Viral Counts Research Articles

The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects

BackgroundCytokines play an important role in controlling the homeostasis of the immune system and infection with Human Immunodeficiency virus (HIV) leads to deregulated production of both pro- and anti-inflammatory cytokines. This study was designed to determine the effects of HIV and Highly Active Antiretroviral Therapy (HAART) on the levels of pro-and anti-inflammatory cytokines in HIV infected subjects.MethodA total of 50 HIV infected and 50 HIV seronegative control participants were recruited for the study. The HIV infected subjects were recruited before commencement of antiretroviral therapy and were followed up for 12 months. Blood samples were collected at 3 different points: before initiation of therapy, 6 months into therapy and 12 months into therapy. Serum cytokines were analyzed using ELISA method while CD4+ T cells and viral load counts were measured using standard laboratory methods.ResultThe results showed that pro-inflammatory cytokines: Tumour necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and anti-inflammatory cytokines Interleukin-4 (IL-4), Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) were significantly elevated in HIV infected subjects before commencement of therapy compared to 6 months and 12 months into therapy (P < 0.01) and compared to control participants (P < 0.01). TNF-α, TGF-beta remained significantly elevated even after 12 months of therapy compared to control participants (P < 0.01), while IL-4, IL-6, and IL-10 showed no significant difference compared to control participants after 12 months of therapy (P > 0.05). INF-γ was significantly reduced before commencement of therapy and after 12 months of therapy compared to control participants (P < 0.05) respectively.ConclusionTNF-α and TGF-β remained significantly elevated even after 12 months of therapy, while IFN-γ remained significantly reduced after 12 months of therapy. Regulating these cytokines which were unresponsive to therapy could serve as a potential measure of therapy for HIV infected subjects. The positive effect of 12 months therapy on IL-4, IL-6 and IL-10 levels can be used to monitor disease prognosis during therapy especially in resource poor setting where regular viral load monitoring is unavailable.

CCR5 delta32 Cord & Haploidentical Grafts: Allogeneic Stem Cell Transplant for HIV+ /AML Patient: A Case Report from the Impaact P1107 Observational Study

▪Background: Although current antiretroviral therapies have effectively changed the course of HIV-1 infection, it remains an incurable illness. The C-C chemokine receptor type 5 (CCR5) is the key co-receptor for HIV entry into CD4+ T cells. Homozygous 32 deletion (delta32) in CCR5 genes leads to resistance to HIV-1 infection 1. Allogeneic stem cell transplant from a donor with CCR5 delta32/32 mutation was curative for HIV in an HIV-1-infected man (Berlin Patient) with AML 2. It has been challenging to replicate this experience. We present our experience with a single case of successful engraftment of CD34-selected, related haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in an HIV-1-infected woman who, like the Berlin patient, developed AML and is now doing well at almost one-year post transplantation.Clinical case: A 60-year-old African-American woman was diagnosed with HIV-1- infection in June 2013 and was started on an antiretroviral treatment (ART) regimen consisting of tenofovir, emtricitabine and raltegravir. Her pre-ART viral load and CD4 counts were 1,000,000 copies/ml and 1003 cells/mm3, respectively. In Nov, 2013 she had viral load < 20 copies/ml with CD4 counts of 980 cells/mm3 and her HIV-1 infection was relatively asymptomatic. In March 2017, she was diagnosed with AML with monosomy 7. Her HIV therapy after the AML diagnosis was changed to abacavir- lamivudine -dolutegravir- combination. She achieved morphologic and cytogenetic remission after 1 cycle of standard idarubicin/cytarabine induction chemotherapy. In addition, she received 1 cycle of HiDAC consolidation and was referred for allogeneic stem cell transplant. We identified a CCR5 delta32/32 mutated cord blood unit (CBU) which was 5/8 HLA matched and contained 1.3 x 107 nucleated cells/kg and 3.2 x 104 CD34+ cells/kg.She underwent a combined CD34-selected, haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in August 2017. Her conditioning regimen was with fludarabine/melphalan/and TBI400 and she also received ATG/MMF/tacrolimus for GVHD prophylaxis. Her neutrophils and platelets engrafted on day 10 and 16, respectively and she was discharged on day +16 post-transplant. Her post-discharge hospital course was complicated by CMV reactivation (no organ involvement) 2 months post-transplant with peak viral level of 1374 copies/ml. She did not have evidence for EBV re-activation or graft-vs-host disease. Her plasma HIV viral load remained undetectable post- transplant while remaining on abacavir/lamivudine and dolutegravir-based ART.Her day+180 bone marrow showed continued AML remission and she remains in clinical remission near one year post-transplant. CD3 chimerism showed 82% haploidentical donor and 8% CBU and 10% recipient on day +15 post-transplant (Figure 1). The chimerism composition switched to 96% CBU by day+34, and became and remained 100% CBU since day+55. CD33 chimerism showed 98% haploidentical donor and 2% cord donor on day+15 post-transplant. It was 81% haploidentical donor and 19% cord on day+55 and became 100% cord by day+100. She has continued CD4, CD8, NK and CD19 cell recovery, with normal T cell subsets currently (Figure 2). Her CD4 count dropped to 27 cells/mm3 at one-month post-transplant and currently is at 673cells/mm3. She is currently 11 months post-transplant and is back to her normal daily activitiesConclusion: Haplo-cord transplantation with CCR5 delta 32/32 CBU resulted in rapid engraftment and immune replacement with dominance of the CCR5 delta 32/32 CBU graft in an HIV-1-infected woman. Successful suppression of HIV-1-replication to clinically undetectable levels was maintained throughout the transplant period for up to one year. . Correlative viral and immunological studies are ongoing, along with effects on the latent reservoir, which was detectable pre-transplant. It is possible to identify appropriate CCR5 delta 32/32 CBU units for haplo-cord transplantation in HIV-1- infected patients with implications for HIV-1 cure. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing

Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing

2571. Higher Rates of Hospitalization and Infection-Related Hospitalization Among HIV-Exposed Uninfected Infants Compared with HIV Unexposed Uninfected Infants in the United States

BackgroundStudies from multiple countries have suggested impaired immunity in perinatally HIV-exposed uninfected (HEU) children, with elevated rates of all-cause hospitalization and infections. We estimated the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU children and compared this with HIV-unexposed uninfected (HUU) children in the US Among HEU children, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of infant hospitalization.MethodsWe evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) Study dynamic cohort of the Pediatric HIV/AIDS Cohort Study (PHACS) network who were born 2006–2017 and followed from birth. Data on HUU children were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU children using Poisson regression. Among HEU children, multivariable Poisson regression models were fit to evaluate associations of maternal HIV factors with risk of hospitalization.ResultsOur analysis included 2,404 HEU and 3,605,864 HUU children. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUU children (figure). There was no significant difference in mortality. Among HEU children, maternal HIV disease factors, including viral load, CD4 count, antiretroviral regimen, and mode of HIV acquisition, were not associated with hospitalization rates.ConclusionCompared with HUU, HEU children in the United States have nearly twice the rate of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.Figure:Rates of Hospitalization and Mortality in First 2 Years of Life (95% CI) among SMARTT HEU versus Medicaid HUU in the United States, 2007–2016Disclosures E. G. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.

1903. Cost Minimization Analysis of a Preferred ARV Prescribing Pathway for Treatment-Naïve HIV-Positive Patients

BackgroundThere were 266 new attendees to the HIV clinic of St. James’ Hospital in 2016. HIV care is expensive. The modelled lifetime cost of treating one HIV-positive patient in the UK is estimated at £360,800, with ARVs accounting for 68% of the cost. This audit aims to assess potential savings in ARV spend if a cost-based prescribing approach was adopted for suitable treatment-naïve patients of the clinic.MethodsA retrospective analysis of newly attending HIV-positive patients attending the HIV Clinic in 2016 was undertaken. Treatment-naïve patients were identified. 2016 ARV drug acquisition costs were obtained from the St. James’ Hospital Finance department. The cost of first-line ARV regimens were calculated. Patients were evaluated for their suitability for the lowest-cost, first-line ARV regimen by analysing baseline viral loads, CD4 counts, resistance patterns, renal function, bone health and HLA B5701 status. The price difference between their prescribed regimens and the most cost-effective first-line regimen was calculated.ResultsFrom January to December 2016, there were 266 new attendances. One hundered fifty-four of these patients (58%) were treatment naïve. The treatment regimens were ascertained for 145/154 (94%). A cost difference of approx. €390 per month existed between the most expensive and least expensive first-line ARV regimens. The monthly cost of ARV regimens prescribed came to €152,949.09, equating to an annual spend of €1,835,389.08. The predicted monthly ARV cost of the cost-based prescribing approach has been calculated at €139,186.27 with an annual cost of €1,670,235.24. This would lead to an annual saving of €165.153.84, equating to 9% of the 2016 ARV spend for this population.ConclusionThis audit outlines the potential cost-effectiveness of a cost-based prescribing approach for suitable treatment-naïve patients that also adheres to best clinical practice guidelines. It demonstrates that significant cost savings (9%) can be made by simple analysis of ARV costs. These data can be used to support future options in ARV procurement and tender-processing for the department and nationally. It can also serve as a template in the construction of a pathway for the safe and cost-effective switching of ARV regimens of patients already on established regimens when generic ARV medications become available in Ireland.Disclosures All authors: No reported disclosures.

