuzzy Cognitive Mapping (FCM), a participatory research method, to identify factors influencing satisfaction with HIV care, their causal pathways, and relative importance from the perspective of women living with HIV. Building from a map of factors derived from a mixed-studies review of the literature, 23 women living with HIV in Canada elaborated ten categories influencing their satisfaction with HIV care. The most central and influential category was "feeling safe and supported by clinics and healthcare providers", followed by "accessible and coordinated services" and "healthcare provider expertise". Participants identified factors that captured gendered social and health considerations not previously specified in the literature. These categories included "healthcare that considers women's unique care needs and social contexts", "gynecologic and pregnancy care", and "family and partners included in care." The findings contribute to our understanding of how gender shapes care needs and priorities among women living with HIV.

Prevalence of Physical Health, Mental Health, and Disability Comorbidities among Women Living with HIV in Canada.

Life expectancy for people living with HIV has increased, but management of HIV is now more complex due to comorbidities. This study aimed to measure the prevalence of comorbidities among women living with HIV in Canada. We conducted a cross-sectional analysis using data from the 18-months survey (2014−2016) of the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Self-report of diagnosed conditions was used to measure lifetime prevalence of chronic physical conditions, current mental health conditions, and disabilities. We examined frequency of overlapping conditions and prevalence stratified by gender identity, ethnicity, and age. Among 1039 participants, 70.1% reported a physical health diagnosis, 57.4% reported a current mental health diagnosis, 19.9% reported a disability, and 47.1% reported both physical and mental health comorbidities. The most prevalent comorbidities were depression (32.3%), anxiety (29.5%), obesity (26.7%, defined as body mass index >30 kg/m2), asthma/chronic obstructive pulmonary disease (23.3%), sleep disorder (22.0%), drug addiction (21.9%), and arthritis/osteoarthritis (20.9%). These results highlight the complexity of HIV care and the important prevalence of comorbidities. Personalized health care that integrates care and prevention of all comorbidities with HIV, with attention to social determinants of health, is necessary to optimize health and well-being of women living with HIV.

HAART and progression to high-grade anal intraepithelial neoplasia in men who have sex with men and are infected with HIV.

BACKGROUND: Human immunodeficiency virus (HIV)-seropositive men who have sex with men (MSM) are at risk for anal intraepithelial neoplasia (AIN) and cancer. The goal of this study was to identify risk factors associated with high-grade AIN (AIN-2,3) in HIV-positive MSM, including the receipt of highly active antiretroviral therapy (HAART). METHODS: A cohort study involving 247 HIV-seropositive MSM receiving HAART or initiating HAART was followed up every 6 months for 3 years with human papillomavirus (HPV) testing and high-resolution anoscopy to identify predictors of AIN-2,3 by Cox regression analysis and period prevalence logistic regression. RESULTS: AIN-2,3 was observed during the study in 132 (53%) of 247 participants. The progression rate to AIN-2,3 from a lesser abnormality at baseline was 12.8 cases per 1000 person-months (95% confidence interval [CI], 9.8-16.5 cases per 1000 person-months). The risk of AIN-2,3 increased with age (odds ratio [OR], 3.09 [95% CI, 1.12-8.52] for men 40-49 years of age and 4.78 [95% CI, 1.29-17.73] for men >50 years of age, compared with men <40 years of age) and for men whose CD4+ cell counts were <50 cells/mm(3) before starting HAART (OR, 14.40 [95% CI, 1.45-143.58]). Men who had been receiving their current HAART regimen for >4 years had a marginally significant lower risk of AIN-2,3 after adjustment for HPV (OR, 0.28 [95% CI, 0.07-1.06]) compared with those treated for <4 years. Anal HPV type 16 (HPV16) or type 18 (HPV18) infections (OR, 14.18; [95% CI, 3.51-57.32]) and HPV16 and HPV18 co-infection (OR, 31.03 [ 95% CI, 5.68-169.60]) were strongly associated with progression to AIN-2,3. CONCLUSION: HPV16 and HPV18 infections and a low nadir CD4+ cell count increase the risk of AIN-2,3. Receiving the same HAART regimen for >4 years may contribute some benefit against AIN-2,3.

