Adverse drug reactions, adherence, and virologic outcomes in adult patients on dolutegravir-based antiretroviral therapy at a tertiary hospital, southeast Nigeria.

Objective: To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy. Design: This was a retrospective chart review. Setting: A tertiary health facility-based study in Abakaliki, Nigeria. Participants: Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25. Main outcome measures: Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated. Results: The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m2, and a 2.6% increase in the prevalence of overweight and obesity. Conclusions: Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain. Funding: None declared.

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Antiviral potential of spirulina in individuals with human immunodeficiency virus or Hepatis C virus infections: A systematic review and meta-analysis.

BACKGROUND: Spirulina, a cyanobacterium or blue-green algae that contains phycocyanin, nutritional supplementation has been evaluated in patients living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) due to its antiviral properties. This supplementation may be beneficial in low resource settings when awaiting antiretroviral therapy (ART) for HIV. This review aimed to evaluate the effectiveness of Spirulina supplement in antiviral-naïve HIV- and HCV-infected patients by assessing its immunological effect (Cluster of Differentiation 4 or CD-4 T-cell count) and disease progression (viral load). METHODS: We searched PubMed, Cochrane Library, Scopus, and Web of Science from inception through January 23, 2024. Two authors independently performed the study selection, data extraction, and risk of bias assessment. We pooled data by using a random-effects model and evaluated publication bias by a funnel plot. RESULTS: We identified 5552 articles, 5509 excluded at the title and abstract stage with 44 studies making it to the full text review. Of these 6 studies met the eligibility for inclusion in the final analysis as follows: 4 randomized controlled trials (RCTs) and 2 non-RCTs. The pooled results of the Spirulina intervention found significant improvements in biomarkers of clinical outcomes, viral load (VL) and CD4 T-cell (CD4) counts, in participants of the treatment group compared to controls; the VL had an overall Cohen's d effect size decrease of -2.49 (-4.80, -0.18) and CD4 had an overall effect size increase of 4.09 (0.75, 7.43). [Cohen's d benchmark: 0.2 = small effect; 0.5 = medium effect; 0.8 = large effect]. CONCLUSIONS: Findings from this systematic review showed a potential beneficial effect of Spirulina supplementation in HIV- and HCV-infected patients by increasing CD4 counts and decreasing viral load. However, further research in larger controlled clinical trials is needed to fully investigate the effect of this nutritional supplement on clinically relevant outcomes, opportunities for intervention, optimal dose, and cost-benefit of Spirulina supplementation.

Association between HIV and acquisition of rifamycin resistance with first-line TB treatment: a systematic review and meta-analysis.

BACKGROUND: Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can be directly transmitted or arise through resistance acquisition during first-line TB treatment. Limited evidence suggests that people living with HIV (PLHIV) might have an increased risk of acquired rifamycin-resistance (ARR). METHODS: To assess HIV as a risk factor for ARR during first-line TB treatment, a systematic review and meta-analysis was conducted. ARR was defined as rifamycin-susceptibility at treatment start with rifamycin-resistance diagnosed during or at the end of treatment, or at recurrence. PubMed/MEDLINE, CINAHL, Cochrane Library, and Google Scholar databases were searched from inception to 23 May 2024 for articles in English; conference abstracts were also searched from 2004 to 2021. The Mantel-Haenszel random-effects model was used to estimate the pooled odds ratio of any association between HIV and ARR among individuals receiving first-line TB treatment. RESULTS: Ten studies that included data collected between 1990 and 2014 were identified: five from the United States, two from South Africa and one each from Uganda, India and Moldova. A total of 97,564 individuals were included across all studies, with 13,359 (13.7%) PLHIV. Overall, 312 (0.32%) acquired rifamycin-resistance, among whom 115 (36.9%) were PLHIV. The weighted odds of ARR were 4.57 (95% CI, 2.01-10.42) times higher among PLHIV compared to HIV-negative individuals receiving first-line TB treatment. CONCLUSION: The available data, suggest that PLHIV have an increased ARR risk during first-line TB treatment. Further research is needed to clarify specific risk factors, including advanced HIV disease and TB disease severity. Given the introduction of shorter, 4-month rifamycin-based regimens, there is an urgent need for additional data on ARR, particularly for PLHIV. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022327337.

