HIV-negative Population Research Articles

Clinical outcomes post transition to adult services in young adults with perinatally acquired HIV infection: mortality, retention in care and viral suppression.

Adolescence is the only age group globally where HIV-associated mortality is rising, with poorer outcomes at all stages of the care cascade compared with adults. We examined post transition outcomes for young adults living with perinatal HIV. Retrospective cohort analysis. A tertiary Youth Friendly Service London, UK. A total of 180 young adults living with perinatal HIV registered between 1 January 2006 and 31 December 2017 contributed 921 person-years of follow-up post transition to adult services. Youth Friendly Service with multidisciplinary care and walk-in access. Mortality, morbidity, retention in care, antiretroviral therapy (ART) uptake and HIV-viral load suppression. Crude incidence rates are reported per 1000 person-years. Of 180 youth registered, four (2.2%) died, 14 (7.8%) transferred care and four (2.2%) were lost to follow-up. For the 158 retained in care, the median age was 22.9 years [interquartile ranges (IQR) 20.3-25.4], 56% were female, 85% Black African, with a median length of follow-up in adult care of 5.5 years (IQR 2.9-7.3). 157 (99.4%) ever received an ART prescription, 127/157 (81%) with a latest HIV-viral load less than 200 copies RNA/ml, median CD4 cell count of 626 cells/μl (IQR 441-820). The all-cause mortality was 4.3/1000 person-years [95% confidence interval (CI) 1.2-11.1], 10 fold the aged-matched UK HIV-negative population [0.43/1000 person-years (95% CI 0.41-0.44)]. Post transition, 17/180 (9.4%) developed a new AIDS diagnosis; crude incidence rates 18.5/1000 person-years (95% CI 10.8-29.6). While this youth-friendly multidisciplinary service achieved high engagement and coverage of suppressive ART, mortality remains markedly increased compared with the general UK population.

Systemic lupus erythematosus in the setting of HIV-1 infection: a longitudinal analysis.

Patients with concomitant HIV-1 infection and systemic lupus erythematosus (SLE) followed longitudinally at an HIV outpatient clinic from 1994 to 2019 were examined. Patients met 1982 and 1997 ACR classification criteria for SLE at the Thomas Street clinic from 1994 to 2019. Clinical and demographic comparisons were made with a non HIV-SLE patient cohort, the Lupus in Minorities Studies, Nature versus Nurture (LUMINA) study. Twenty-two patients with concomitant HIV-1 infection and SLE were identified, including 18 females, 3 males, and 1 male to female transgender. Overall, 81.8% of SLE-HIV patients were African-American compared to 55.3% of the 5856 patients seen at the HIV clinic from 2016 to 2017 (p= 0.02, OR = 3.6). There were 12 patients that developed HIV-1 in the setting of SLE and 10 patients that developed SLE in the setting HIV-1. This demographic distribution was significant when compared with the 1604 unique patients in the HIV rheumatology clinic from 1994 to 2019 (p= 0.03, OR = 5.9) and also significant when compared with the 5856 patients attending the county HIV clinic overall in 2016-2017 (p= 0.008, OR = 7.2). When comparing with the non-HIV SLE cohort, anti-dsDNA antibodies were noted less frequently in all HIV-SLE patients (p= 0.0002) including all sub-cohorts of our patients. Skin/mucosal involvement (p= 0.0003) and cytopenias (p= 0.0001) occurred less frequently in the patients that were diagnosed with HIV after their SLE diagnosis compared to non-HIV SLE patients. In a large county HIV clinic setting, the prevalence of SLE was significantly higher in African American women. Anti-dsDNA antibodies were less frequent in HIV-1 positive SLE patients.Key Points• This paper presents clinical and laboratory data on the largest cohort of SLE patients with HIV-1 infection reported to date.• The prevalence of SLE in a large outpatient HIV-1 clinic was larger than reported in HIV negative population studies.• The prevalence of SLE was particularly high in black HIV-1 infected women.• Skin/mucosal involvement and anti-ds DNA antibodies were less common in patients with HIV-1 and SLE compared to patients with SLE without SLE>.

Correction to: Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

Treating cancer with immunotherapy in HIV-positive patients: A challenging reality

Immunotherapy has widely changed the management of different malignancies. However, efficacy and safety of immune checkpoint inhibitors (ICIs) are not well established in people living with HIV (PLWH). Population of HIV-positive patients has deeply changed after the introduction of modern antiretroviral therapy (ART) and available data of immunotherapy in this subgroup are inadequate considering that cancer has become a leading cause of death and morbidity in this population. Moreover, there are many similarities between cancer and infectious antigen stimulation so that ICIs are even under evaluation as specific HIV treatment. Most of literature on this topic is based on small case series that suggest that immunotherapy for PLWH seems to be as effective as in HIV-negative population with a good safety profile. In this article we review literature on HIV and immunotherapy and we collect many case series available in different malignancies, with a brief focus on lung cancer.

