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Background People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine. Methods This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses of TCZ or matching placebo intravenously. Following a 10-week treatment period and a 12-week washout, participants were switched to the opposite treatment. The primary endpoints were safety and posttreatment levels of C-reactive protein (CRP) and CD4+ T-cell cycling. Secondary endpoints included changes in inflammatory indices and lipid levels. Results There were 9 treatment-related toxicities of grade 2 or greater during TCZ administration (mostly neutropenia) and 2 during placebo administration. Thirty-one of 34 participants completed the study and were included in a modified intent-to-treat analysis. TCZ reduced levels of CRP (median decrease, 1819.9 ng/mL, P < .0001; effect size, 0.87) and reduced inflammatory markers in PWH, including D-dimer, soluble CD14, and tumor necrosis factor receptors. T-cell cycling tended to decrease in all maturation subsets after TCZ administration, but was only significant among naive CD4 T cells. Lipid levels, including lipid classes that have been related to cardiovascular disease risk, increased during TCZ treatment. Conclusions TCZ is safe and decreases inflammation in PWH; IL-6 is a key driver of the inflammatory environment that predicts morbidity and mortality in ART-treated PWH. The clinical significance of lipid elevations during TCZ treatment requires further study.

Background Long COVID is a heterogenous condition. We previously demonstrated distinct phenotypes of long COVID, but the impact of later waves caused by SARS-CoV-2 variants on long COVID presentations has not been described. Methods We selected individuals with ongoing symptoms > 4 weeks from PCR-confirmed COVID-19 in a multicentre, prospective cohort study. We used multiple correspondence analysis and hierarchical clustering on self-reported symptoms to identify symptom clusters, in individuals recruited during two periods; cohort 1 from March 2020 to April 2021, and cohort 2 from April 2021 to March 2022. We explored differences in symptoms by mapping acute infection to one of four COVID-19 waves in Ireland (table 1) as well as vaccination status, and used Chi2 test to compare symptoms frequencies. Results Demographics are shown in Table 2. Cluster analysis of each cohort demonstrated 3 distinct clusters in both cohorts, which shared similar clinical characteristics; a musculoskeletal/pain symptom cluster, a cardiorespiratory cluster and a third less symptomatic cluster (Figure 1). While symptoms within clusters were similar across both periods, in the cardiorespiratory cluster, the frequency of palpitations decreased (56% vs 16%) and cough increased (14% vs 45%) between reporting periods (both P< 0.01). Furthermore, a greater proportion of palpitations were reported in those with COVID-19 from waves 1 and 2 (35% and 28%) compared to 3 and 4 (both 12%, P< 0.001), and a greater proportion of chest pain in waves 1, 2 and 4 compared to wave 3. There were no differences in other symptoms (Table 3). Additionally there were significantly less palpitations reported in those vaccinated at the time of review (17% vs 31% P=0.002), but not chest pain (30% vs 39% P=0.13). In multivariate analysis, infection in wave 3 and 4 but not vaccination status remained significantly associated with lower reported palpitations (OR (95% CI) 0.28 (0.13–0.97) and 0.5 (0.06–0.87) for waves 3 and 4, both P< 0.05), and wave 3 infection remained independently associated with lower reported chest pain (OR 0.3 (0.25–0.7)). Conclusion Three symptom clusters define long COVID across the two cohorts, but characteristics of the cardiorespiratory phenotype have evolved over time with evolution of SARS-CoV-2 variants. Disclosures All Authors: No reported disclosures.

