Low CD4 Count Research Articles

Magnitude of anemia and associated factors among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest Ethiopia, 2023

BackgroundAnemia is a common complication of HIV infected children and it is enabling HIV disease progression, and decreasing survival. In Ethiopia, there is limited evidence on the prevalence of anemia and its associated factors among HIV infected children particularly in the Awi Zone. Therefore, this study aimed to assess the magnitude and associated factors of anemia among HIV infected children on ART aged from 6 months to 15 year-old in ART Clinic, Awi-Zone, Ethiopia.ObjectiveTo assess the magnitude and associated factors of anemia among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest, Ethiopia, 2022.MethodsA facility based cross-sectional study design was conducted from October to December 2022. A simple random sampling method was used to select the study participants. Descriptive statistics, including frequencies and proportions was used to summarize the study variables and data had been entered in to Epi data 4.2 and exported to SPSS version 25. Bivariable logistic regression followed by multivariable logistic regression was performed. Degree of association between dependent and independent variables had been assessed using adjusted odds ratio with 95% CI at p value of ≤ 0.05.ResultFrom 346 participants in the selected sample 339 (97.9%) of them responded. Prevalence of anemia was 13.3% (n = 45) among which, majority (44.4%) of them had mild anemia, while about (42.2%,) had moderate anemia and around 13.3%, of them were severely anemic. Baseline CD4 count (AOR = 6.58, 95% CI: 2.85–15.22), WHO clinical stage III or IV (AOR = 8.42, 95% CI = 3.47, 20.45), hookworm infection (AOR = 5.06, 95% CI = 2.04, 12) and malaria infection (AOR = 4.92, 95% CI (2.19–11.02) were significantly associated with anemia among children on HAART.ConclusionThe prevalence of anemia among participants was relatively low in this study. However, a considerable proportion of participants had moderate to severe anemia. Lower CD4 count at enrolment, advanced HIV clinical stage, malaria and hookworm infection were significantly linked with anemia. Thus, it requires regular monitoring of anemia status in these patients for better clinical outcomes and quality of life improvements.

Optimizing Patient Care through Analysis of HIV-1 Genotyping: Insights into Test Ordering Strategies, Clinical Relevance, and Implications for Managing Drug Resistance

Abstract Background Antiretroviral resistance can lead to treatment failure and disease progression, especially in HIV patients. HIV-1 sequencing/genotyping tests (e.g., GenoSure) can be ordered by clinicians to detect HIV drug resistance (HIVDR). Here, we investigated our institution’s ordering practices, clinical relevance, and rates of HIVDR. Methods A total of 94 patients positive for HIV-1 between 01/2019-08/2021 were included (n=46 pre-COVID-19 prior to 03/11/2020; n=48 post-COVID-19). Patients’ charts were reviewed for demographics, laboratory results, clinical presentation, and antiviral management. Student t-test and Fisher exact test were used for statistical analyses. Results HIV-1 genotyping was ordered most by Medicine (67%), Surgery, (7%), Emergency medicine (6%), Neurology and Obstetrics & Gynecology (5% each). Only 70% of patients with GenoSure ordered and sent out had sufficient viral loads for genotyping. Among the patients with insufficient viral loads, the GenoSure test was most ordered by Medicine (68%), Surgery (9%) and Ob/Gyn (9%) departments. Our HIV patient population was predominantly male (70%) and had a mean age of 49 years (range: 25 to 90 years). Lower viral loads (1.8x105 vs. 3.4x105 copies/mL, p=0.05), CD4 counts (174 vs. 196 cells/mcL, p=0.7), CD8 counts (555 vs. 800 cells/mcL, p=0.04), and higher CD4/CD8 ratio (0.312 vs. 0.266, p=0.57) were seen in our post-COVID-19 patients. The overall prevalence of HIVDR was 20%. There was a 9% increase in HIVDR, predominantly in non-nucleotide reverse transcriptase inhibitors (NNRTI), after the COVID-19 pandemic. For example, higher resistance was documented for antiviral drugs Efavirenz (16%), Nevirapine (16%), and Rilpivirine (13%). Increased prevalence of mutations in G190A, K101, K103, and E138 positions which confer resistance to NNRTIs was seen. The GenoSure test results helped optimize antiviral therapy in 47.8% (42/88) of total cases, with an increase of 12.5% in patients from post-COVID-19 era. Infectious disease consultations led to more actionable changes (16% increase) and ordering of the updated version of the GenoSure test that includes integrase inhibitors (20% increase, p=0.005). Conclusion We have implemented stringent clinical criteria including pathologist approval and changed our electronic health record ordering system to ensure GenoSure is appropriately ordered. Diagnostic stewardship of sequencing tests needs to be implemented to ensure actionable clinical changes in the right patient population and to control testing costs. Additionally, our findings revealed increased HIVDR in our patient population post-COVID-19. Continued surveillance and collaboration with antimicrobial stewardship are critical to managing HIVDR and improving patient outcomes, particularly given the significant strain that the COVID-19 pandemic has placed on our healthcare system.