Preference for daily (1HP) vs. weekly (3HP) isoniazid-rifapentine among people living with HIV in Uganda.

BACKGROUND: Both 1 month of daily (1HP) and 3 months of weekly (3HP) isoniazid-rifapentine are recommended as short-course regimens for TB prevention among people living with HIV (PLHIV). We aimed to assess acceptability and preferences for 1HP vs. 3HP among PLHIV. METHODS: In a cross-sectional survey among PLHIV at an HIV clinic in Kampala, Uganda, participants were randomly assigned to a hypothetical scenario of receiving 1HP or 3HP. Participants rated their level of perceived intention and confidence to complete treatment using a 0-10 Likert scale, and chose between 1HP and 3HP. RESULTS: Among 429 respondents (median age: 43 years, 71% female, median time on ART: 10 years), intention and confidence were rated high for both regimens. Intention to complete treatment was rated at least 7/10 by 92% (189/206 randomized to 1HP) and 93% (207/223 randomized to 3HP). Respectively 86% (178/206) and 93% (208/223) expressed high confidence to complete treatment. Overall, 81% (348/429) preferred 3HP over 1HP. CONCLUSIONS: Both 1HP and 3HP were highly acceptable regimens, with 3HP preferred by most PLHIV. Weekly, rather than daily, dosing appears preferable to shorter duration of treatment, which should inform scale-up and further development of short-course regimens for TB prevention.

CONTEXTE: L'association isoniazide-rifapentine est recommandée comme traitement de courte durée pour la prévention de la TB chez les personnes vivant avec le VIH (PVVIH), à raison d'un mois de traitement quotidien (1HP) et de 3 mois de traitement hebdomadaire (3HP). Nous avons cherché à évaluer l'acceptabilité et les préférences des PVVIH pour le traitement 1HP par rapport au traitement 3HP. MÉTHODES: Dans le cadre d'une enquête transversale menée auprès de PVVIH dans une clinique VIH de Kampala, en Ouganda, les participants ont été assignés de manière aléatoire à un scénario hypothétique de réception de 1HP ou de 3HP. Les participants ont évalué leur niveau d'intention perçue et de confiance pour terminer le traitement en utilisant une échelle de Likert de 0 à 10 et ont choisi entre 1HP et 3HP. RÉSULTATS: Parmi les 429 répondants (âge médian : 43 ans, 71% de femmes, durée médiane de la thérapie antirétrovirale : 10 ans), l'intention et la confiance ont été jugées élevées pour les deux schémas. L'intention de terminer le traitement a été évaluée à au moins 7/10 par 92% (189/206 randomisés pour 1HP) et 93% (207/223 randomisés pour 3HP). Respectivement 86% (178/206) et 93% (208/223) ont exprimé une grande confiance dans le fait de terminer le traitement. Dans l'ensemble, 81% (348/429) ont préféré la 3HP à la 1HP. CONCLUSION: Les schémas 1HP et 3HP étaient tous deux très acceptables, le schéma 3HP étant préféré par la plupart des PVVIH. L'administration hebdomadaire, plutôt que quotidienne, semble préférable à une durée de traitement plus courte, ce qui devrait inspirer l'extension et le développement de schémas thérapeutiques de courte durée pour la prévention de la TB.

Multiple sexually transmitted infections as a presenting feature of human immunodeficiency virus/AIDS.

A 45-year-old married male presented with nonhealing, painless ulcers with purulent discharge over genitals for 3 months. He had molluscum contagiosum over genitalia and forehead. A tissue smear suggested a diagnosis of donovanosis. Biopsy suggested diagnosis of molluscum contagiosum and serology was positive for human immunodeficiency virus 1 and herpes simplex 2. The patient was started on acyclovir and doxycycline. Antiretroviral therapy was initiated. The patient responded slowly over a period of 8 weeks. Immunocompromised patients having nonhealing genital ulcers must be subjected to tissue smear to pick up the diagnosis of granuloma inguinale.

Atypical presentation of molluscum contagiosum infection in a human immunodeficiency virus-positive patient.

