Load Rebound Research Articles

Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection

Abstract Background Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug. Methods Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and post-treatment. Results Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n=241) received valganciclovir or maribavir for at least 21 days (median 55-56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35-125 days (median 56) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66-110 days (median 90). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after re-treatment with an alternative CMV antiviral drug. Conclusion After 3-8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy. Clinical Trials Registration NCT02927067 (AURORA)

Optimal demand response for a virtual power plant with a hierarchical operation framework

There are significant uncertainties and variations in demand response under different operating conditions and incentives. These challenges hinder virtual power plants (VPPs) from fully leveraging the regulatory capabilities of flexible resources. To address this issue, this study introduces an optimal demand response (DR) approach for VPPs, featuring a hierarchical operational framework that accounts for the uncertainty in user participation in DR. First, a refined DR model is developed, incorporating response characteristic parameters based on the DR mechanism. Second, a two-stage distributionally robust optimization model is formulated within a market trading framework for energy scheduling of VPPs. This model aims to minimize operational costs while considering uncertainties in DR. Additionally, the ambiguity set for the uncertainty probability distributions is constructed using a data-driven method. Finally, the study presents an optimal DR disaggregation method that aims to maximize aggregator satisfaction and accounts for the impact of load rebound on the optimization results. Simulation results demonstrate that the proposed method significantly reduces the deviation in demand response by 40 % and enhances the profit of the VPP by 20.7 %.

Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

Real-world effectiveness of molnupiravir, azvudine and paxlovid against mortality and viral clearance among hospitalized patients with COVID-19 infection during the omicron wave in China: A retrospective cohort study

ObjectivesIn this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in hospitalized patients with COVID-19 in China dominated by the omicron BA.5.2 and BF.7 subvariant of SARS-CoV-2. MethodsEnrolled patients were assigned to the molnupiravir group or the azvudine group or the paxlovid group or the control group (not taking any antiviral drugs). The primary outcome of the cohort study was viral clearance and viral burden rebound after treatment and the secondary outcome was 28-day all-cause mortality. The four groups were propensity score-matched (1:1). We plotted viral load trends for each antiviral drug intervention using locally weighted regression (LOWESS) smoothed data. Multivariate logistic regression (stepwise algorithm) models were used to determine any risk factors for 28-day mortality. ResultsOf the 1537 patients receiving any treatment, 886 (57.6 %) received molnupiravir, 390 (25.4 %) received azvudine, 94 (6.1 %) received paxlovid, and 167 (10.9 %) did not use any antiviral drugs. Our data analysis showed that age (OR = 1.05, 95 % CI: 1.03-1.07, P < 0.001), Charlson comorbidty index (OR = 1.32, 95 % CI: 1.18-1.48, P < 0.001), severity of COVID-19 (P < 0.001), gamma globulin (OR = 2.04, 95 % CI: 1.03-3.99, P = 0.039) and corticosteroids use (OR = 2.3, 95 % CI: 1.19-4.69, P = 0.017) were independent prognostic factors for 28-day mortality in COVID-19 patients. After propensity score matching (PSM), the paxlovid recipients (OR = 0.22, 95 % CI: 0.05–0.83, P = 0.036) or azvudine recipients (OR = 0.27, 95 % CI: 0.07-0.91, P = 0.046) had lower 28-day mortality compared to their matched controls. Viral rebound occurred in the control group around days 9-16, while no viral rebound was found in any of the three oral antiviral groups. We found that molnupiravir group performed comparably in terms of the rate of nucleic acid conversion negative compared with the paxlovid group, while azvudine group performed slightly worse compared with the paxlovid group or molnupiravir group. ConclusionsIn our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.

Changes in access to viral load testing, incidence rates of viral load suppression and rebound following the introduction of the 'universal test and treat' guidelines in Cameroon: A retrospective follow-up analysis.