Discussing reproductive goals with healthcare providers among women living with HIV in Canada: the role of provider gender and patient comfort.

Antiretroviral therapy effectively prevents sexual and vertical transmission of HIV. Yet, some women living with HIV report having unmet needs for reproductive health care. This study measured the prevalence of women discussing reproductive goals with any current healthcare provider and assessed the effect of the current HIV care provider's gender on such discussions and whether comfort was a mediator. We analysed baseline and 18-month survey data from 533 women living with HIV enrolled in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) (2013-2017), a community-based participatory study, restricting the analysis to participants aged 16-45 years. We used causal mediation analysis to estimate direct and indirect effects of the gender of one's HIV care provider on reproductive discussions, incorporating mediating and interaction effects of women having any provider with whom they felt comfortable discussing reproductive goals. Between the baseline and 18-month follow-up surveys, 34.3% (183/533) of women discussed their reproductive goals with a healthcare provider. Having a woman HIV care provider was associated with a 1.18 excess relative risk (ERR) of discussion (95%CI: 0.15, 2.20). The mediating effect of comfort was primarily explained by the fact that those participants with women providers felt more comfortable discussing their reproductive goals compared to participants with men providers, accounting for 66% (95%CI: 32%, 99%) of the total effect. Findings support that HIV provider gender affects women's comfort and whether they discuss reproductive goals, which must be acknowledged and addressed in care delivery.

Performance of an agar dilution method and a Vitek 2 card for detection of inducible clindamycin resistance in Staphylococcus spp.

The D-zone test detects inducible clindamycin resistance in Staphylococcus spp. Two other methods not described by the Clinical and Laboratory Standards Institute (CLSI) are available to test for this resistance mechanism: an agar dilution method and new Vitek 2 cards. This study evaluated the performance of both methods in detecting inducible clindamycin resistance. Nonduplicate clinical strains of Staphylococcus spp. (111 Staphylococcus aureus and 52 coagulase-negative staphylococcus strains), intermediate or resistant to erythromycin but susceptible to clindamycin, were obtained from three hospitals in Montreal, Quebec, Canada. Molecular analysis to detect resistance genes was conducted on all strains. A Mueller-Hinton agar containing 1 mg of erythromycin and 0.5 mg of clindamycin/liter was used for the dilution method, and two inocula were tested: 10(4) and 10(5) CFU per spot. Plates were read at 24 and 48 h. The Vitek 2 AST-P580 card was used according to the manufacturer's recommendations. The results were compared to those of the D-zone test. The D-zone test was positive in 134 of 163 (82%) strains. With the 10(4) CFU inoculum, the sensitivities were 84 and 99% at 24 and 48 h, respectively. The 10(5) CFU inoculum increased the sensitivities at 24 and 48 h to 91 and 100%, respectively. The specificity was 100% for the 10(4) CFU inoculum at 24 h and 97% for the other combinations. The sensitivity and specificity for the Vitek 2 card were 93 and 100%, respectively. The performance of both the agar dilution method and the Vitek 2 card was good, but these methods were not as sensitive as the D-zone test at 24 h.

Polyfunctional Fc Dependent Activity of Antibodies to Native Trimeric Envelope in HIV Elite Controllers.