Evaluation of CMV T-cell Mediated Immunity in Children with CMV DNAemia After Allogeneic Hematopoietic Cell Transplantation

Abstract Background Cytomegalovirus (CMV) is among the most common infectious complications following allogeneic hematopoietic cell transplantation (allo-HCT). A commercially available CMV T-cell immune panel (CMV-TCIP, Viracor®), reported as percentages of CMV-specific interferon gamma releasing CD4 and CD8 cells (%CMV-CD4 or %CMV-CD8 IFN-γ), may be used to assess CMV cell-mediated immunity (CMV-CMI). However, the utility of this assay among pediatric allo-HCT recipients remains unknown. Methods A retrospective analysis among pediatric allo-HCT recipients (age ≤18 years) from 1/2020 to 11/2023 who developed CMV DNAemia and had CMV-TCIP testing was performed. Per institutional protocol, weekly quantitative plasma CMV PCR was performed until day +100. Clinically significant CMV infection (csCMVi) was defined as CMV viral load (VL) ≥500IU/ml and pre-emptive therapy (PET) was provided for csCMVi. The most frequent indications for CMV-TCIP testing were to evaluate CMV-CMI to inform the need of CMV virus-specific T-cell therapy (CMV-VST) in the setting of resistant/refractory CMV, to monitor CMV-CMI as a proxy of VST expansion post CMV-VST, or to evaluate the need of ongoing secondary antiviral prophylaxis. A %CMV-CD4 or %CMV-CD8 IFN-γ ≤0.2% was categorized as a poor response, whereas a result >0.2% was classified as an adequate response. Specimens with insufficient quality, high background, or discrepant results from %CMV-CD4 or %CMV-CD8 were classified as a discordant response. Demographics, underlying condition, HCT type, conditioning regimen, antiviral agents and use of VST, VL, and CMV-TCIP results were recorded. Descriptive and nonparametric statistics (median, interquartile range [IQR]) were used for analysis. Results Twenty-seven CMV-TCIP results from 10 unique allo-HCT recipients were analyzed. The median age at transplant was 8.5 years (IQR 2.75-14.3), predominantly for hematologic malignancy (70%). CMV donor/recipient (D/R) serostatus were D+/R+ (60%), D-/R+ (30%) and D+/R- (10%). CMV DNAemia developed post-HCT in 80% (8/10) with median onset of 4 days post-HCT (IQR 3-40) and 2 subjects had known DNAemia prior to HCT. Nine (90%) subjects were started on PET for csCMVi, whereas 1 (10%) received antiviral therapy when VL was <500IU/ml. The first CMV-TCIP was obtained at median of 112 days (IQR 42-130) post-HCT. Despite appropriate antiviral therapy, patients with a peak VL ≥500 IU/mL (obtained within 1 week before and after CMV-TCIP testing) demonstrated significantly lower absolute CD4 (median 12 vs. 198 cells/uL, p=0.02) and CD8 (median 79 vs. 443 cells/uL, p=0.04) counts and %CMV-CD4 IFN-γ (0.04% vs. 0.36%, p=0.02) compared to those with a peak VL <500 IU/mL. Conclusion Our results suggest that CMV-CMI, particularly %CMV-CD4 IFN-γ >0.2%, was observed concurrently with downward trending VL, and may serve as a proxy of VST expansion in patients receiving CMV-VSTs. Figure 1A. The distribution of peak VLs over time based on %CMV-CD4 and %CMV-CD8 IFN-γ are demonstrated in Figure 1B. CMV peak VLs were lower with TCIP testing results reported as adequate combined responses compared to those with poor combined responses. In five subjects (50%) who received CMV-VSTs as part of CMV therapy, increased %CMV-CD4 and %CMV-CD8 IFN-γ were observed post-infusion with an observed downward trend in VL.