Molluscum contagiosum (MC) is a skin infection caused by a virus of the poxvirus family. The infection is usually innocuous and inconsequential, occasionally resolving spontaneously. It is rarely associated with such severe physical and psychological morbidity. The clinical lesions are usually painless papules or nodules with central umbilication. Painful anogenital tumors exhibiting a cerebriform surface have rarely been reported. MC infection in human immunodeficiency virus (HIV)-infected patients may present with generalized papules and papulonodules, and sometimes, progression to tumorous lesions. Early detection and effective treatment of the infection in HIV patients will go a long way in preventing progression to tumors, which are known to be resistant to treatment. The tumors responded well to X-ray external beam radiotherapy.

A cross-sectional study of the factors influencing adherence to antiretroviral therapy among adults with human immunodeficiency virus infection in a tertiary care hospital in Puducherry, India.

Context: Combating human immunodeficiency virus/acquired immunodeficiency syndrome epidemic has been possible due to advances in prevention strategies and Antiretroviral therapy (ART). Optimal adherence to ART is a major factor in achieving the desired immunological, virological, and patient well-being outcomes. Several socio-demographic, patient, treatment, and health-care system-related factors influence nonadherent behavior to ART. Aims: This study was planned to assess (1) ART adherence level, (2) factors and reasons associated with nonadherence, and (3) impact of suboptimal adherence on treatment outcomes. Settings and Design: This was a cross-sectional analytical study of 300 patients in a tertiary care hospital in Puducherry, India. Methods: Random sampling was used to collect data from patient treatment cards and a predesigned structured questionnaire. The pill count method was used to calculate adherence level. Statistical Analysis Used: Nonadherence was chosen as a dependent variable and factors affecting adherence were chosen as independent variables. Test for significance was carried out by Chi-square test and Fisher's exact test. Results: Optimal adherence was seen in 68.3%. Factors significantly associated with nonadherence were lower education level, high prior CD4 count, irregular follow-up, missing doses in the past, and being late for pharmacy pill refills. Adherence was positively associated with mean increase in CD4 count over 6 months. Conclusions: In our study, the adherence rate is suboptimal which can lead to failure of ART. Nonadherence was associated with a decrease in CD4 count overtime. Most of the factors significantly affecting ART adherence were patient behavior related. These factors can be used for target intervention during reinforcement adherence counseling.

Can ferritin be a surrogate marker for CD4 cells in human immunodeficiency virus patients? A cross-sectional study of association of serum ferritin levels with immunological staging of human immunodeficiency virus patients.

Introduction: The human immunodeficiency virus (HIV)/AIDS in India came into public view in 1986 with the detection of the first case of HIV in Chennai, Tamil Nadu, and the first AIDS case in Mumbai, Maharashtra in 1987. In acute phase response, iron distribution occurs in the liver and mononuclear phagocytic system. A high prevalence of elevated serum ferritin levels is reported in HIV infection and serum ferritin levels increase with the clinical worsening of infection and with decreasing CD4 lymphocyte counts. This study is designed to find the role of acute phase reactant serum ferritin in the progression of the disease of HIV which is complicated by opportunistic infections, by finding the correlation of serum ferritin with immunological stages of HIV. Materials and Methods: This cross-sectional study was conducted on 75 patients admitted to various wards of the Department of Medicine or attending medicine outdoor or ART Centre, Maharana Bhupal Government Hospital, RNT Medical College Udaipur. Serum ferritin, total iron binding capacity, and total serum iron were analyzed in Cobas® analyzer. CD4 cells are measured using the flow cytometry technique. The results were tabulated and subjected to statistical analysis. Results and Conclusion: There was a negative correlation among serum ferritin and CD4 cells with r = -0.195 which was statistically significant (P < 0.05). As the CD4 cell count decreased incidence of serum ferritin increased. Elevation of serum ferritin levels is associated with a low count of the CD4+ in HIV-diagnosed patients. In a patient diagnosed with HIV, elevated serum ferritin indicates underlying inflammatory pathology. Serum ferritin can be used as a guide to further evaluation of underlying disease in HIV patients.

Pemphigus vulgaris in association with human immunodeficiency virus infection: A management dilemma.