Incidence and Outcomes of Pneumocystis pneumonia When Utilizing PCR-Based Diagnosis in Patients with Hodgkin Lymphoma Receiving Intensive Chemotherapy

Background: The overall incidence of Pneumocystis Pneumonia (PJP) in lymphoma varies according to diagnosis, host factors and treatment rendered.(Carmona, et al. 2011) A meta-analysis suggested that prophylaxis is appropriate when the chance of incurring PJP is 3.5% or greater.(Green, et al. 2007) Accurately characterizing the incidence of PJP is further complicated by a transition in diagnostic methods from direct immunofluorescence assay (DFA) to a DNA-based polymerase chain reaction (PCR) technique.(Caliendo et al., 1998, Wilson JW, et al., 2011) The incidence of PCR-based diagnosis of PJP and the need for anti-Pneumocystis prophylaxis in patients diagnosed with Hodgkin lymphoma receiving chemotherapy requires further investigation. Methods: This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Consecutive adult patients with a diagnosis of Hodgkin lymphoma receiving chemotherapy between January 2006 and August 2018 were evaluated. Patients with history of bone marrow transplant were excluded. Kaplan-Meier estimation was used to calculate the cumulative incidence of PJP with a 95% confidence interval. Cox proportional hazard models were used to demonstrate the strength of association between the independent variables and PJP rate. Results: The 506 included patients had a median (IQR) age of 40.3 (28.6, 59.7) years, 287 (56.7%) were male, and 470 (92.9%) were Caucasian. Further baseline demographics and clinical characteristics are described in table 1 with no significant differences between those diagnosed and those free from PJP. Chemotherapy combined with radiation therapy was prescribed for 163 (32.3%) patients while 342 (67.7%) patients received chemotherapy alone. Chemotherapy regimen distribution included 356 patients (70.4%) receiving bleomycin-containing chemotherapy. Median (IQR) total Bleomycin dose was 122 (IQR: 78, 178) Units. Bleomycin-containing combination chemotherapy regimen was not significantly associated with a higher risk for PJP when compared to other combination regimens (HR=1.59, 95% CI 0.55-4.62 p=0.40). Bleomycin-related lung compromise was suspected in 130 (25.7%) patients. Anti-pneumocystis prophylaxis was provided for 97 patients (n=39 a priori, 58 after chemotherapy initiation) and this was not significantly associated with a decreased incidence of PJP (HR=0.51, 95% CI 0.15-1.71, p=0.28). The cumulative incidence of PJP 1 year after start of chemotherapy was 6.2% (95% CI 3.8%-8.5%) and is shown in figure 1. Diagnosis of PJP occurred most commonly during the 2nd (n=8, 30.7%), 3rd (n=8, 30.7%), and 4th (n=7, 26.9%) cycles of chemotherapy. Trimethoprim-sulfamethoxazole was the only agent prescribed as PJP management. There were 10 (38%) patients with PCP that required ICU admission with 9 needing mechanical ventilation, 4 necessitating vasopressor support, and none requiring dialysis. Mortality 30-days from PJP diagnosis was 8% (n=2) with one death attributable to PJP infection. Conclusion: Cumulative incidence of PJP was 6.2% in patients receiving intensive chemotherapy for Hodgkin lymphoma. As the incidence is above the 3.5% threshold previously described, the clinician should consider the potential value of prophylaxis. Defining the overall utility of universal vs. targeted anti-pneumocystis prophylaxis requires further prospective, randomized investigation. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Trimethoprim/Sulfamethoxazole, Pentamidine isethionate, and dapsone will be discussed as prevention of Pneumocystis Pneumonia in the HIV-negative population

A Randomized Trial of EPOCH-Based Chemotherapy with Vorinostat for Highly Aggressive HIV-Associated Lymphomas: Updated Results Evaluating Impact of Diagnosis-to-Treatment Interval (DTI) and Pre-Protocol Systemic Therapy on Outcomes