Mpox in People With Human Immunodeficiency Virus: Predictors of Diagnosis, Outcomes, and Vaccine Effectiveness in a Multisite Cohort.

Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited. We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt. Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200-349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44-7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14-.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities. PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia.

Implementation of Antigen-Based Diagnostic Assays for Detection of Histoplasmosis and Cryptococcosis among Patients with Advanced HIV in Trinidad and Tobago: A Cross-Sectional Study.

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival.

Co-infection of cytomegalovirus and Leishmania without splenomegaly resulting in immunosuppression in an HIV-negative patient

Background: Leishmaniasis is caused by the parasite Leishmania donovani and transmitted by the bite of the sand fly vector Phlebotomus. This disease is endemic in the Bihar region of India. There are three common forms of the disease – cutaneous, mucosal and visceral leishmaniasis. The most common presentation of this disease is prolonged unexplained fever with hepatosplenomegaly. Case description: We report an unusual case of pyrexia of unknown origin (PUO) in a patient who was extensively worked up for PUO. She was found to have low CD4 counts even though serial samples were negative for HIV. Workup for PUO revealed a positive result for cytomegalovirus (CMV) IgM and polymerase chain reaction (PCR), fundoscopy suggestive of CMV retinitis and bone marrow biopsy suggestive of visceral leishmaniasis. Interestingly, there was no evidence of hepatosplenomegaly. She was diagnosed as a case of CMV infection and visceral leishmaniasis resulting in immunosuppression and was managed with parenteral ganciclovir followed by oral valganciclovir and amphotericin respectively. She had a dramatic response to the treatment and was discharged after two months of in hospital management. Conclusion: Co-infection of CMV and Leishmania in an immunocompromised patient with HIV-negative status without hepatosplenomegaly posed a diagnostic dilemma and is a rare presentation. This report shows the importance of diagnosis of this co-infectious state, which upon management with ganciclovir and amphotericin lead to resolution of symptoms and pancytopenia. Clinicians should be aware of the unusual presentation to avoid missing the diagnosis of this potentially life-threatening treatable condition.

COVID-19 Breakthrough Infections Among People With HIV: A Statewide Cohort Analysis.

This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections. This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models. Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (>500 vs <200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94). In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count.

Profile of Clinical, Radiological and Laboratory Pattern in TB-HIV Coinfection in National Infection Centre of Indonesia

Background: The study aims to map TB (Tuberculosis) – HIV (Human Immunodeficiency Virus) patients based on clinical, radiological, and laboratory patterns. Objective: This study is expected to provide previous research investigating radiologic and laboratory examinations in TB-HIV patients. Method: We conducted a cross-sectional study based on medical records of TB-HIV patients at RSPI Sulianti Saroso from January 2004 - March 2017. Samples were 240 TB-HIV patients from a population of 1014 People Living with HIV/AIDS (PLWHA). Inclusion criteria were PLWHA, aged over 18 years, diagnosed with TB with completed medical record status. Result: Characteristics of the majority of patients were in the productive age group (99.2%) with an average age of 33 years and male sex (78%). The main symptom is cough (91.7%) and cough with phlegm (59.1%). Most patients (83.37%) have not received ART (Anti-Retroviral Therapy). Pulmonary physical examination showed that most patients had Ronchi (95.8%) while others got wheezing (5%). Laboratory tests revealed an initial CD4 cell count of 71.6 cells/ml and a negative Acid-Fast Bacillus (AFB) smear (59.2%). The patient's radiology was mainly with an infiltrate (82.5%); most infiltrate was presented in apex (52.4%). Conclusion: The majority of TB-HIV coinfected patients are young males, presenting with common TB symptoms, low CD4 counts, and negative AFB smears, complicating diagnosis. Radiological findings frequently show infiltrates, particularly in the apex. These findings emphasize the importance of early diagnosis and ART initiation to improve outcomes in TB-HIV coinfected patients