The association of immunobullous disorders with human immunodeficiency virus (HIV) infection is rare. Concurrence of these two conditions poses a therapeutic challenge as both cause immune dysregulation. We report pemphigus vulgaris in association with HIV infection in a 50-year-old woman who died of sepsis after receiving high-dose corticosteroids for the treatment of pemphigus vulgaris.

Development and evaluation of a high-sensitivity RT-PCR lateral flow assay for early detection of HIV-1 infection.

Early diagnosis of HIV-1 is crucial to minimize transmission, morbidity, and mortality, particularly for neonates with developing immune systems. This study aimed to develop and evaluate a simplified, high-sensitivity assay for early HIV-1 detection before seroconversion. The assay utilizes reverse-transcription-polymerase chain reaction (RT-PCR) to amplify the HIV-1 RNA protease gene. Digoxigenin (dig)-labeled forward, and biotin-labeled universal reverse primers are used, generating digoxigenin-amplicon-biotin (DAB) products. These products are detected using a lateral flow assay (LFA) containing a conjugated pad with colloidal gold-labeled 6-histidine tag-fused maltose-binding protein-monomeric streptavidin (6HISMBP-mSA-CGC). Anti-dig monoclonal antibody (mAb) and biotinylated-BSA are immobilized in the test and control line zones, respectively. Five plasma samples with known viral load (VL) were used to simulate the efficacy of early HIV-1 detection. RNA extracted from these samples was amplified by RT-PCR using the labeled primers, and DAB products were examined on agarose gel electrophoresis and LFA. RT-PCR from diluted clinical samples yielded visible DNA bands in agarose gel electrophoresis, consistent with positive LFA results. Conversely, negative samples only displayed the control line on LFA. This assay exhibited a limit of detection (LOD) of 82.29 RNA copies/mL, comparable to other nucleic acid amplification tests (NAATs). This novel technique provides a highly sensitive assay for early HIV-1 diagnosis, even with low VL, making it suitable for resource-limited settings.

Primary extrapulmonary tuberculosis diagnosis warrants extra-precautious pulmonary tuberculosis exclusion workup.

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis (an uncommon extrapulmonary tuberculosis condition) utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction. The diagnosis chiefly relied on high-end examinations, like computed tomography scans and histopathological evaluation of post-operatively resected bowel tissue, which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition. Given the geographic locations where the patient had been (and/or treated), pivotal consideration of tuberculosis-associated endemicities in those regions, like human immunodeficiency virus (HIV) infection, might have improved the case description. The obtainment of HIV-relevant histories, like intravenous drug use and sexual practice, are good places to start. The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radio-histopathological resemblance with pulmonary Mycobacterium tuberculosis. Altogether, this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative, comprehensive, systematic, and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Inferring Population HIV Viral Load From a Single HIV Clinic's Electronic Health Record: Simulation Study With a Real-World Example.

BACKGROUND: Population viral load (VL), the most comprehensive measure of the HIV transmission potential, cannot be directly measured due to lack of complete sampling of all people with HIV. OBJECTIVE: A given HIV clinic's electronic health record (EHR), a biased sample of this population, may be used to attempt to impute this measure. METHODS: We simulated a population of 10,000 individuals with VL calibrated to surveillance data with a geometric mean of 4449 copies/mL. We sampled 3 hypothetical EHRs from (A) the source population, (B) those diagnosed, and (C) those retained in care. Our analysis imputed population VL from each EHR using sampling weights followed by Bayesian adjustment. These methods were then tested using EHR data from an HIV clinic in Delaware. RESULTS: Following weighting, the estimates moved in the direction of the population value with correspondingly wider 95% intervals as follows: clinic A: 4364 (95% interval 1963-11,132) copies/mL; clinic B: 4420 (95% interval 1913-10,199) copies/mL; and clinic C: 242 (95% interval 113-563) copies/mL. Bayesian-adjusted weighting further improved the estimate. CONCLUSIONS: These findings suggest that methodological adjustments are ineffective for estimating population VL from a single clinic's EHR without the resource-intensive elucidation of an informative prior.

Retrospective study of risk markers for developing high-grade anal intraepithelial neoplasm in men who have sex with men living with HIV. / Estudio retrospectivo que evalúa marcadores de riesgo de desarrollar lesión escamosa intraepitelial anal de alto grado en hombres que tiene sexo con hombres y viven con el virus de inmunodeficiencia humana.