Introduction: EPOCH-based chemotherapy is considered a preferred first-line treatment for HIV-associated diffuse large B-cell lymphoma (DLBCL) and primary effusion lymphoma in the 2019 NCCN guidelines. We previously reported that adding the HDAC inhibitor vorinostat (VOR) to EPOCH had no impact on complete response (CR) rate, the primary trial endpoint, and similar 1-year survival rates (ASCO 2018, abstract 7573). Here, we report updated results from AMC075 and evaluate the impact of a DTI ≥15 days on clinical outcomes. A DTI ≥15 days has been shown to be associated with a better prognosis in an HIV-negative population treated with R-CHOP (Maurer et al. J Clin Oncol 2018; 36:1603-1610). We also look at the impact of allowing 1 cycle of systemic therapy given prior to study enrollment in order to circumvent logistical challenges in recruiting otherwise eligible trial subjects. Methods: Between 2012 and 2017 we conducted a randomized phase II study of EPOCH (with rituximab in CD20+ tumors) ± VOR 300 mg administered on days 1-5 of each cycle with HIV antiretroviral therapy in 90 participants with aggressive HIV-NHLs. Eligible patients had at least one of the following high-risk features or tumor characteristics: Age-adjusted International Prognostic Index (aa-IPI) of 2-3, Ki-67 ≥ 80%; activated B-cell (ABC) diffuse large B-cell lymphoma(DLBCL); or any other aggressive non-germinal center (non-GCB), non-Burkitt B-cell NHL. Patients who received 1 prior cycle of chemotherapy (CHOP-like or EPOCH) +/- rituximab were allowed to register. The primary endpoint was CR rate. Secondary objectives included determining adverse events, survival rates, and the effect of EPOCH +/- VOR on HIV viral reservoirs. We performed a post-hoc analysis evaluating the impact of time from DTI ≥15 days vs. <15 days on clinical outcomes and that of pre-protocol systemic therapy. Results: Of 86 evaluable patients, 64 had DLBCL (34 GCB-type and 27 ABC-type), 15 plasmablastic lymphoma (PBL), and 7 primary effusion lymphoma (PEL) [Table 1]. Fifty-one (59%) patients were treatment naïve, whereas 35 (41%) had been pre-treated with one cycle of CHOP-like or EPOCH prior to enrollment. Grade 4 neutropenia was more frequent for VOR-EPOCH than for EPOCH (47% vs. 20%), and also grade 4 thrombocytopenia more frequent for VOR-EPOCH (29% vs 2%). The two regimens had similar rates of febrile neutropenia (18% vs. 16%). CR rates were also comparable for the two regimens (68% vs. 74%) [1-sided P=0.72] (Table 1). Median HIV plasma RNA generally decreased in both arms. No significant differences were observed in T-cell subsets or size of the latent HIV reservoir between arms. Treatment outcomes did not differ significantly across NHL subtypes or EBV status (Table 1), nor with pre-protocol systemic therapy (Table 2). Overall CR rates were 45% in patients with CD4+ counts of 50-100 cells/mm3, 63% with 100-199 cells/mm3, and 85% in patients with >200 cells/mm3(Table 1). The 3-year overall survival rates for VOR-EPOCH was 70% and for EPOCH 77% (log-rank P=0.39), and 3-year event-free survival rates were 63% vs. 69%, respectively (log-rank P=0.32) [Figure 1]. Thirty-six patients (86% of n=42) with long DTI (≥15 days) had CR, compared to only 25 (57% of n=44) with short (<15 days) DTI (P=0.0032). The proportion of patients with short DTI was somewhat higher (63%) in the pre-treated group than in the treatment-naïve group (43%; P=0.072) without significant difference in CR or survival rates (Table 2). Conclusion: This prospective trial demonstrated that EPOCH-based chemotherapy was broadly efficacious against aggressive HIV-NHLs, including high risk subtypes (ABC DLBCL, PBL, and PEL). However, a 5-day course of VOR given with each chemotherapy cycle failed to improve outcomes. Consistent with prior reports in HIV-uninfected patients with DLBCL, a DTI of ≥15 days was associated with better clinical outcomes than a shorter DTI. A strategy of permitting pre-protocol therapy was useful in facilitating accrual and was used in about 40% of study participants without compromising clinical outcomes. Disclosures Baiocchi: Prelude: Consultancy. Noy:Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. OffLabel Disclosure: Vorinostat is being tested in combination with chemotherapy for HIV-associated B-cell lymphoma