Background Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection. Methods In a multicentre prospective cohort, adult subjects provided samples before and 14 days (d14) post 3rd dose vaccine with Pfizer-BioNTech 162b2. At 18-22 weeks post vaccine, subjects self-reported SARS-CoV-2 infection (confirmed by PCR or antigen test). We used electrochemiluminescence assays to quantify antibodies to SARS-CoV-2 spike subunit 1 (S1), subunit 2 (S2) and receptor-binding domain (RBD) in plasma (reported in WHO IU/mL). In a subset of subjects, we assessed SARS-CoV-2 specific differentiated B-cell (plasma cell) and memory B-cell responses from peripheral blood mononuclear cells. Unstimulated plasma cells, and memory B cells stimulated with R848 and IL2, were seeded on plates coated with RBD or full Spike antigen and antigen-specific responses measured by ELISpot (Mabtech ELISpot, Sweden). We compared between group differences by Wilcoxon signed rank or Mann–Whitney tests. Data are median [IQR] unless specified. Results Of 133 subjects (age 43 [32-50], 81.2% female (table 1), 77 subjects in the B-cell subgroup (table 2)), 47 (35.3%) reported SARS-CoV-2 infection post 3rd vaccine. Antibody titres, plasma cell and memory B-cell responses all increased significantly at d14 post 3rd vaccine (Table 1 & 2, all P< 0.001). Although d14 antibody titres did not differ in those with and without subsequent infection (table 1), those reporting subsequent infection had significantly lower d14 RBD-specific plasma cells and a lower proportion of RBD-specific memory B-cells (Figure 1a-b, both P< 0.05). Similar results were observed with full-spike-specific memory B-cell responses (Figure 1d). The differences persisted when the non-infected group was restricted only to those reporting a confirmed close contact (n=26). Conclusion Infection following 3rd dose vaccine is associated with lower d14 circulating and memory B cell responses, but not antibody titres, suggesting B-cell responses better predict protection against subsequent SARS-CoV-2 infection. Disclosures All Authors: No reported disclosures.

Summary In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Background Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Methods Among 606 women with HIV in the Women’s Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28–), exhaustion (%PD-1+), and nonactivation/normal function (%CD57–CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. Results At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Conclusions Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

Background Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. Methods In 350 women with HIV from the Women’s Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years. Results Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (β = 161.89 ng/mL; 95% confidence interval [CI], 18.37–305.41 and 65.48 ng/mL, 95% CI, 6.64–124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63–484.79; P = .04), but not in premenopausal or postmenopausal periods. Conclusions In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.

Background Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. Methods In 241 women participating in the Women’s Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28−), exhaustion (%PD-1+), and co-stimulation (%CD57− CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors. Results At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P 40 copies/mL and CD4 Conclusions Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non–AIDS-related disease risk in this population.

BackgroundAlthough cell surface immune checkpoint proteins (ICPs) such as PD-1 expressed on T cells are associated with T-cell exhaustion, HIV disease progression, and AIDS events, they have shown limited utility in predicting non-AIDS morbidity. Given that ICPs also exist in soluble forms and are elevated in ART-treated HIV infection, we tested the hypothesis that soluble ICPs may be predictive of non-AIDS events in adults initiating ART.MethodsUtilizing a nested case–control study from the AIDS Clinical Trials Group ALLRT cohort, we measured plasma levels of 15 soluble inhibitory and activating ICPs by Luminex. Participants (134 cases, 292 matched controls) were evaluated pre-ART, a year post-ART, and immediately preceding a non-AIDS event, which included myocardial infarction (MI)/stroke, malignancy, serious bacterial infection, and nonaccidental death.ResultsConditional logistic regression analysis determined that higher levels of soluble CD27 were associated with increased risk of non-AIDS events at all time points. Higher levels of CD40 at baseline and pre-event and CD80 at pre-event were associated with increased risk of non-AIDS events. Examining specific non-AIDS events, multiple ICPs were associated with malignancy at baseline and pre-event, whereas only higher CD27 levels were associated with increased risk of MI/stroke at year 1 and pre-event.ConclusionsWhile select soluble ICPs were associated with non-AIDS events, CD27 emerged as a consistent marker irrespective of ART. Our data may offer guidance on new targets for early clinical monitoring in people with HIV who remain at greater risk of specific non-AIDS events.