579. Acceptability of Home-Based Medical Assessment to Facilitate Re-engagement of HIV-Positive Out-of-Care Persons into Clinical Care, New York City

BackgroundFor people living with HIV (PLWH), retention in care and antiretroviral treatment improve individual health and curb further HIV transmission. Since 2007, New York City Health Department Disease Intervention Specialists (DIS) make contact attempts to re-engage PLWH presumed to be out-of-care (OOC) because they lack HIV registry report of viral load or CD4 cell count ≥9 months from selection date. Each year, 28–50% of OOC-PLWH refuse assistance from DIS to re-engage in HIV care. In 2017, we assessed the interest of OOC-PLWH in a medical home visit to facilitate their re-engagement in HIV care. Home visits could help DIS circumvent barriers to care re-engagement: privacy issues, impaired mobility and chronic health conditions, and by providing discreet and accessible medical care.MethodsFrom January to December 2017, DIS interviewed 847 OOC-PLWH and administered a questionnaire to ascertain their interest in a home visit to evaluate their general and HIV-related health status (e.g., physical and HIV evaluation, health education, sexually transmitted diseases [STD] and hepatitis C [HCV] screening).ResultsOf the 847 OOC-PLWH interviewed, 111 (13%) were interested in home visits. The majority of participants were male (69%), non-Hispanic black (60%) and had a median age of 47 years at intervention (range: 19–88). Thirty-eight percent were men who had sex with men. Higher proportions of those interested accepted care appointments (93% vs. 73%) and kept a clinic appointment (78% vs. 61%). Compared with non-Hispanic blacks, Hispanics were less likely to be interested in home visits (aOR: 0.59; 95% CI: 0.36–0.96). Compared with persons who accepted an HIV care appointment, persons who did not were significantly more likely to express interest in home visits (aOR: 4.18; 95% CI: 1.62–10.78). Those expressing general interest had specific interest in assessments for HIV-related blood tests (85%), medication (84%) or education (78%), as well as general health evaluation and screening for HCV (68%) or STD (64%).ConclusionOur assessment suggests that medical home visits could improve re-engagement rates among OOC-PLWH. Lower interest among Hispanic patients suggests that future efforts should be sensitive to community needs and concerns.Disclosures All authors: No reported disclosures.

Factors associated with viral non-suppression among adolescents living with HIV in Cambodia: a cross-sectional study

BackgroundAdolescents living with HIV on antiretroviral therapy (ART) have worse treatment adherence, viral suppression, and mortality rates compared to adults. This study investigated factors associated with viral non-suppression among adolescents living with HIV in Cambodia.MethodsA cross-sectional study was conducted in August 2016 among 328 adolescents living with HIV aged 15–17 years who were randomly selected from 11 ART clinics in the capital city of Phnom Penh and 10 other provinces. Clinical and immunological data, including CD4 count and viral load, were obtained from medical records at ART clinics. Adolescents were categorized as having achieved viral suppression if their latest viral load count was < 1000 ribonucleic acid (RNA) copies/mL. Multivariate logistic regression analysis was performed to identify factors independently associated with viral non-suppression.ResultsThe mean age of the participants was 15.9 years (SD = 0.8), and 48.5% were female. Median duration on ART was 8.6 (interquartile range = 6.0–10.6) years. Of total, 76.8% of the participants had achieved viral suppression. After adjustment for other covariates, the likelihood of having viral non-suppression remained significantly lower among adolescents who were: older/aged 17 (AOR = 0.46, 95% CI 0.21–0.98), had been on ART for more than 9 years (AOR = 0.35, 95% CI 0.19–0.64), had most recent CD4 count of > 672 (AOR = 0.47, 95% CI 0.26–0.86), had a relative as the main daily caregiver (AOR = 0.37, 95% CI 0.17–0.80), and did not believe that there is a cure for AIDS (AOR = 0.40, 95% CI 0.21–0.75) compared to their reference group. The likelihood of having viral non-suppression also remained significantly higher among adolescents who had first viral load > 628 RNA copies/mL (AOR = 1.81, 95% CI 1.05–4.08) and among those who were receiving HIV care and treatment from an adult clinic (AOR = 2.95, 95% CI 1.56–5.59).ConclusionsThe proportion of adolescents living with HIV with viral suppression in this study was relatively high at 76.8%, but falls short of the global target of 90%. Programs targeting younger adolescents and adolescents in transition from pediatric to adult care with a range of interventions including psychosocial support and treatment literacy could further improve viral suppression outcomes.