1405. Infectious Causes of Chronic Meningitis in HIV-Negative Patients: A Case Series

BackgroundChronic meningitis can be defined as inflammation of the cerebrospinal fluid (CSF) with the presence of >5 white blood cells/mm3 of CSF for 4 weeks. There is little literature available on defining the infectious causes or risk factors of chronic meningitis, and there are no studies that have looked at mortality in this group of patients. Our aim for this study was to evaluate the epidemiology, risk factors, and mortality of infectious causes of chronic meningitis within our healthcare system.MethodsA total of 59 cases were identified through a systematic retrospective review from our electronic medical record database from 2004 to 2018 and were identified by having the presence of two consecutive lumbar punctures with a white blood cell count in CSF >5 WBC/mL3 in a 4-week period, or by having 4 weeks of meningeal symptoms with one lumbar puncture with >5 WBC/mL3. All cases were manually reviewed. We excluded patients with diagnosis of human immunodeficiency virus (HIV) infection. We included a review of comorbidities that could impair the immune system such as diabetes mellitus, alcohol use, chronic kidney disease (CKD) stage III or greater use of chemotherapy, immunotherapy, or chronic use of steroids and previous transplant recipients. The study was approved by the institutional review boardResults59 cases of chronic meningitis attributable to an infectious etiology were identified. The most common pathogens were Borrelia burgdorferi (37%), Cryptococcus sp. (27%), and Candida sp. (10%). Other etiologies which were less common included viral etiologies (13%). Finally, there were two cases secondary to Streptococcus pneumonia. Regarding the total number of patients with the comorbidities studied, 13 (22%) had diabetes, 12 (20%) had CKD, 12 (20%) were under some form of chemo/immunotherapy including chronic steroid use and 3 (5%) of patients were transplant recipients.ConclusionOur study identified common infectious pathogens causing chronic meningitis in a rural, HIV-negative population. Our findings indicate that cryptococcus should be considered even within HIV-negative individuals, and Lyme disease should be considered in all endemic areas. Mortality was significant among patient with cryptococcal meningitis, where patients with Lyme meningitis did very well. Disclosures All authors: No reported disclosures.

Seroprevalence and associated factors of Toxoplasma gondii among HIV-infected patients in Tokyo: A cross sectional study

HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p < 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p < 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis.

PF529 PROGNOSTIC CORRELATION OF CELL‐OF‐ORIGIN AND MYC, BCL‐2 AND BCL‐6 STATUS IN HIV‐ASSOCIATED DIFFUSE LARGE B‐CELL LYMPHOMAS

Background:Diffuse Large B‐cell lymphoma (DLBCL) can be classified by gene expression profiling (GEP) into 3 subtypes according to the putative Cell‐Of‐Origin (COO): the germinal center B‐cell type (GCB), the activated B‐cell type (ABC) and the unclassifiable type (UC). Immuno‐histochemistry (IHC) algorithms, being Hans's the mostly used, and NanoString (NS) 20‐genes assay can surrogate adequately GEP in COO assignment. In DLBCL HIV negative population treated with rituximab‐CHOP, GCB type is associated with a better outcome, while gene rearrangements of MYC plus BCL‐2 and/or BCL‐6 detected by fluorescence in situ hybridization (FISH) confer a worse prognosis. In HIV positive DLBCL, limited data are available on COO subtypes and genes rearrangements incidences and on their prognostic significance.Aims:To evaluate in HIV‐associated DLBCL: the proportion of COO subtypes defined by IHC and NS assay and the concordance of these methods; the prognostic impact of COO and of MYC, BCL‐2 and BCL‐6 status.Methods:We retrospectively analyzed 66 HIV positive patients (pts) with newly diagnosed DLBCL from 2000 to 2016. Histological samples were centrally reviewed for diagnosis confirmation, COO assignment according to Hans and MYC, BCL‐2 and BCL‐6 protein expression. NS Lymph2Cx assay was applied for COO identification and FISH using break‐a‐part probes for MYC, BCL‐2 and BCL‐6 gene analysis.Results:Pts characteristics at DLBCL diagnosis were: 73% male, median age 45 yrs (range: 28–83), 80% advanced stage, 34% high‐intermediate or high IPI score and median CD4+ cell count 188/microL (range: 8–1172). An anthracycline‐containing first‐line chemotherapy was delivered to 97% of pts with the addition of rituximab in 86%. By IHC COO assigned was GCB in 31 (47%) and non‐GCB in 35 (53%) cases. COO by NS was determined in 60 pts: 34 pts were GCB (57%), 11 ABC (18%) and 15 UC (25%). Hans algorithm and NS assay concordantly assigned COO subtypes in 80% of cases (Cohen's kappa = 0.604; p &lt; 0.0005). After a median follow‐up of 50 months, 2‐yrs progression‐free survival (PFS) and overall survival (OS) of the entire series were 56% and 61%, respectively. No statistically significant survival difference was found according to IHC and NS COO assignment, although a trend for a superior OS in GCB subtype defined by NS was observed (2‐yrs OS: 71% vs 53%, p = 0.078). MYC, BCL‐2, BCL‐6 proteins expression and gene rearrangements are summarized in Table 1. BCL‐2 overexpression was detected in 22 pts (34%), was not sustained by BCL‐2 rearrangement and was associated with an inferior OS (2‐yrs OS 48% vs 67%, p = 0.047, HR: 2.04). MYC protein overexpression and MYC, BCL‐2, BCL‐6 gene rearrangements, both single or combined, did not impact survival. Stage IV and elevated LDH were associated with inferior PFS (p = 0.024 and p = 0.017) and OS (p = 0.014 and p = 0.027). A baseline CD4+ count &gt;200/microL had a protective role for both progression and death (2‐yrs PFS: 63% vs 42%, p = 0.013, HR: 0.40; 2‐yrs OS: 72% vs 42%, p = 0.002, HR: 0.29). At multivariate analysis, only CD4+ count &gt;200/microL was associated with superior PFS and OS.Summary/Conclusion:In HIV‐associated DLBCL we found an high concordance between Hans algorithm and NS in the COO subtypes allocation, with subgroups distribution by NS similar to what described in the HIV negative population. The trend for superior outcome in GCB type by NS needs to be confirmed in a larger cohort, as well as the prognostic role of MYC, BCL‐2, BCL‐6 status. DLBCL's adverse clinical features and severe immundeficiency correlated with a dismal prognosis, as expected.image

