Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials - United States and International Sites, 2021-2022.

Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most reports are based on individual cases or nonrandomized studies. Viral RNA shedding data from two phase 2/3, randomized, double-blind, placebo-controlled clinical trials of nirmatrelvir/ritonavir (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients [EPIC-HR] and Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients [EPIC-SR]) were analyzed to investigate the role of nirmatrelvir/ritonavir treatment in COVID-19 rebound.

Long-Acting Formulations for the Prevention and Treatment of Human Immunodeficiency Virus (HIV)-1 Infection: Strategic Leveraging and Integration of Multidisciplinary Knowledge to Advance Public Health.

The landscape for the development of therapeutics for prevention and treatment of human immunodeficiency virus (HIV)-1 infection has pivoted towards long-acting antiretrovirals (LA-ARVs). LA-ARVs have the potential to transform global implementation of HIV-1 prevention and treatment strategies. The ability to identify potential knowledge gaps early in development, proactively address missing information or data gaps, and strategically leverage all the available information is the key to streamline the development of safe and effective LA-ARV therapeutics.

Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective.

Purpose Of Review: Outline some regulatory considerations and scientific challenges related to the development of long-acting antiretrovirals (ARVs) for the treatment and prevention of HIV-1 infection.

Recent Findings: Poor adherence to oral ARV regimens continues to pose challenges for effective treatment and prevention of HIV-1 infection. The development of long-acting ARV modalities for treatment and prevention of HIV-1 infection is emerging as a promising alternative to the current treatment and prevention paradigm and has gained considerable interest.

Deep sequencing prompts the modification of a real-time RT-PCR for the serotype-specific detection of polioviruses.

Polioviruses are members of the Enterovirus C species and asymptomatic fecal shedding allows for their transmission and persistence in a community, as well as the emergence of vaccine-derived polioviruses. Using three serotype-specific real-time RT-PCR (rRT-PCR) assays, the shedding and circulation of oral poliovirus vaccine (OPV) strains was previously investigated in a prospective cohort of Mexican children, their contacts, and nearby sewage. Subsequently, a deep sequencing approach targeting the P1 genomic region was applied to characterize OPV strains previously detected by rRT-PCR.

Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico.

Background: Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015.

Objectives: To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts.

Materials And Methods: We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz.

Detection of Emerging Vaccine-Related Polioviruses by Deep Sequencing.

Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants.

Human T-lymphotropic Virus Co-infections in Adults Infected With Human Immunodeficiency Virus.

Introduction: Human T-lymphotropic virus type 1 or 2 (HTLV-1/2) co-infection in patients infected with the human immunodeficiency virus (HIV) can lead to increased morbidity. Because HTLV-1/2 shares a similar transmission route with HIV, HTLV-1/2 infection may be more prevalent in HIV-infected individuals. However, rates of HTLV-1/2 co-infection among HIV-infected individuals have not been studied recently in the United States.

CD4 Count Recovery After Initiation of Antiretroviral Therapy in Patients Infected With Human Immunodeficiency Virus.

Background: Prognosis for patients infected with human immunodeficiency virus (HIV) correlates with levels of CD4+ T cells. Initiation of antiretroviral therapy (ART) interrupts multiple points in the virus life cycle, causing an increase in CD4 cells. The rate at which the CD4 count recovers is highly variable and subject to influence by many factors.

Determinants of Elevated Alkaline Phosphatase in Patients Infected with HIV.

Objectives: A retrospective cross-sectional study was performed to assess the prevalence of elevated alkaline phosphatase (ALP) in patients infected with human immunodeficiency virus (HIV) and to determine the relation between ALP and specific antiretroviral therapy (ART).

Methods: A total of 2990 patients were included in this study. Data were collected from a major academic institution's HIV clinic using the most recent searchable values from patients' medical records.

Effects of Well-Controlled HIV Infection on Complement Activation and Function.

Introduction: Uncontrolled HIV infection is known to activate the complement system, leading to an increase in chronic inflammation. Whether or not this activation of complement persists and contributes to chronic inflammation in subjects with HIV infection that is well controlled through use of antiretroviral therapy has not been studied.