Effect of photodynamic therapy by 810 and 940 nm diode laser on Herpes Simplex Virus 1: An in vitro study.

Herpes simplex virus (HSV) is among the most common viruses in humans. HSV1 is often responsible for oral and perioral herpetic lesions. Photodynamic therapy (PDT) is a novel antimicrobial modality that involves the use of laser and a photosensitizer with a specific wavelength. This study aimed to assess and compare the effect of PDT with 810 and 940 nm diode laser and indocyanine green (ICG) photosensitizer on HSV1. In this in vitro study, HSV1 isolated from herpes labialis and there were 6 experimental groups.The irradiation parameters were the same for all groups. Number of remaining viruses per milliliter in each group was determined using real-time polymerase chain reaction (PCR) and statistically analyzed by ANOVA. The virus count in all groups significantly decreased compared to the control group (P < 0.05) except in group ICG- without irradiation (P > 0.05). Comparison of groups 810- and 940- (use of each laser alone) with groups 810+ and 940+ (use of each laser plus ICG) revealed that reduction in virus count in groups 810+ and 940+ was significantly greater than that in groups 810- and 940-. 810 nm diode laser irradiation and ICG causes the greatest reduction in number of HSV1 compared to all the other groups. ICG without laser irradiation has not significant efficacy on reduction of virus count.

The association between oral disease and type of antiretroviral therapy among perinatally HIV-infected youth.

This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

Study on acute HIV-1 infection in men who have sex with men in Tianjin

Objective: To understand the immunological and virological characteristics of HIV-1 infected men who have sex with men (MSM) in the acute phase in Tianjin and evaluate the effects of the fourth generation HIV ELISA and the P24 ELISA for acute HIV-1 infected samples. Methods: From October 2015 to October 2016, MSM were recruited through the community-based organizations in Tianjin. All the participants received rapid HIV test, positive samples were confirmed by Western Blot and negative samples underwent pooled nucleic acid testing. The participants with HIV-1 RNA reactive result underwent testing for viral load and T-cell count after second blood collection. Acute HIV-1 infection was defined as negative rapid HIV test result and the positive results of two HIV RNA tests, then the sensitivity were compared between the fourth generation HIV ELISA and the P24 ELISA to detect the initial HIV-1 RNA positive samples. Results: Among 3 016 MSM screened, 193 were positive in rapid HIV test. Western blot testing indicated that 179 cases were HIV positive, 7 cases were HIV indeterminate and 7 cases were negative. Of 2 823 sero-negative cases, 17 were acute HIV-1 infections. The HIV-1 infection rate was 6.53% (197/3 016) and the acute HIV-1 infection rate was 0.56% (17/3 016), with an average viral load of (5.63±1.50) log(10) copies/ml, an average CD(4) count of (442.82±268.17) cells/μl, an average CD(8) count of (1 069.65±668.22) cells/μl and an average CD(4)/CD(8) ratio of (0.49±0.25). Higher viral load, CD(4) and CD(4)/CD(8) ratio were seen in the acute HIV-1 infection group compared with the chronic HIV-1 infection group (U=148, P<0.01; U=272, P=0.042 and t=3.147, P=0.005). Demographic characteristics were similar between two groups, except the occupation (χ(2)=11.016, P=0.026). The sensitivity of P24 ELISA was higher than the fourth generation HIV ELISA in the HIV-1 detection for acute infection (Fisher's exact test, P=0.017). Conclusions: MSM are at risk for acute HIV-1 infection. Screening for acute HIV-1 infection with P24 ELISA would increase the sensitivity of diagnosis and reduce HIV transmission in MSM.