P.103 When a neurosurgeon should care about pneumonia: the case for Pneumocystis jirovecii pneumonia prophylaxis in neurosurgical patients

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic interstitial fungal pneumonia. The incidence of PJP in HIV-positive populations is decreasing, while it is increasing in HIV-negative immunocompromised populations, such as neurosurgical patients treated with high-dose corticosteroids. Morbidity and mortality can be severe owing to acute respiratory failure. Methods: Two cases are described and a literature review performed to determine the incidence of PJP in the neurosurgery population. A standardized care pathway is proposed to reduce preventable harm. Results: Long-term, high-dose corticosteroid regimens (≥4 mg dexamethasone daily for ≥4 weeks) with taper are associated with increased risk of PJP infection. Additional risk factors for infection in HIV-negative patients include CNS malignancy and concurrent radiation therapy. TMP-SMX is the first-line agent for PJP prophylaxis. Conclusions: Clinicians should maintain a high index of suspicion of PJP and adopt a standardized protocol for prophylaxis in neurosurgical patients treated with high-dose corticosteroids.

Developing a dynamic HIV transmission model for 6 U.S. cities: An evidence synthesis.

BackgroundDynamic HIV transmission models can provide evidence-based guidance on optimal combination implementation strategies to treat and prevent HIV/AIDS. However, these models can be extremely data intensive, and the availability of good-quality data characterizing regional microepidemics varies substantially within and across countries. We aim to provide a comprehensive and transparent description of an evidence synthesis process and reporting framework employed to populate and calibrate a dynamic, compartmental HIV transmission model for six US cities.MethodsWe executed a mixed-method evidence synthesis strategy to populate model parameters in six categories: (i) initial HIV-negative and HIV-infected populations; (ii) parameters used to calculate the probability of HIV transmission; (iii) screening, diagnosis, treatment and HIV disease progression; (iv) HIV prevention programs; (v) the costs of medical care; and (vi) health utility weights for each stage of HIV disease progression. We identified parameters that required city-specific data and stratification by gender, risk group and race/ethnicity a priori and sought out databases for primary analysis to augment our evidence synthesis. We ranked the quality of each parameter using context- and domain-specific criteria and verified sources and assumptions with our scientific advisory committee.FindingsTo inform the 1,667 parameters needed to populate our model, we synthesized evidence from 59 peer-reviewed publications and 24 public health and surveillance reports and executed primary analyses using 11 data sets. Of these 1,667 parameters, 1,517 (91%) were city-specific and 150 (9%) were common for all cities. Notably, 1,074 (64%), 201 (12%) and 312 (19%) parameters corresponded to categories (i), (ii) and (iii), respectively. Parameters ranked as best- to moderate-quality evidence comprised 39% of the common parameters and ranged from 56%-60% across cities for the city-specific parameters. We identified variation in parameter values across cities as well as within cities across risk and race/ethnic groups.ConclusionsBetter integration of modelling in decision making can be achieved by systematically reporting on the evidence synthesis process that is used to populate models, and by explicitly assessing the quality of data entered into the model. The effective communication of this process can help prioritize data collection of the most informative components of local HIV prevention and care services in order to reduce decision uncertainty and strengthen model conclusions.

Brain structure of perinatally HIV-infected patients on long-term treatment: A systematic review.