Methods: We conducted an observational, cross-sectional study using sera from 305 adults with well-controlled HIV infection and 30 healthy controls.

Association of time since pneumococcal polysaccharide vaccine receipt and CD4 count with antibody response to the 13-valent pneumococcal conjugate vaccine in HIV-infected adults.

Introduction: Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested.

Brief Report: Seroprevalence of Pertussis Infection in HIV-Infected Adults in the United States.

Pertussis is a resurgent infection that can cause significant morbidity among adults. CD4 T cells are necessary for its clearance, but pertussis studies in HIV-infected adults are limited to case reports. We analyzed stored serum samples from 299 HIV-infected adults to determine the seroprevalence of pertussis among this population.

Shedding of Oral Poliovirus Vaccine (OPV) by HIV-Infected and -Uninfected Mothers of OPV-Vaccinated Zimbabwean Infants.

Community circulation of oral poliovirus vaccine (OPV) likely begins with household transmission. We analyzed stool collected from Zimbabwean mothers who were infected with human immunodeficiency virus (HIV) and those who were uninfected with HIV 1 to 24 weeks after infant oral poliovirus vaccination. Overall, only 5% of the mothers had detectable OPV (16 of 304) despite high infant shedding rates.

Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.

Background: Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers.

Community circulation patterns of oral polio vaccine serotypes 1, 2, and 3 after Mexican national immunization weeks.

Background: With wild poliovirus nearing eradication, preventing circulating vaccine-derived poliovirus (cVDPV) by understanding oral polio vaccine (OPV) community circulation is increasingly important. Mexico, where OPV is given only during biannual national immunization weeks (NIWs) but where children receive inactivated polio vaccine (IPV) as part of their primary regimen, provides a natural setting to study OPV community circulation.

Methods: In total, 216 children and household contacts in Veracruz, Mexico, were enrolled, and monthly stool samples and questionnaires collected for 1 year; 2501 stool samples underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3.

The differential diagnosis of hypoglycorrhachia in adult patients.

Objectives: Hypoglycorrhachia, a low glucose level in the cerebrospinal fluid (CSF), can suggest bacterial, fungal or tuberculous meningitis. When tests for these common infectious etiologies are negative, many clinicians are unsure of which diagnoses to consider, resulting in delayed treatment. The authors analyzed the diagnoses associated with hypoglycorrhachia to determine their relative frequencies at our institution and summarized all the diagnoses associated with hypoglycorrhachia in the literature.

Real-time Polymerase Chain Reaction Analysis of Sewage Samples to Determine Oral Polio Vaccine Circulation Duration and Mutation After Mexican National Immunization Weeks.

Background: Oral polio vaccine (OPV) can mutate and cause outbreaks of paralytic poliomyelitis with prolonged replication. After poliovirus eradication, global use of inactivated polio vaccine (IPV) may be needed until all OPV stops circulating. Mexico, where children receive routine IPV but where OPV is given only during biannual national immunization weeks (NIWs), provides a natural setting to study duration of OPV circulation in a community primarily vaccinated with IPV.

Vaccine poliovirus shedding and immune response to oral polio vaccine in HIV-infected and -uninfected Zimbabwean infants.

Background: With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV.

Head and neck emergencies: bacterial meningitis, encephalitis, brain abscess, upper airway obstruction, and jugular septic thrombophlebitis.

Head and neck infectious disease emergencies can be rapidly fatal without prompt recognition and treatment. Empiric intravenous (IV) antibiotics should be initiated immediately in any patient with suspected bacterial meningitis, and IV acyclovir in any patient with suspected encephalitis. Surgical intervention is often necessary for brain abscesses, epiglottitis, and Ludwig's angina.

Adjuvants and inactivated polio vaccine: a systematic review.

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV.

Immunologic response to oral polio vaccine in human immunodeficiency virus-infected and uninfected Zimbabwean children.

Background: Poliovirus eradication is dependent on maintaining adequate community-wide levels of serologic protection. Many African countries with conditions that favor continued wild poliovirus propagation also have a high prevalence of pediatric human immunodeficiency virus (HIV) infection. Data are limited regarding the degree of serologic immunity conferred on HIV-infected children after immunization with oral polio vaccine (OPV).