Background Patients with malignant gliomas have a poor prognosis. However, little is known about patients’ and caregivers’ understanding of the prognosis and the primary treatment goal. Methods We conducted a prospective study in patients with newly diagnosed malignant gliomas (N = 72) and their caregivers (N = 55). At 12 weeks after diagnosis, we administered the Prognosis and Treatment Perceptions Questionnaire to assess understanding of prognosis and the Hospital Anxiety and Depression Scale to evaluate mood. We used multivariable regression analyses to explore associations between prognostic understanding and mood and McNemar tests to compare prognostic perceptions among patient-caregiver dyads (N = 48). Results A total of 87.1% (61/70) of patients and 79.6% (43/54) of caregivers reported that it was “very” or “extremely” important to know about the patient’s prognosis. The majority of patients (72.7%, [48/66]) reported that their cancer was curable. Patients who reported that their illness was incurable had greater depressive symptoms (B = 3.01, 95% CI, 0.89-5.14, P = .01). There was no association between caregivers’ prognostic understanding and mood. Among patient-caregiver dyads, patients were more likely than caregivers to report that their primary treatment goal was cure (43.8% [21/48] vs 25.0% [12/48], P = .04) and that the oncologist’s primary goal was cure (29.2% [14/48] vs 8.3% [4/48], P = .02). Conclusions Patients with malignant gliomas frequently hold inaccurate perceptions of the prognosis and treatment goal. Although caregivers more often report an accurate assessment of these metrics, many still report an overly optimistic perception of prognosis. Interventions are needed to enhance prognostic communication and to help patients cope with the associated distress.

Background Alterations in gut microbiota (GMB) and host metabolites have been noted in individuals with HIV. However, it remains unclear whether alterations in GMB and related functional groups contribute to disrupted host metabolite profiles in these individuals. Methods This study included 185 women (128 with longstanding HIV infection, 88% under antiretroviral therapy; and 57 women without HIV from the same geographic location with comparable characteristics). Stool samples were analyzed by 16S rRNA V4 region sequencing, and GMB function was inferred by PICRUSt. Plasma metabolomic profiling was performed using liquid chromatography–tandem mass spectrometry, and 133 metabolites (amino acids, biogenic amines, acylcarnitines, and lipids) were analyzed. Results Four predominant bacterial genera were identified as associated with HIV infection, with higher abundances of Ruminococcus and Oscillospira and lower abundances of Bifidobacterium and Collinsella in women with HIV than in those without. Women with HIV showed a distinct plasma metabolite profile, which featured elevated glycerophospholipid levels compared with those without HIV. Functional analyses also indicated that GMB lipid metabolism was enriched in women with HIV. Ruminococcus and Oscillospira were among the top bacterial genera contributing to the GMB glycerophospholipid metabolism pathway and showed positive correlations with host plasma glycerophospholipid levels. One bacterial functional capacity in the acetate and propionate biosynthesis pathway was identified to be mainly contributed by Bifidobacterium; this functional capacity was lower in women with HIV than in women without HIV. Conclusions Our integrative analyses identified altered GMB with related functional capacities that might be associated with disrupted plasma metabolite profiles in women with HIV.

Background Despite low plasma human immunodeficiency virus (HIV) RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, immune activation, and quality of life (QoL). Methods A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naive HIV controllers (N = 35), defined as having HIV RNA Results Before ART, HIV controllers with undetectable residual viremia Conclusions ART in HIV controllers reduces T-cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.

BackgroundWhether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals.MethodsWe conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata.ResultsTwenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW.ConclusionsOur study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.