We aim to give an overview of the available evidence on brain structure and function in PHIV-infected patients (PHIV+) using long-term combination antiretroviral therapy (cART) and how differences change over time. We conducted an electronic search using MEDLINE, Embase, and PsycINFO. We used the following selection criteria: cohort and cross-sectional studies that reported on brain imaging differences between PHIV+ of all ages who used cART for at least six months before neuroimaging and HIV-negative controls. Two reviewers independently selected studies, performed data extraction, and assessed quality of studies. After screening 1500 abstracts and 343 full-text articles, we identified 19 eligible articles. All included studies had a cross-sectional design and used MRI with different modalities: structural MRI (n = 7), diffusion tensor imaging (DTI) (n = 6), magnetic resonance spectroscopy (n = 5), arterial spin labeling (n = 1), and resting-state functional neuroimaging (n = 1). Studies showed considerable methodological limitations and heterogeneity, preventing us to perform meta-analyses. DTI data on white matter microstructure suggested poorer directional diffusion in cART-treated PHIV+ compared with controls. Other modalities were inconclusive. Evidence may suggest brain structure and function differences in the population of PHIV+ on long-term cART compared with the HIV-negative population. Because of a small study population, and considerable heterogeneity and methodological limitations, the extent of brain structure and function differences on neuroimaging between groups remains unknown.

Abstract 239: Prevalence and Predictors of Diastolic Dysfunction in HIV-Infected and HIV-Negative Tanzanian Adults: A Cross-sectional Study

Objective: To compare the prevalence and predictors of myocardial dysfunction in HIV-infected and HIV-negative Tanzanian adults. Methods: A cross-sectional study including 256 HIV-infected, ART-naïve and 263 HIV-negative Tanzanian adults. Traditional cardiovascular risk factors for myocardial dysfunction (age, sex, hypertension, body mass index, abdominal obesity and tobacco use) were determined by standard investigations. Bedside echocardiography was performed at time of enrollment. The primary outcome was echocardiographic prevalence of myocardial systolic and/or diastolic dysfunction as classified by the American Society of Echocardiography/European Association of Echocardiography guidelines. Results: The average age of HIV-negative and HIV-infected participants was similar (36.8 vs 36.6 years). No study participants met criteria for systolic dysfunction. Compared with HIV-negative controls, more HIV-infected adults were classified as diastolic dysfunction (OR[CI]: 2.47[1.61-3.80], [78/256 (30.7%) vs 40/263 (15.2%)], p&lt;0.0001, respectively), with HIV-infected adults also classified as Grade II/III more commonly than those HIV-negative (p=0.04). Diastolic dysfunction was significantly associated with hypertension, age and diastolic and systolic blood pressure in both HIV-infected and HIV-negative participants (3.26[1.56-6.81] and 5.67[2.68-11.99], 1.13[1.08-1.17] and 1.11[1.07-1.15], 1.03[1.01-1.06] and 1.09[1.06-1.13], 1.02[1.01-1.04] and 1.05[1.02-1.07], respectively). CD4 count was also associated with diastolic dysfunction in HIV-infected participants (0.998[0.997-0.999]). Additionally, HIV-infected participants required fewer traditional risk factors for dysfunction prevalence Probability of disease with one or fewer risk factors present was greater in HIV-infected as compared to HIV-negative adults (p=0.02). Conclusions: HIV-infected Tanzanian adults have a higher prevalence of myocardial diastolic dysfunction and have more advanced disease as compared to HIV-negative controls. This dysfunction is present at a much younger age and with fewer traditional risk factors than previously reported HIV-negative populations. The most significant predictor for diastolic dysfunction is hypertension; therefore, echocardiography may be indicated for hypertensive, HIV-infected adults, independent of age.

Missed opportunities for earlier diagnosis of HIV in British Columbia, Canada: A retrospective cohort study.

BackgroundLate HIV diagnosis is associated with increased AIDS-related morbidity and mortality as well as an increased risk of HIV transmission. In this study, we quantified and characterized missed opportunities for earlier HIV diagnosis in British Columbia (BC), Canada.DesignRetrospective cohort.MethodsA missed opportunity was defined as a healthcare encounter due to a clinical manifestation which may be caused by HIV infection, or is frequently present among those with HIV infection, but no HIV diagnosis followed within 30 days. We developed an algorithm to identify missed opportunities within one, three, and five years prior to diagnosis. The algorithm was applied to the BC STOP HIV/AIDS population-based cohort. Eligible individuals were ≥18 years old, and diagnosed from 2001–2014. Multivariable logistic regression identified factors associated with missed opportunities.ResultsOf 2119 individuals, 7%, 12% and 14% had ≥1 missed opportunity during one, three and five years prior to HIV diagnosis, respectively. In all analyses, individuals aged ≥40 years, heterosexuals or people who ever injected drugs, and those residing in Northern health authority had increased odds of experiencing ≥1 missed opportunity. In the three and five-year analysis, individuals with a CD4 count <350 cells/mm3 were at higher odds of experiencing ≥1 missed opportunity. Prominent missed opportunities were related to recurrent pneumonia, herpes zoster/shingles among younger individuals, and anemia related to nutritional deficiencies or unspecified cause.ConclusionsBased on our newly-developed algorithm, this study demonstrated that HIV-diagnosed individuals in BC have experienced several missed opportunities for earlier diagnosis. Specific clinical indicator conditions and population sub-groups at increased risk of experiencing these missed opportunities were identified. Further work is required in order to validate the utility of this proposed algorithm by establishing the sensitivity, specificity, positive and negative predictive values corresponding to the incidence of the clinical indicator conditions among both HIV-diagnosed and HIV-negative populations.