HIV Outcomes for Foreign-Born Patients Receiving Care at a Safety Net County Health System in the Southern US

Background: Foreign-born Human Immunodeficiency Virus (HIV) infected patients receiving care in the US have complex factors affecting their care outcomes. Methods: We analyzed viral suppression, CD4 count, and healthcare retention among foreign-born patients from non-Spanish speaking countries in a publicly funded health system in Dallas, Texas through a retrospective chart review from 2010 to 2016. Results: Foreign-born patients had a viral suppression rate of 79*3%. Unsuppressed viral load, CD4 counts less than 200, and loss to care were significantly associated with higher emergency room (ER) visits and hospital admissions. Lack of healthcare coverage (excluding Ryan White coverage) and missed primary care appointments were significantly associated with unsuppressed viral load and loss to care. In multivariate logistic regression, having Ryan White coverage made one less likely to be lost to care than other health care coverage options (OR 0*309). Interpretation: This study revealed that, factors related to healthcare utilization like ER visits, hospital admissions, and lack of healthcare coverage had a negative impact on HIV outcomes rather than socio-cultural factors like region of origion or language. Ryan White coverage, a payer of last resort in Texas, was predictive of retention in care of foreign-born patients in this area. Funding Statement: The authors declare None. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the University of Texas, Southwestern Medical Center Institutional Review Board.

A Markov Model to Estimate Mortality Due to HIV/AIDS Using Viral Load Levels-Based States and CD4 Cell Counts: A Principal Component Analysis Approach.

IntroductionImprovement of health in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients on antiretroviral therapy (ART) is characterised by an increase in CD4 cell counts and a decrease in viral load to undetectable levels. In modelling HIV/AIDS progression in patients, researchers mostly deal with either viral load levels only or CD4 cell counts only, as they expect these two variables to be collinear. In this study, both variables will be in one model.MethodsPrincipal component variables are created by fitting a regression model of CD4 cell counts on viral load levels to improve the efficiency of the model. The new orthogonal covariate is included to represent the CD4 cell counts covariate for the continuous time-homogeneous Markov model defined. Viral load levels are categorised to define the states for the Markov model.ResultsThe likelihood ratio test and the estimated AICs show that the model with the orthogonal CD4 cell counts covariate gives a better prediction of mortality than the model in which the covariate is excluded. The study further revealed high accelerated mortality rates from undetectable viral load levels as well as accelerated risks of viral rebound from undetectable viral level for patients with lower CD4 cell counts than expected.ConclusionInclusion of both viral load levels and CD4 cell counts, monitoring and management in time homogeneous Markov models help in the prediction of mortality in HIV/AIDS patients on ART. Higher CD4 cell counts improve the health and consequently survival of HIV/AIDS patients.

Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is dampened in HIV exposed

Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T-cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy controls (HCs; n = 14). Among UHIVs, those with CD4+ <500 cells/mm3 presented the lowest significant CE, HDL cholesterol (HDL-C), and ApoAI levels. ECs showed similar HDL-C, ApoAI, and CE compared with HCs. Among UHIVs, CE positively correlated with CD4+ T-cell counts (Beta: 1.05; 95% CI: 1.02; 1.07), and for VL higher than 3.8 log, CE was inversely associated with VL (Beta: 0.70; 95% CI: 0.51; 0.95). Remarkably, HESNs presented higher CE (0.78 ± 0.14) than UHIVs (0.65 ± 0.17; P = 0.0005), but lower than HCs (0.90 ± 0.13; P = 0.009). hsCRP levels were highest in the UHIV group (0.45 ± 0.49). CE was sensitive to HIV disease progression. Low CE in HIV patients was associated with lower CD4+ T-cells and higher VL and hsCRP. CE was also lower in HESNs compared with HCs. Our results suggest that immune status secondary to HIV progression and exposure influence plasma HDL-CE capacity.