High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus. This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. MATERIALS AND METHODS: To describe a population of men who have sex with men living with human immunodeficiency virus followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study was. RESULTS: Ninety-four patients were analyzed, with a mean age of 39 ± 9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DISCUSSION: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. CONCLUSION: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Prevalence of sarcopenia among people living with HIV defined by the revised European working group on sarcopenia in older people.

BACKGROUND: Sarcopenia is a progressive and systemic skeletal muscle disorder associated with an increased risk of hospitalization and adverse effects on survival. This study aims to investigate the prevalence and related risk factors of sarcopenia in people living with HIV using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. METHODS: This cross-sectional study comprising 379 patients with confirmed HIV infection evaluated the appendicular skeletal muscle mass by employing the bioelectrical impedance analysis method. Muscle strength and functional mobility were analyzed using the five-time sit-to-stand test and the timed "Up and Go" test. RESULTS: The prevalence rates of pre-sarcopenia and sarcopenia among people living with HIV were 3.4 % and 2.1 % according to the revised EWGSOP2 definition. Advanced age (Odds Ratio 1.07, p = .03), lower body mass index (Odds Ratio 0.79, p = .012) and CD4+ T-cell count below 500/µl (Odds Ratio 2.22, p = .007) were identified as significant factors associated with sarcopenia. Sarcopenia was also identified as a significant correlate of frailty (p < .001). CONCLUSION: This is the first study examining the prevalence of sarcopenia in people living with HIV according to the revised EWGSOP2 clinical algorithm. Advanced age, lower body mass index and a poor immune status are determined as promoting factors of sarcopenia. Sarcopenia significantly correlates with frailty. Standardized clinical algorithms are essential for reliable sarcopenia diagnosis in people living with HIV in order to promote intervention strategies and to prevent adverse health outcomes.

Is doxycycline post-exposure prophylaxis being utilised in Germany? Insights from an online survey among German men who have sex with men.

PURPOSE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.

Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

Diagnostic Yield of Urine Xpert MTB/RIF Ultra in Adults With Suspected Extrapulmonary Tuberculosis.

We assessed the diagnostic yield of urine GeneXpert MTB/RIF Ultra and factors associated with a positive test among adult patients suspected to have extrapulmonary tuberculosis. Urine Ultra was positive in 14% of participants with definite or probable tuberculosis. Hospitalization, disseminated tuberculosis, and human immunodeficiency virus infection were associated with a positive result.

Effects of SNPs on TNF-α and IL-10 cytokine expression in TB and HIV patients in the Capricorn district, Limpopo Province, South Africa.

Background: The impact of Tuberculosis (TB) places an immense burden on the health care system. Infection with Human Immunodeficiency Virus (HIV) is a significant risk factor in the development and progression of TB disease. Single Nucleotide Polymorphisms (SNPs) in the promoter region of Interleukin-10 (IL-10) and Tumour Necrotic Factor-Alpha (TNF-α) may play a major role in the disease mechanism and understanding these mechanisms might prove to be a useful diagnostic tool in evaluating the immune regulation and progression of the disease. Objective: This study aimed to determine the relationship between cytokine levels and gene variants of Interleukin-10 and Tumour Necrotic Factor Alpha in TB and HIV-infected participants. Methods: Cytokine levels were determined by ELISA, and SNPs were determined by MassArray®. Results: The levels of TNF-α were higher in the TB group than the HIV (p < 0.001) and TB-HIV (p = 0.011) groups, but similar to the TNF-α levels in the control group. In the HIV group, IL-10 levels were higher than those of the TB (p < 0.001) and control groups (p = 0.039), whereas there was no difference between the IL-10 levels in the HIV and the TB-HIV infection groups. The ratio was determined and there were no differences between the four infection groups. In this study, no associations were detected between the circulating plasma levels of TNF-α and IL-10 and their genotypes. Conclusion: Our data showed that the gene variants were not associated with circulating plasma levels of TNF-α and IL-10 in our study population. A pro-inflammatory environment was found in the TB and TB-HIV groups, which is suggesting of bacterial clearance, while an anti-inflammatory environment was found in the HIV group, which suggests the suppression of viral replication.