Cameroon adopted and started implementing in 2016, the 'universal test and treat' (UTT) guidelines to fast-track progress towards the 95-95-95 ambitious targets to end the HIV epidemic. Achieving the third 95 (viral load suppression) is the most desirable target in HIV care. We aimed to evaluate the effectiveness of this novel approach on access to viral load testing (VLT), viral suppression (VLS), and viral load rebound (VLR). A retrospective cohort study was conducted at The Nkongsamba Regional Hospital to compare VLT outcomes between the pre-UTT (2002 to 2015) and the post-UTT (2016 to 2020) periods. We used a data extraction form to collect routine data on adult patients living with HIV. We measured uptake levels of the first and serial VLT and compared the incidence rates of VLS (VL<1000 copies/ml) and viral load rebound (VLR) before and after introducing the UTT approach using Kaplan Meier plots and log-rank tests. Cox regression was used to screen for factors independently associated with VLS and VLR events between the guideline periods. Access to initial VLT increased significantly from 6.11% to 25.56% at 6 months and from 12.00% to 73.75% at 12 months before and after introducing the UTT guidelines respectively. After a total observation time at risk of 17001.63 person-months, the UTT group achieved an incidence rate of 90.36 VLS per 1000 person-months, four-fold higher than the 21.71 VLS per 1000 person-months observed in the pre-UTT group (p<0.0001). After adjusting for confounding, the VLS rate was about 6-fold higher in the UTT group than in the pre-UTT group (adjusted Hazard Rate (aHR) = 5.81 (95% confidence interval (95%CI): 4.43-7.60). The incidence of VLR increased from 12.60 (95%CI: 9.50-16.72) to 19.11 (95%CI: 14.22-25.67) per 1000 person-months before and after the introduction of UTT guidelines respectively. After adjusting, VLR was more than twice as high in the UTT group than in the pre-UTT group (aHR = 2.32, 95%CI: 1.30-4.13). Increased access to initial VLT and higher rates of VLS have been observed but there are concerns that the suppressed viral load may not be durable since the introduction of the UTT policy in this setting.

COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment

With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Optimal strategy to reduce energy waste in an electricity distribution network through direct/indirect bulk load control

In recent decades, the ever-increasing demand for electricity in large cities is leading the electricity distribution network (EDN) to an operational state of fatigue, especially at peak load times. In this context, load congestion, technical losses, and voltage deviations across the EDN can contribute to the high waste of electricity as well as to the worsening of the supply service. To face this problem, this paper proposes a mixed integer linear programming (MILP) model that aims to reshape the demand profile (i.e., load reduction in peak periods without load rebound in the remaining periods of the day) of total consumers while the voltage deviations and technical losses are minimized. In the proposed model, the demand profile reshaping is carried out through direct (DC) and indirect (IC) bulk control of residential, commercial, and industrial loads, while the load factor (LF), i.e., indicator related to the efficient use of electricity, is improved. Due to the scheduling of these loads at certain times of the day, the occurrence of voltage deviations and technical losses can be mitigated by the efficient control of capacitor banks (CBs). To corroborate the applicability of the proposed MILP model, the 33-node IEEE test system was used. The results show the technical and economic gains for the distribution company (DISCO) and the total number of consumers.

Dynamic heterogeneity in COVID-19: Insights from a mathematical model.

Critical illness, such as severe COVID-19, is heterogenous in presentation and treatment response. However, it remains possible that clinical course may be influenced by dynamic and/or random events such that similar patients subject to similar injuries may yet follow different trajectories. We deployed a mechanistic mathematical model of COVID-19 to determine the range of possible clinical courses after SARS-CoV-2 infection, which may follow from specific changes in viral properties, immune properties, treatment modality and random external factors such as initial viral load. We find that treatment efficacy and baseline patient or viral features are not the sole determinant of outcome. We found patients with enhanced innate or adaptive immune responses can experience poor viral control, resolution of infection or non-infectious inflammatory injury depending on treatment efficacy and initial viral load. Hypoxemia may result from poor viral control or ongoing inflammation despite effective viral control. Adaptive immune responses may be inhibited by very early effective therapy, resulting in viral load rebound after cessation of therapy. Our model suggests individual disease course may be influenced by the interaction between external and patient-intrinsic factors. These data have implications for the reproducibility of clinical trial cohorts and timing of optimal treatment.

Factors associated with viral suppression and rebound in children and adolescents living with HIV on antiretroviral treatment at the Bangui pediatric complex, Central African Republic

Background: Suppression of viral load and its maintenance is the necessary condition for reducing mortality linked to HIV infection in children. This study aimed to investigate the factors associated with viral load rebound in children receiving antiretroviral treatment. Methods: This was a cross-sectional study with analytical purposes, running from August 1 to 31, 2023. Were inclusive, all children living with HIV under 15 years of age, with at least two viral load results and whose parents have agreed to participate in the study. Results: A total of 286 children were included in the study. The mean age was 11.5 years (±2.8). More than half (55.2%) of the children were not informed of their HIV status and for the majority (50.3%). Among the 198 children with a suppressed viral load at the first test, 46 (23.2%) experienced a rebound in viral load at the last test. The factors significantly associated with rebound were the low level of education of the parents (p=0.012), the administration of medicines to the children by the parents (p=0.000), the long duration of taking the medicines (p=0.021) and poor compliance with treatment (0.000). Conclusions: The rebound in viral load after suppression is a disastrous reality for children. Efforts must be made to strengthen early therapeutic education for children, training of health workers on the process of announcing results and ongoing dialogue with children and adolescents on compliance are ways to improve the maintenance of viral suppression.