AimsTo test whether human immunodeficiency virus (HIV) infection and subclinical cardiovascular disease (sCVD) are associated with expression of CXCR4 and other surface markers on classical, intermediate, and non-classical monocytes in women.Methods and resultssCVD was defined as presence of atherosclerotic lesions in the carotid artery in 92 participants of the Women’s Interagency HIV Study (WIHS). Participants were stratified into four sets (n = 23 each) by HIV and sCVD status (HIV−/sCVD−, HIV−/sCVD+, HIV+/sCVD−, and HIV+/sCVD+) matched by age, race/ethnicity, and smoking status. Three subsets of monocytes were determined from archived peripheral blood mononuclear cells. Flow cytometry was used to count and phenotype surface markers. We tested for differences by HIV and sCVD status accounting for multiple comparisons. We found no differences in monocyte subset size among the four groups. Expression of seven surface markers differed significantly across the three monocyte subsets. CXCR4 expression [median fluorescence intensity (MFI)] in non-classical monocytes was highest among HIV−/CVD− [628, interquartile range (IQR) (295–1389)], followed by HIV+/CVD− [486, IQR (248–699)], HIV−/CVD+ (398, IQR (89–901)), and lowest in HIV+/CVD+ women [226, IQR (73–519)), P = 0.006 in ANOVA. After accounting for multiple comparison (Tukey) the difference between HIV−/CVD− vs. HIV+/CVD+ remained significant with P = 0.005 (HIV−/CVD− vs. HIV+/CVD− P = 0.04, HIV−/CVD− vs. HIV−/CVD+ P = 0.06, HIV+/CVD+ vs. HIV+/CVD− P = 0.88, HIV+/CVD+ vs. HIV−/CVD+ P = 0.81, HIV+/CVD− vs. HIV−/CVD+, P = 0.99). All pairwise comparisons with HIV−/CVD− were individually significant (P = 0.050 vs. HIV−/CVD+, P = 0.028 vs. HIV+/CVD−, P = 0.009 vs. HIV+/CVD+). CXCR4 expression on non-classical monocytes was significantly higher in CVD− (501.5, IQR (249.5–887.3)) vs. CVD+ (297, IQR (81.75–626.8) individuals (P = 0.028, n = 46 per group). CXCR4 expression on non-classical monocytes significantly correlated with cardiovascular and HIV−related risk factors including systolic blood pressure, platelet and T cell counts along with duration of antiretroviral therapy (P ConclusionCXCR4 expression in non-classical monocytes was significantly lower among women with both HIV infection and sCVD, suggesting a potential atheroprotective role of CXCR4 in non-classical monocytes.

We examined associations of 5 plasma choline metabolites with carotid plaque among 520 HIV-infected and 217 HIV-uninfected participants (112 incident plaque cases) over 7 years. After multivariable adjustment, higher gut microbiota-related metabolite trimethylamine-N-oxide (TMAO) was associated with an increased risk of carotid plaque in HIV-infected participants (risk ratio = 1.25 per standard deviation increment; 95% confidence interval, 1.05-1.50; P = .01). TMAO was positively correlated with biomarkers of monocyte activation and inflammation (sCD14, sCD163). Further adjustment for these biomarkers attenuated the association between TMAO and carotid plaque (P = .08). Among HIV-infected individuals, plasma TMAO was associated with carotid atherosclerosis progression, partially through immune activation and inflammation.

Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery.