Antibody dependent (AD) functions such as AD cellular cytotoxicity (ADCC) were associated with lower viral load (VL) in untreated HIV progressors and protection from HIV infection in the modestly protective RV144 HIV vaccine trial. Target cells used to measure ADCC, AD complement deposition (ADCD), and AD cellular trogocytosis (ADCT) have been either HIV envelope (Env) gp120-coated CEM.NKr.CCR5 cells or HIV infected cell cultures. In HIV infected cell cultures, uninfected bystander cells take up gp120 shed from infected cells. Both gp120-coated and gp120+ bystander cells expose CD4 induced (CD4i) epitopes, which are normally hidden in native trimeric Env expressed by genuinely HIV infected cells since Nef and Vpu downmodulate cell surface CD4. Antibody dependent assays using either of these target cells probe for CD4i Abs that are abundant in HIV+ plasma but that do not recognize HIV-infected cells. Here, we examined ADCC, ADCD, and ADCT functions using a target cell line, sorted HIV-infected cell line cells, whose HIV infection frequency nears 100% and that expresses HIV Env in a native trimeric closed conformation. Using sorted HIV-infected cells (siCEM) as targets, we probed the binding and AD functions of anti-gp120/Env Abs in plasma from HIV-infected untreated progressor (UTP, n = 18) and treated (TP, n = 24) subjects, compared to that in Elite controllers (EC, n = 37) and Viral Controllers (VC, n = 16), which are rare subsets of HIV-infected individuals who maintain undetectable or low VL, respectively, without treatment. Gp120-coated beads were used to measure AD cellular phagocytosis. Equivalent concentrations of input IgG in plasma from UTPs, ECs, and VCs supported higher levels of all AD functions tested than plasma from TPs. When AD activities were normalized to the concentration of anti-gp120/Env-specific Abs, between-group differences largely disappeared. This finding suggests that the anti-gp120/Env Abs concentrations and not their potency determined AD functional levels in these assays. Elite controllers did differ from the other groups by having AD functions that were highly polyfunctional and highly correlated with each other. PCR measurement of HIV reservoir size showed that ADCC activity was higher in ECs and VCs with a reservoir size below the limit of detection compared to those having a measurable HIV reservoir size.

HIV Gag p24 specific responses secreting IFN-gamma and/or IL-2 in treatment-naïve individuals in acute infection early disease (AIED) are associated with low viral load.

HIV-specific immune responses in acute infection early disease (AIED) may be effective at controlling viral replication and in establishing viral load (VL) set point. However, evidence correlating the function and specificity of these responses with the VL set point is lacking. To address this issue, we screened cells from 59 treatment-naïve HIV infected individuals (33 in AIED and 26 progressors) for responses to the entire HIV proteome using a dual color ELISPOT assay detecting 3 functional lymphocyte populations: single IFN-gamma, dual IFN-gamma/IL-2 and single IL-2 secreting cells. Responses characterized by dual secreting cells contributed more to the HIV specific response in AIED versus chronic infection. Of responses directed to individual HIV gene products the magnitude and breadth of only Gag p24-specific responses for the 3 functional subsets were associated with lower concurrent or set point VL. Therefore the early appearance of broader and more intense Gag-p24-specific responses may be a determinant of subsequent VL.

Bacterial sacroiliitis and gluteal abscess after dilation and curettage for incomplete abortion.

BACKGROUND: Pyogenic infection with Streptococcus agalactiae is a potentially life-threatening disease associated with significant morbidity and mortality. This type of infection has seldom been reported as a complication of dilation and curettage after an incomplete abortion. CASE: A young woman presented to the emergency department with rapidly progressive left-sided lower back pain, general malaise, and chills evolving over the previous 48-hours after dilation and curettage for incomplete abortion. Streptococcus agalactiae was isolated in the blood. The patient developed pelvic osteomyelitis despite aggressive medical therapy and required prolonged treatment before significant clinical improvement was noted. CONCLUSION: Although very rare, serious pyogenic complications of dilation and curettage after incomplete abortion do occur and may present a diagnostic challenge.

[Treatment of HIV marginalized patients: an approach to documenting medical and psychosocial appointments of patients with problematic drug use]. / Traitement du VIH auprès d'une clientèle marginalisée: approche de proximité pour favoriser l'observance des rendez-vous.

OBJECTIVE: To document compliance with medical and psychosocial appointments for HIV/AIDS treatment in a population of marginalized individuals with problematic drug use. METHOD: This is a retrospective study exploring appointment compliance for an HIV treatment based on an outreach intervention. Information regarding the medical and psychosocial appointments of 185 patients of the HIV-Drug Addiction outpatient unit, at the University of Montreal Hospital Centre (CHUM), has been collected for a one-year period (2006-2007). The compliance rate of appointments has been calculated according to the type of care provided: 1) conventional, provided only in the clinic at the "fixed" location, and 2) outreach-based, when the team at the fixed location is complemented by the intervention of a "mobile" team for the more unstable patients. RESULTS: Compliance rates for medical and psychosocial appointments in patients receiving care solely at the fixed location is 61.4%. For those whom care is received at the fixed location while complemented by the mobile team, the corresponding rate is 73.9%. This is an elevated compliance rate, higher than those generally reported for outreach-based programs. CONCLUSION: These results lend support to the success of programs integrating an outreach-based intervention for a vulnerable clientele. Indeed, appointment compliance in those who are more disorganized, for which the mobile team has intervened, has proven comparable and even superior to compliance with appointments when treatment is only received at the fixed location.