930. COVID-19 symptom and viral load rebound among individuals reporting nirmatrelvir/ritonavir use compared to propensity score matched individuals not taking COVID-19 treatment

930. COVID-19 symptom and viral load rebound among individuals reporting nirmatrelvir/ritonavir use compared to propensity score matched individuals not taking COVID-19 treatment

Symptoms, Viral Loads, and Rebound Among COVID-19 Outpatients Treated With Nirmatrelvir/Ritonavir Compared With Propensity Score-Matched Untreated Individuals.

Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals. We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated. Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7). Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients.

Low-carbon demand response strategy of buildings considering load rebound

With the carbon emission ratio of buildings increasing, including buildings in the carbon market, an inevitable trend of social development is created. Buildings are characterized by their strong seasonality, high simultaneity rate, and large load, which is not only the main factor leading to the peak load of a power grid but also an important resource for load control. Under the guidance of dynamic carbon emission prices and real-time electricity prices, it is worth considering how best to balance the peak response ability of buildings and the cause of the secondary peak leading to load rebound. Therefore, this paper proposes a low-carbon demand response strategy for buildings considering load rebound. First, a building load is classified based on how schedulable the load remains, and a building demand response model which considers how the load schedulability is constructed. Second, according to the different rebounds of different building loads, a load rebound optimization model based on linear attenuation was built, and the rebound parameters of various loads were designed. Then, the real-time carbon emission factor, load fluctuation reward, punishment factor, and real-time electricity price are introduced. Thus, the lowest running cost of the building load is taken as the objective function needed to construct a building demand response optimization model while also considering load rebound. Finally, an example analysis is used to verify the effectiveness of the proposed model in reducing the comprehensive operation cost of buildings. The proposed model not only effectively reduces the comprehensive operation cost of buildings, but also reduces carbon emissions and load fluctuations under the premise of satisfying the actual building load, which provides a new idea for the research of a low-carbon demand response strategy of buildings with load rebound.

Alternative dolutegravir dosing strategies with concurrent rifapentine utilized for latent tuberculosis treatment.

We present a case of a 53-year-old person living with human immunodeficiency virus and a new diagnosis of latent tuberculosis. The patient had baseline suppressed HIV viral load on fixed dose combination dolutegravir/abacavir/lamivudine when once-weekly rifapentine 900mg/isoniazid 900mg/pyridoxine 25mg was initiated for 12weeks. An additional 50mg dolutegravir dose, administered in the evenings, was added to the daily antiretroviral regimen for treatment duration secondary to rifapentine uridine diphosphate glucuronsyl transferase induction. Dolutegravir trough concentrations decreased during concurrent therapy with noted slight HIV viral load rebound. Upon completion of rifapentine use, and a return to dolutegravir 50mg daily dose, the trough concentrations increased with a return to an undetectable viral load. We provide suggested dolutegravir dosing considerations with concomitant rifapentine use, not currently addressed in recommended guidelines.

Load rebound suppression strategy and demand response potential of thermal storage HVAC systems: An experimental and simulation study

