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The Pan African Medical Journal 2024tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study...
INTRODUCTION
tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs).
METHODS
a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05).
RESULTS
two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109).
CONCLUSION
site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.
Topics: Humans; Nigeria; HIV Infections; Adult; Female; Antitubercular Agents; Male; Tuberculosis; Middle Aged; Coinfection; Treatment Outcome; Young Adult; Anti-HIV Agents; Isoniazid; Retrospective Studies; Tuberculosis, Pulmonary
PubMed: 38933432
DOI: 10.11604/pamj.2024.47.149.35719 -
AIDS (London, England) Jul 2024Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is...
Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.
Topics: Humans; Benzoxazines; Cyclopropanes; Female; Alkynes; Breast Neoplasms; HIV Infections; Middle Aged; Adult; Anti-HIV Agents; Survival Analysis; Aged
PubMed: 38932749
DOI: 10.1097/QAD.0000000000003912 -
Vaccines Jun 2024Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC)...
Retrospective, Observational Analysis on the Impact of SARS-CoV-2 Variant Omicron in Hospitalized Immunocompromised Patients in a German Hospital Network-The VISAGE Study.
AIMS
Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany.
METHODS
This retrospective, observational study, analyzed administrative data from inpatient cases ( = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with ( = 2037) and without IC diagnoses ( = 14,772). Secondary analyses were conducted on IC patients with ( = 2037) and without COVID-19-related SARI ( = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death.
RESULTS
In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, < 0.001), based on higher in-hospital mortality (OR = 1.4, < 0.001), increased need for ICU treatment (OR = 1.3, < 0.001) and mechanical ventilation (OR = 1.2, < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, < 0.001).
CONCLUSIONS
Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients.
PubMed: 38932363
DOI: 10.3390/vaccines12060634 -
Vaccines May 2024The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited...
The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm. We observed a negative correlation between the pre-vaccination level of CD8 T cell exhaustion and CD4 T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.
PubMed: 38932307
DOI: 10.3390/vaccines12060578 -
Viruses Jun 2024Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is... (Review)
Review
Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection.
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.
Topics: Simian Immunodeficiency Virus; Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Humans; HIV; Disease Models, Animal; Haplorhini; Lymphocyte Depletion
PubMed: 38932264
DOI: 10.3390/v16060972 -
Viruses Jun 2024The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated...
The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.
Topics: Humans; HIV-1; Pakistan; HIV Infections; Drug Resistance, Viral; Adult; Male; Female; Genetic Variation; Mutation; Phylogeny; Anti-HIV Agents; Middle Aged; Young Adult; Genotype; Adolescent
PubMed: 38932254
DOI: 10.3390/v16060962 -
Viruses May 2024Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal-oral routes, emphasizing the...
Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal-oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization's (WHO) endemicity classification aids in understanding prevalence and control strategies. This study examines 2023 South African epidemiological data on HAV cases, evaluating age distribution, incidence rates, and provincial disparities. Data from the national surveillance system and weather services were analyzed. Findings reveal distinct age-related trends, with the highest seroprevalence observed in the 5-9 age group with the most burdened areas located in the Western Cape, KwaZulu-Natal, and Gauteng provinces. Furthermore, seasonal rainfall variations correlate with increased incidence in Western Cape and KZN. The amalgamation of results suggest a potential epidemiological shift, emphasizing the need for updated immunization strategies. Noteworthy patterns, like the rise in 5-9-year-olds, may be influenced by factors such as school clustering and migration. Provincial disparities and the impact of climatic events underscore the necessity for dynamic vaccination strategies and surveillance network enhancements. This study highlights the urgency for improved understanding and response to HAV in South Africa.
Topics: Humans; South Africa; Hepatitis A; Child; Child, Preschool; Adolescent; Male; Incidence; Female; Adult; Seroepidemiologic Studies; Young Adult; Infant; Epidemiological Monitoring; Middle Aged; Prevalence; Aged; Infant, Newborn; Seasons; Age Distribution
PubMed: 38932186
DOI: 10.3390/v16060894 -
Viruses May 2024People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals...
People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants], was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/μL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece.
Topics: Humans; HIV Infections; Male; Female; Coinfection; Antiviral Agents; Adult; Greece; Middle Aged; Hepatitis C; Hepacivirus; Sustained Virologic Response; Homosexuality, Male; Hepatitis C, Chronic; Cohort Studies; Sexual and Gender Minorities
PubMed: 38932178
DOI: 10.3390/v16060885 -
Viruses May 2024The HIV-1 nucleocapsid protein (NC) is a multifunctional viral protein necessary for HIV-1 replication. Recent studies have demonstrated that reverse transcription (RT)...
The HIV-1 nucleocapsid protein (NC) is a multifunctional viral protein necessary for HIV-1 replication. Recent studies have demonstrated that reverse transcription (RT) completes in the intact viral capsid, and the timing of RT and uncoating are correlated. How the small viral core stably contains the ~10 kbp double stranded (ds) DNA product of RT, and the role of NC in this process, are not well understood. We showed previously that NC binds and saturates dsDNA in a non-specific electrostatic binding mode that triggers uniform DNA self-attraction, condensing dsDNA into a tight globule against extending forces up to 10 pN. In this study, we use optical tweezers and atomic force microscopy to characterize the role of NC's basic residues in dsDNA condensation. Basic residue mutations of NC lead to defective interaction with the dsDNA substrate, with the constant force plateau condensation observed with wild-type (WT) NC missing or diminished. These results suggest that NC's high positive charge is essential to its dsDNA condensing activity, and electrostatic interactions involving NC's basic residues are responsible in large part for the conformation, size, and stability of the dsDNA-protein complex inside the viral core. We observe DNA re-solubilization and charge reversal in the presence of excess NC, consistent with the electrostatic nature of NC-induced DNA condensation. Previous studies of HIV-1 replication in the presence of the same cationic residue mutations in NC showed significant defects in both single- and multiple-round viral infectivity. Although NC participates in many stages of viral replication, our results are consistent with the hypothesis that cationic residue mutations inhibit genomic DNA condensation, resulting in increased premature capsid uncoating and contributing to viral replication defects.
Topics: HIV-1; Reverse Transcription; DNA, Viral; gag Gene Products, Human Immunodeficiency Virus; Humans; Cations; Virus Replication; Microscopy, Atomic Force; Virion; Mutation
PubMed: 38932164
DOI: 10.3390/v16060872 -
Viruses May 2024HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be...
HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP ( 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.
Topics: Humans; Female; Male; Tanzania; Middle Aged; Risk Factors; HIV Infections; Aged; Prevalence; AIDS Dementia Complex; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Neurocognitive Disorders
PubMed: 38932112
DOI: 10.3390/v16060819