Alterations in bacterial communities, SCFA and biomarkers in an elderly HIV-positive and HIV-negative population in western Mexico

BackgroundThe study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects.MethodsA cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA.ResultsAn increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group.ConclusionsAlterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.

3166 Association between HIV and early weight loss and the impact on subsequent treatment outcomes among patients with tuberculosis

OBJECTIVES/SPECIFIC AIMS: Previous research suggests that weight loss during early TB treatment (first two months of anti-TB therapy) is a predictor of poor tuberculosis (TB) treatment outcomes among HIV-negative populations, but the relationship has not been well studied in the context of HIV. We examined the association between HIV and weight change during the first two months of anti-tuberculosis treatment, and also assessed the effects of HIV and early weight change on tuberculosis (TB) treatment outcomes. METHODS/STUDY POPULATION: Adults with culture-confirmed, drug-susceptible, pulmonary TB, regardless of HIV status, were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil cohort and followed on standard anti-TB therapy. For the primary analysis, we compared weight change in persons living with HIV (PLWH) and HIV-negative patients between baseline and two months using multivariable bootstrapped quantile regression and modified Poisson regression. For secondary analysis, we examined the separate effects of HIV and weight change on poor TB treatment outcome (treatment failure, TB recurrence, or death) using Cox proportional hazards regression. RESULTS/ANTICIPATED RESULTS: Among 323 participants, 45 (14%) were HIV-positive. On average, PLWH lost 0.7% (interquartile range (IQR): −5.1%, 4.4%) of their baseline body weight between baseline and two months; those without HIV gained 3.5% (IQR: 0.8%, 6.7%). After adjusting for age, sex, and baseline BMI, PLWH lost 4.1% (95% confidence interval (CI): −6.5%, −1.6%) more weight during the first two months of anti-TB treatment than HIV-negative individuals. HIV infection was associated with weight loss ≥5% (adjusted odds ratio = 9.3; 95% CI: 4.2-20.6). Regarding the secondary analysis, 14 patients had a poor TB treatment outcome: 2 treatment failures, 4 cases of recurrent TB, and 8 deaths. PLWH and patients who lost ≥5% weight had significantly increased risk of poor TB treatment outcome with hazard ratios of 8.77 (95% CI: 2.96-25.94) and 4.09 (95% CI: 1.11-15.14), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that HIV is associated with weight loss during early TB treatment, and both HIV and early weight loss were associated with poor treatment outcome. Future research should examine the potential etiologies of these findings and identify the types of interventions that would best promote weight gain during TB treatment, especially among PLWH, in order to prevent poor TB treatment outcomes.

Low rate of gut colonization by extended-spectrum β-lactamase producing Enterobacteriaceae in HIV infected persons as compared to healthy individuals in Nepal.

A worldwide increase in the gastrointestinal colonization by extended-spectrum β-lactamase (ESBL)-producing bacteria has been observed. Their prevalence amongst Healthy People Living with HIV (HPLWH) has not been investigated adequately. The aim of this study was to determine and compare the rates of and risk factors for intestinal carriage and acquisition of extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) among healthy people living with HIV (HPLWH) and healthy HIV negative population in the community. A cross-sectional study was conducted. Rectal swabs from HPLWH (n = 119) and HIV negative individuals (n = 357) from the community were screened for ESBL and CPE. Phenotypically confirmed ESBL-E strains were genotyped by multiplex PCR. The risk factors associated with ESBL-E colonization were analyzed by a multivariable conditional logistic regression analysis. Specimen from 357 healthy volunteers (213 female and 144 male) and 119 HPLWH (82 female and 37 male) with a median age of 30 [IQR 11–50] years were included in the study. ESBL colonization were found in 45 (37.82% [CI 29.09, 47.16]) and 246 (68.91% [CI 63.93, 73.49]), HPLWH and healthy HIV negative participants respectively. HPLWH had lower ESBL carriage rate (odds ratio 0.274 [CI 0.178, 0.423]) compared to healthy HIV negative subject’s (p<0.01). In this study, no carbapenemase-producing bacteria were isolated.CTX-M-15 type was the most predominant genotype in both groups. Livestock contact and over-the-counter medications were significantly associated with a higher ESBL-E carriage rate among healthy subjects. This is the first study in Nepal that has demonstrated a high rate of gut colonization by ESBL-E in the community, predominantly of blaCTX-M-15 genotype. This study divulges the low fecal carriage rate of ESBL producing bacteria in HPLWH group compared to healthy individuals in western Nepal. The factors responsible for this inverse relationship of HIV status and gut colonization by ESBL-E are unidentified and require further large-scale study.