Measuring the impact of an HIV rotation on trainees' knowledge and confidence level: The importance of inviting recent graduates.

Background: The new Canadian Residency Accreditation Consortium (CanRAC) standards recommend surveying recently graduated trainees to target improvements in training programs. The goal of this study was to estimate the impact of a rotation in an HIV clinic on trainees' related knowledge, confidence, and practice profile at the Université de Montréal. Methods: An electronic survey was sent to practising physicians who completed the rotation between 2006 and 2016. Participants were asked to rate their agreement and level of confidence toward HIV- and HCV-related topics using 5-point Likert scales (0 to 4). Descriptive statistics and mean comparisons were calculated. Results: Among invited participants, 27 of 45 (60%) completed the questionnaire. The majority of respondents were infectious diseases physicians (48%) or family physicians (37%) and had an outpatient caseload of <10 HIV patients/year (80%). For 37% of the respondents, the rotation had a large or very large impact on their career path. They considered that the rotation had increased their knowledge on the overall management of HIV (mean 3.2/4 [95% CI 2.9 to 3.4]), but less on pre-exposure prophylaxis (PrEP) (mean 1.5/4 [95% CI 1.1 to 2.0]) or HCV care (mean 1.9/4 [95% CI 1.4 to 2.3]). Participants felt less confident with genotyping interpretation (mean 2.6/4 [95% CI 2.2 to 2.9]) and PrEP (mean 2.4/4 [95% CI 2.0 to 2.8]). Conclusions: These results suggest that a rotation in an HIV clinic improves knowledge related to HIV care. Feedback from past graduates helped us identify gaps in knowledge or level of confidence in PrEP and HCV care, which will feed curriculum improvement.

Historique: Selon les normes du nouveau Consortium canadien d'agrément des programmes de résidence (CanRAC), il est recommandé de sonder les récents diplômés pour améliorer les programmes de formation. La présente étude visait à estimer les répercussions d'une rotation dans une clinique de VIH sur les connaissances, la confiance et le profil d'exercice des stagiaires de l'Université de Montréal. Méthodologie: Les médecins en exercice qui ont effectué la rotation entre 2006 et 2016 ont reçu un sondage en ligne. Les participants ont été invités à classer leur accord et leur niveau de confiance à l'égard des sujets reliés au VIH et au VHC à l'aide d'échelles de Likert en cinq points (de 0 à 4). Les chercheurs ont établi des statistiques descriptives et des comparaisons de moyennes. Résultats: Chez les participants invités, 27 sur 45 (60 %) ont rempli le questionnaire. La majorité des répondants étaient des infectiologues (48 %) et des médecins de famille (37 %) qui soignaient une cohorte de moins de dix patients ambulatoires atteints du VIH par année (80 %). Pour 37 % des répondants, la rotation a eu des répercussions importantes ou très importantes sur leur cheminement de carrière. Selon eux, la rotation avait accru leurs connaissances sur la prise en charge globale du VIH (moyenne de 3,2/4 [IC à 95 %, 2,9 à 3,4]), mais pas autant sur la prophylaxie préexposition (PrPE) (moyenne de 1,5/4 [IC à 95 %, 1,1 à 2,0]) ou les soins du VHC (moyenne de 1,9/4 [IC à 95 %, 1,4 à 2,3]). Les participants se sentaient moins à l'aise pour interpréter le génotypage (moyenne de 2,6/4 [IC à 95 %, 2,2 à 2,9]) et la PrPE (moyenne de 2,4/4 [IC à 95 %, 2,0 à 2,8]). Conclusions: D'après ces résultats, une rotation dans une clinique de VIH améliore les connaissances sur les soins du VIH. Les commentaires d'anciens diplômés ont contribué à déterminer des lacunes en matière de connaissances ou de confiance sur la PrPE et les soins du VHC, ce qui sera utile pour améliorer le programme.