Smooth control of HIV/AIDS infection using a robust adaptive scheme with decoupled sliding mode supervision

In this paper, a robust adaptive controller subject to decoupled sliding mode controller as a supervisory controller has been implemented on the HIV infection dynamic model. A five-state dynamic model of HIV is utilized which the measurement of the CD4+T cells and the viral load counts are necessary to estimate all its parameters. Decoupled sliding mode control is a variable structure controller having significant and appropriate features, such as best tracking and regulation performance and robustness and elevate the performance of the controller. Generally, due to the importance of applied treatment strategy to mitigate viral escape, sliding mode control is utilized in accordance with PI control to deliver necessary control inputs. To achieve the least possible chattering, effectual methods such as the transfer function is used. To update the gains of PI control, an adaptation law is then employed. The results demonstrate the suitable performance of the controller via providing proper tracking performance, and also, elimination of the chattering problem and decrease the time of treatment. The number of infected CD4+ T-cells and the number of free virus particles can be controlled in less than five days. The proposed controller is capable of controlling the dynamic behavior of the virus concentration for different patients with the same control scheme.

Spotlight on … infection in obstetrics and gynaecology

Spotlight on … infection in obstetrics and gynaecology

The favorable effects of KIR3DS1 and Bw4(80Ile) on viral set point and CD4 count decline in HIV-1 patients with acutely infected with HIV-1 infection

Objective: To investigate whether killer cell immunoglobulin-like receptor 3DS1(KIR3DS1)and Bw4(80Ile) could play a protective role during HIV-1 infection. Methods: KIR3DL1/3DS1 and Bw4, Bw6 were genotyped by SSP-PCR and Bw4 allotypes (Bw4(80Ile) and Bw4(80Thr))were classified via sequencing among 109 individuals acutely infected with HIV-1 in Beijing You'an Hospital between 2006 and 2012. Results: (1)Of the 109 patients, 65, 7, and 37 subjects respectively harbored KIR3DL1/KIR3DL1, KIR3DS1/KIR3DS1, and KIR3DL1/KIR3DS1 genotypes. Their viral set points were determined as 4.35±0.79, 4.24±0.49 and 3.99±0.85 respectively. The viral set point of patients carrying KIR3DL1/KIR3DS1 was significantly lower than the KIR3DL1/KIR3DL1 genotype patients (P=0.032). (2)26, 41, 42 subjects harbored Bw4(80Ile,) Bw4(80Thr,) Bw6/6, respectively. Viral set points of these subjects were respectively 3.89±0.49, 4.20±1.03 and 4.44±0.59.One-way ANOVA indicated that Bw4(80Ile)influenced the levels of viral set point(P=0.027). Moreover, the level of viral set point of the Bw4(80Ile) genotype was significantly lower than the Bw6/6 genotype (P=0.020). These outcomes indicated Bw4(80Ile) was associated with lower levels of viral set point.(3)Viral set point of patients harboring KIR3DS1 and Bw4(80Ile)was 3.26±0.81 and significantly lower than individuals possessing other genotypes (all P<0.05). KIR3DS1 and Bw4(80Ile) conferred an advantage over other genotypes, especially over KIR3DS1 and Bw6/6 (P=0.006), KIR3DL1 and Bw6/6 (P=0.015) and even KIR3DL1 and Bw4(80Ile) (P=0.019 6) in delaying CD4 count decline within 3 years after HIV-1 infection. Conclusions: KIR3DS1 and Bw4(80Ile) are synergistically related to lower viral set point and slowing down the CD4 count decline as Bw4(80Ile) in the presence of KIR3DS1.

Effect of Rainfall on the Microbial Water Quality of a Tropical Urban Catchment.

Wet weather conditions have been associated with increased bacterial and viral counts in surface waters. Moreover, heavy rainfall and flooding were found to be the most common events preceding waterborne disease outbreaks associated with extreme weather conditions. This study aimed to examine the effect of rainfall on the quality of surface waters and to determine its suitability for primary contact recreation during wet weather conditions. A total of 228 catchment water samples were collected during wet and dry periods. Parameters that were found to increase with increasing rainfall were , enterococci, somatic coliphages, and turbidity, whereas total dissolved solids were found to decrease. Positive correlations ( < 0.05) were observed between cumulative rainfall and geometric mean concentrations of , enterococci, somatic coliphages, and turbidity ( = 0.69-0.95), whereas a negative correlation was observed between cumulative rainfall and total dissolved solids ( = -0.58). In addition, a rapid decline in water quality was observed during heavy rainfall that resulted in failure to meet recreational water quality guidelines. In view of public health and safety, primary recreational activities in the water catchment may not be advisable during or immediately after a rainfall event due to poor water quality.

Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population. AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m3 . Cox proportional hazards models were used to assess risk factors for CKD, which included key patient demographic data and antiretroviral therapy (ART) exposure. Of 1924 patients included in the analysis between April 2008 and March 2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60 mL/min per 1.73 m3 through two consecutive eGFR measurements at least 3 months apart). Of the examined risk factors, baseline age, baseline eGFR, and the route of HIV acquisition were statistically significant predictors of development of CKD. ART exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte count were not found to be significant risk factors for CKD. This is the first study to investigate the risk factors for development of CKD among Australian HIV-infected patients using cohort data. It highlights the need for awareness of renal risk factors, particularly among older patients or in those with pre-existing renal dysfunction. Further research is required to explore the discrepancy between patients who have acquired HIV through different means of exposure.

Evaluation of non-treponemal tests (VDRL) in the cerebrospinal fluid (CSF) in patients with HIV/AIDS at Instituto de Infectologia Emilio Ribas, São Paulo, Brazil

Background: The prevalence of Syphilis has been increasing in the general population and also in patients with HIV/AIDS, and consequently the occurrence of neurosyphilis. Methods & Materials: We reviewed all non-treponemal tests (CSF-VDRL) performed during the period of January, 2013 to September, 2014 and identified 154 patients with neurosyphilis. A total of 135 patients were included in this study after the exclusion of 19 patients due to the lack of viral load and CD4 assessments at the time of the diagnosis of neurosyphilis. We also assessed CSF cytotogy and chemical analysis, HIV RNA (viral load) and CD4 T lymphocyte (CD4) cell count. Results: The analysis showed a total of 135 patients with reactive CSF-VDRL (1:2 a 1:1024). Most patients were men 97.77 (132/135) and the mean age was 43 y (20-64). 39 patients (28.89%) presented CD4 count < 350 cells/mL, of which 19 subjects (48.72%) had HIV viral load below the assay's limit of detection (undetectable) and mean cell count of 9.89 (0-81) whereas 20 subjects (51.28%) presented HIV viral load > 40 copies/mL and mean cell count of 8.96 (0-40). 96 subjects (71.11%) presented CD4 count > 350 cells/mL, of which 83 had undetectable viral load and mean cell count of 7.68 (0-360) and 13 had viral load above the assay's limit of detection and mean cell count of 10.76 (0-55). Conclusion: Our data showed the occurrence of neurosyphilis in 71.1% of HIV/AIDS subjects with CD4 count > 350 cells/mL.

Impact of schistosome infection on long-term HIV/AIDS outcomes

BackgroundAfrica bears the burden of approximately 70% of global HIV infections and 90% of global schistosome infections. We sought to investigate the impact of schistosome infection at the time of HIV-1 seroconversion on the speed of HIV-1 disease progression, as measured by the outcome CD4+ T-cell (CD4) counts <350 cells/μL and/or death. We hypothesized that people who had been infected with Schistosoma spp. at the time they acquired HIV-1 infection would have impaired antiviral immune response, thus leading them to progress twice as fast to a CD4 count less than 350 cells/μL or death than would people who had been free of schistosomes at time of HIV-1 seroconversion.Methods and principal findingsWe conducted a longitudinal study in Tanzania from 2006 to 2017 using stored blood spot samples, demographic surveillance and sero-survey data from the community, and a review of clinical charts. A competing risk analysis was performed to look at the difference in time to reaching CD4 counts < 350 cells/μL and/or death in HIV-1-infected people who were infected versus not infected with Schistosoma spp. at time of HIV-1 seroconversion. We found an 82% reduction in risk of reaching the outcome in seroconverters who had been infected with Schistosoma (subHazard Ratio = 0.18[0.068,0.50], p = 0.001) after adjusting for age, occupation, clinic attendance and time-dependent covariates.ConclusionsOur study demonstrates that people with schistosome infection at the time of HIV-seroconversion develop adverse HIV outcomes more slowly than those without. The findings are contrary to our original hypothesis. Our current longitudinal findings suggest complex interactions between HIV-1 and schistosome co-infections that may be modulated over time. We urge new immunological studies to investigate the long-term impact of schistosome infection on HIV-1 viral load and CD4 counts as well as related immunologic pathways.