Breast cancer, human immunodeficiency virus and highly active antiretroviral treatment; implications for a high-rate seropositive region.

Sub-Saharan Africa is the region in the world with the most people infected with the human immunodeficiency virus (HIV). The incidence of breast cancer is also rising in the region. This transcript focusses on the burden of these two diseases when they converge in the same populace. This comprehensive literature review of the topic suggests a trend towards an increasing incidence of breast cancer in the HIV-infected population, and the rationale for such a tendency is hypothesized, especially in the context of the availability of highly active antiretroviral therapy. Besides the age at diagnosis, all other clinical characteristics appear to be similar in HIV-positive and HIV-negative breast cancer populations. Outcomes of the different treatment modalities for breast cancer in HIV-positive patients are also appraised and finally innovative areas of future research are suggested along with plausible recommendations.

Prevalence of metabolic syndrome among HIV-positive and HIV-negative populations in sub-Saharan Africa\u2014a systematic review and meta-analysis

BackgroundMetabolic syndrome (MetS) is a constellation of conditions that increase the risk of cardiovascular diseases. It is an emerging concern in sub-Saharan African (SSA) countries, particularly because of an increasingly aging population and lifestyle changes. There is an increased risk of MetS and its components among people living with Human immune deficiency syndrome (HIV) individuals; however, the prevalence of metabolic syndrome in the SSA population and its differential contribution by HIV status is not yet established. This systematic review and meta-analysis were conducted to estimate the pooled prevalence of metabolic syndrome in people living with HIV and uninfected populations, its variation by sub-components.MethodsWe performed a comprehensive search on major databases—MEDLINE (PubMed), EBSCOhost, and Cochrane Database of Systematic Reviews and Web of sciences for original epidemiological research articles that compared proportions of the MetS and its subcomponents between people living with HIV and uninfected patients and published between January 1990–December 2017. The inclusion criteria were adults aged ≥ 18 years, with confirmed HIV status. We assessed the risk of bias using a prevalence studies tool, and random effect meta-analyses were used to compute the pooled overall prevalence.ResultsA total of four cross-sectional studies comprising 496 HIV uninfected and 731 infected participants were included in the meta-analysis. The overall prevalence of MetS among people living with HIV was 21.5% (95% CI 15.09–26.86) versus uninfected 12.0% (95% CI 5.00–21.00%), with substantial heterogeneity. The reported relative risk estimate for MetS among the two groups was twofold (RR 1.83, 95% CI 0.98–3.41), with an estimated predictive interval of 0.15 to 22.43 and P = 0.055 higher for the infected population. Hypertension was the most prevalent MetS sub-components, with diverse proportions of people living with HIV (5.2–50.0%) and uninfected (10.0–59.0%) populations.ConclusionsThe high range of MetS prevalence in the HIV-infected population compared to the uninfected population highlights the possible presence of HIV related drivers of MetS. Also, the reported high rate of MetS, irrespective of HIV status, indicates a major metabolic disorder epidemic that requires urgent prevention and management programs in SSA. Similarly, in the era of universal test and treat strategy among people living with HIV cohorts, routine check-up of MetS sub-components is required in HIV management as biomarkers.Systematic review registrationPROSPERO CRD42016045727

Hiv and Lymphoma: from Epidemiology to Clinical Management.

Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop in the context of AIDS. HIV-associated lymphoma differs from lymphoma in the HIV negative population in that they more often present with advanced disease, systemic symptoms, and extranodal involvement and are frequently associated with oncogenic viruses (Epstein-Barr virus and/or human herpesvirus-8). Before the introduction of cART, most of these patients could not tolerate the treatment strategies routinely employed in the HIV-negative population. The widespread use of cART has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that nowadays can be compared to those seen in non-HIV infected patients. However, a great deal of attention should be paid to opportunistic infections and other infectious complications, cART-chemotherapy interactions, and potential cumulative toxicity. In the context of relatively sparse prospective and randomized trials, the optimal treatment of AIDS-related lymphomas remains a challenge, particularly in patients with severe immunosuppression. This paper will address epidemiology, pathogenesis, and therapeutic strategies in HIV-associated NHL and HL.