The problem of power imbalance caused by the large power consumption of heating, ventilation and air-conditioning (HVAC) units in the summertime can be alleviated by building demand response (DR) strategies. However, after DR, load rebound will occur due to the sudden increase in demand. Meanwhile, there is a general lack of information on effective DR strategies. To study the DR potential and load rebound suppression strategies of HVAC systems, nine operation strategies were devised and applied experimentally. The physical experiments were conducted on a central air-conditioning system to investigate control strategies such as regional temperature reset, active energy storage, cold source unit activation and deactivation, as well as pre-cooling. Additionally, a simulation model was developed utilizing TRNSYS. DR evaluation indices, such as duration, power reduction capability, system operation cost, etc. were applied. The experimental results show that after a water storage tank is added as a buffer tank, the start and stop times of the air source heat pump were reduced from 46 to 6. Utilizing the thermal inertia of building and HVAC system, while ensuring personnel's thermal comfort, the DR participation time can be extended to 40–50 min. This will result in an 8.9 %–12.6 % reduction in power consumption. The simulation results show that with active energy storage added, HVAC system's DR participation time can be increased to about 120 min, the maximum power consumption can be reduced by 23.4 %, and the maximum operating cost can be reduced by 21.7 %. The study shows that a slow recovery strategy and the extension of DR control time can limit load rebound effectively. From the result of load rebound suppression effect, if the load rebound suppression strategy is not adopted, the power after DR will be 3.7 % higher than that pre-DR; the load rebound suppression strategy is adopted, which is 3.6 % lower than that pre-DR. By implementing the proposed DR strategies, the issue of frequent activation and deactivation of refrigeration units can be effectively mitigated. This will greatly alleviate the power supply and demand contradiction, while also effectively suppressing the load rebound effect to prevent a secondary peak in power consumption.

Viral rebound and safety of nirmatrelvir/ritonavir for lung-transplant recipients infected with SARS-CoV-2

Data on the viral rebound and safety of nirmatrelvir/ritonavir in lung transplant (LTx) recipients are limited. The study prospectively followed four LTx recipients. Clinical characteristics, viral RNA dynamic in throat swabs, and tacrolimus blood concentration were monitored regularly. All four LTx recipients, aged 35–74 years, were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They got coronavirus disease 2019 (COVID-19) after more than one week of admission during the era of Omicron. All cases received nirmatrelvir/ritonavir (NM/r) within two days of infection, and the relative viral RNA copies dropped quickly. Viral load rebound was observed in all four cases after discontinuation of the first five days of NM/r treatment. Three of them received another 5-days antiviral therapy with NM/r. The duration of positive viral PCR testing was 25-28 days. None of them progressed into severe or critical COVID-19. Tacrolimus was stopped 12 h before NM/r and held during the 5-day course of antiviral therapy. Blood concentration of tacrolimus were maintained at a baseline level during these five days. Tacrolimus was re‐initiated at its baseline daily dose 3-4 days after NM/r therapy. However, during the second round of antiviral therapy with NM/r, the concentration of tacrolimus fluctuated wildly. In conclusion, the 5-day course of NM/r treatment was not sufficient for LTx recipients and the viral rebound was common. More data are needed to clarify whether LTx recipients with SARS-CoV-2 viral rebound could benefit from additional treatment with NM/r.

Virtual energy storage system for peak shaving and power balancing the generation of a MW photovoltaic plant

This article proposes a novel control of a Virtual Energy Storage System (VESS) for the correct management of non-programmable renewable sources by coordinating the loads demand and the battery storage systems operations at the residential level. The proposed novel control aims at covering two main gaps in current state-of-the-art VESSs. The first gap is considering a distributed battery storage system instead of a centralized one, the second gap is providing the electricity grid operator with two services instead of one. To this aim, the authors explore a VESS consisting of residential buildings where each apartment is equipped with an air conditioner but also with a battery storage system. The explored VESS provides the grid operator with both peak shaving and power balancing services for the generation of a megawatt photovoltaic plant located near the VESS. The goodness of the proposed coordinated control is demonstrated via numerical experiments and using real data, measured every 15 min in September 2019. The case study consists of a 1.4 MW photovoltaic plant located near a small town, 21 residential buildings with 168 apartments, each equipped with an air conditioner (continuous power is 1.5 kW) and battery energy storage systems (3 kW /2.5 kWh). The numerical results show that the battery energy storage systems are charged correctly during peak hours (the charging power is between 0.45 and 0.90 kW, and the state of charge varies from 20 % to 78 %) and that the residual photovoltaic plant generation resembles a horizontal line. Later, in the early afternoon, the reference temperature of the air conditioners and the charge/discharge of the battery storage systems are suitably adjusted by solving a mixed linear integer programming problem, to balance the reduction in photovoltaic plant generation, which lasts an hour and a half and peaks at 188 kW. Finally, the numerical results also show that the energy that remained in the batteries is entirely consumed by users in the late afternoon or evening and that the amplitude and the duration of the so-called “load rebound” are so slight that no compensation action (e.g., the bath returning or linear recovery strategy) is required for the considered case study.

Influence of Measurement Uncertainty in the Determination of Selected Rock Parameters-A Realistic Approach.