Several lines of evidence support the concept that NK cells play an important role in control of hepatitis C virus (HCV) infection via cytokine secretion and cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development, activation, proliferation, and cytokine secretion. The IL-7Rα chain [cluster of differentiation (CD)127] is expressed on NK cells, with greatest abundance on the CD56brightCD16dim/− (CD56bright) subset. Here, we measured CD127 expression on CD56bright, CD56dimCD16+ (CD56dim), or CD56negCD16+ (CD56neg) NK cell subsets of 25 uninfected donors (UD); 34 chronic HCV-infected, treatment-naiüve; 25 HIV-infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV–HIV-coinfected subjects on ART. Interestingly, CD127 expression on CD56bright NK cells negatively correlated with HCV plasma levels in HCV monoinfection and HCV–HIV coinfection. IL-7 induced CD69 expression, as well as IFN-γ production, in CD56bright NK cells and also enhanced the IFN-α-induced CD69 expression on these cells. The latter was impaired in HIV infection. Furthermore, IL-7 induced B cell lymphoma 2 (BCL-2) expression and cell cycling of CD56bright NK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56bright NK cell degranulation appeared intact in all cohorts, we observed impaired IL-7-activated NK cell cytolytic function in HCV- and HIV-infected subjects. Finally, IL-7-induced phosphorylation of STAT-5 (pSTAT-5) signaling was impaired in NK cells of subjects with chronic viral infection, and this was reversible upon 6 mo of viral suppression with IFN-free HCV therapy. These results implicate that IL-7-dependent NK cell activation and effector function may be other host immune surveillance mechanisms that are impaired in viral infections.

Background Leprosy in children under 15 years of age, and in particular, the presence of leprosy grade 2 disability (G2D) in children, signifies ongoing transmission and the need for improved surveillance. Our objective was to describe the epidemiology of pediatric leprosy in Minas Gerais, Brazil and to explore associations with access to medical facilities. Methods A cross-sectional study was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN) from 2002–2017. Incident cases were included if they resided in a municipality with both adult and pediatric cases. Municipalities were divided by the number of medical facilities per municipality: < 5, 5–17, and 18 or higher. Analyses compared pediatric cases across two time periods (2002–2009 and 2010–2017) and number of medical facilities / municipality using chi-square, t-tests, and logistic regression. Results A total of 27,725 cases were reported with 1,611 under 15 years of age. Overall incidence declined from 34.8 per 100,000 to 13.6 per 100,000 during the study period with pediatric incidence declining from 2.6 per 100,000 to 0.8 per 100,000. Time period 2 (TP2) showed an increase in the proportion of pediatric G2D (2.58% vs 1.91%, p < 0.0001) when compared to time period 1 (TP1). Mean age of diagnosis in children was younger in TP2 then in TP1 (10.06 vs 10.43, p=0.02). In 2017, the pediatric incidence in municipalities with the fewest medical facilities was 0.95 per 100,000 compared to 0.23 per 100,000 in municipalities with > 5 facilities (p=0.009). There was significantly higher odds of disability at diagnosis (grades 1 and 2) in pediatric cases residing in municipalities with < 5 medical facilities (aOR 1.88; 95% CI 1.37–2.59), adjusted for age and sex. See map (Fig 1). Figure 1. Cases of Pediatric Disability By Number of Municipality Medical Facilities from 2002–2017 (White areas without reported pediatric leprosy) Conclusion The increasing proportion of G2D in children in the second half of the study period despite declining incidence suggest occult infections among children and adults alike in Minas Gerais. Furthermore, the average age of diagnosis in children should increase, not decrease, if M. leprae transmission was truly declining. Lastly, the association between fewer municipality health facilities and increased disability suggest barriers to timely diagnosis and a critical area of focus for research into access to healthcare and leprosy risk. Disclosures All Authors: No reported disclosures

Lactobacillus colonization of the lower female genital tract provides protection from the acquisition of sexually transmitted diseases, including human immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in vaginal epithelium is thought to support Lactobacillus colonization in vivo, many Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated how glycogen could be utilized by vaginal lactobacilli in the genital tract. Several Lactobacillus isolates were confirmed to not grow in glycogen, but did grow in glycogen-breakdown products, including maltose, maltotriose, maltopentaose, maltodextrins, and glycogen treated with salivary α-amylase. A temperature-dependent glycogen-degrading activity was detected in genital fluids that correlated with levels of α-amylase. Treatment of glycogen with genital fluids resulted in production of maltose, maltotriose, and maltotetraose, the major products of α-amylase digestion. These studies show that human α-amylase is present in the female lower genital tract and elucidates how epithelial glycogen can support Lactobacillus colonization in the genital tract.