To determine and compare the measurement uncertainty of different geological-geotechnical testing methods, numerous test locations were selected in a hard rock quarry. Measurements were carried out along two vertical measurement lines perpendicular to the mining levels of an existing exploration. Along these lines, the rock quality basically varies due to weathering (decreasing influence with increasing distance from the original ground surface), but also due to the influence of the geological-tectonic conditions on site. The mining conditions (blasting) are identical over the considered area. The rock quality was examined as follows: as field tests, the rock compressive strength was determined by means of point load test and rebound hammer, as laboratory method the Los Angeles test (standard laboratory test for the determination of the mechanical rock quality) was used to identify the impact abrasion resistance. The statistical evaluation and comparison of the results allowed conclusions to be drawn about the contribution of the individual test methods to the measurement uncertainty whereas, in practice, a priori information can be applied complementarily. It shows that the influence on the combined measurement uncertainty u of the different methods due to the geological variability in horizontal direction reaches values between 17 and 32%, whereby the rebound hammer method shows the highest values. However, the highest influences on the measurement uncertainties are a result of the vertical direction due to weathering phenomena with percentages of 55 to 70%. For the point load test, the vertical direction shows the highest significance with an influence of approximately 70%. This leads to the conclusion that a higher weathering degree of the rock mass shows an increasing effect on the measurement uncertainty which needs to be considered using a priori information in measurements.

Controversies in the Design of Strategies for the Cure of HIV Infection.

The cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the viral load rebounds when the treatment is discontinued, leading to disease progression. There are several theories and hypotheses about the biological foundations that prevent a cure. The main obstacle appears to be the existence of a latent viral reservoir that cannot be eliminated pharmacologically. This concept is the basis of the new strategies that seek a cure, known as kick and kill. However, there are other lines of study that recognize mechanisms of persistent viral replication in patients under effective treatment, and that would modify the current lines of research on the cure of HIV. Given the importance of these concepts, in this work, we propose to review the most recent evidence on these hypotheses, covering both the evidence that is positioned in favor and against, trying to expose what are some of the challenges that remain to be resolved in this field of research.

A prospective study of predictors of HIV viral load rebound in an HIV hyperendemic rural population of KwaZulu-Natal, South Africa

A prospective study of predictors of HIV viral load rebound in an HIV hyperendemic rural population of KwaZulu-Natal, South Africa

1411. Missed HIV Clinic Visits among Youth Living with HIV in Alabama

Abstract Background Adolescents and young adults with HIV consistently account for about one-fifth of new infections in the United States. YLWH have lower rates of testing, diagnosis, treatment engagement, and viral suppression than adults with HIV. YLWH are particularly challenged with missing medical appointments. Few studies have been published on youth living with HIV (YLWH)’s missed clinic visits and risk factors. Therefore, this study was designed to explore: 1). if the missed visits have significant associations with HIV treatment outcomes (more than 50 counts of CD4 counts drop, viral load increment, and viral suppression) in YLWH; 2). What factors are associated with missed visits for YLWH? 3) Are these factors different from the risk factors of all PLWH? Methods A retrospective study using data records from UAB Family Clinic was designed. The study used the records from March 1st 2020 to August 31st, 2021. Patients aged 16-24 were considered as YLWH. The primary outcomes are missed visits and treatment outcomes. CD4 change, Viral suppression and VL change during the study period were investigated for identifying the association between missed visit and treatment outcome. Age, gender, race, HIV transmission mode, insurance type and the viral suppression in index record were used as factors to predict missed visits. Chi-square test and logistic regression have been conducted in SAS 9.4. Results YLWH with missed visits had more viral load rebound compared to those without missed visits (p=0.04). For YLWH, gender and viral suppression in the index record have significant associations with missed visits (Gender: p=0.03, Viral suppression in index record: p=0.04). In tests among all PLWH, Race (p=0.03), Insurance type (p=0.01) and viral suppression in index record (p=0.001) are associated with missed visits. Table 1.Viral load change by missed visits.Table 2.Risk factors associated with missed visits among YLWH (n=101).Table 3.Risk factors associated with missed visits among PLWY (n=296). Conclusion Missed visits are significantly associated with viral load maintenance, and missed visits have adverse effects on treatment outcomes. Also, the risk factors for YLWH of missed visits are not identical with the risk factors for PLWH from the same cohort. Disclosures All Authors: No reported disclosures.