Profile of Pulmonary Tuberculosis in People Living with HIV—A Cross-sectional Study

Introduction: The interface between tuberculosis (TB) and HIV is increased in countries like India where both TB and HIV infection are maximally prevalent. Worldwide, TB is the second leading infectious killer after COVID-19. Ten percent of persons infected by both TB and HIV develop TB disease annually and in one-third of them, it turns out to be fatal. HIV- tuberculosis co-infection has an atypical presentation which mostly depends on the degree of immunosuppression. Aims and Objectives: To study the socio-demographic profile, clinical manifestations, and radiological presentation with relation to the CD4 count of patients co-infected with pulmonary TB and HIV. Methodology: This is a hospital-based observational, cross-sectional study done in 100 HIV-PTB co-infected patients from Nov’2021 to Nov’2023. The study was carried out after getting Institutional ethics clearance and Informed written consent from the participants. Results: The majority (74%) were males with 75% belonging to 31–50 years of age. Fifty-eight percent had a CD4 count between 50 and 200 cells/mm 3 . Fever (90%) was the most common presenting symptom followed by cough (85%). Atypical features of TB were present in 52% of the patients. Conclusion: CBNAAT must be indicated as a primary diagnostic modality for detecting TB in PLHIV. Atypical presentations of TB on Chest X-rays are common which are attributed to low CD4 count (≤200) in the present study. Awareness regarding HIV/AIDS, safe sex practices and cough etiquette is the need of the hour.

Recurrent pulmonary nocardiosis due to Nocardia Otitidiscaviarum in a patient with isolated CD4 lymphocytopenia: a case report

BackgroundIdiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL.Case PresentationWe herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis.ConclusionsNocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL.Clinical trial numberNot applicable.

Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1

Abstract Background People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown. Methods This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S). Results A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95–1.17] vs 1.28 [IQR, 1.12–1.48]; P &amp;lt; .001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77–0.98], P &amp;lt; .001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, −0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, −0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI, .87–.94]; P &amp;lt; .001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02–1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population. Conclusions PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general population.

HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir.

Proteinuria and albuminuria among a global primary CVD prevention cohort of PWH: prevalence and associated factors.

To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors. Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial. REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results. Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values. Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.

Mpox: what sexual health physicians need to know?

Monkeypox virus (MPXV) is another zoonotic virus spilled over to the man and resulted in pandemic. World Health Organization declared it as a 'Public Health Emergency of International Concern (PHEIC) on July 22, 2022. Mpox affected over 95226 individuals among them claimed the lives of 185. Despite the fact that Mpox is generally mild and self-limited, immunocompromised people with low CD4 counts may experience severe disease course. Management of Mpox patients has three pillars. First symptomatic approach includes pain management, prophylaxis for secondary infections and when needed effective treatment of superinfections. Second, vaccines developed against smallpox can be used in preexposure or postexposure prophylaxis strategies against Mpox. Third, current antiviral options include tecovirimat, cidofovir and birincidofovir all of which have been recommended relying on experience from animal studies, clinical case reports or case series. Results of well-planned randomized control trials are not available. Occupational exposure to MPXV is especially a manageable risk for health care workers. Prevention of Mpox also requires risk communication with vulnerable population and their involvement in mitigation efforts.

Prevalence of opportunistic intestinal coccidian parasites and associated factors in HIV/AIDS patients attending anti-retroviral therapy (ART) clinic at Debre Tabor Comprehensive Specialized Hospital, Northwest Ethiopia: A cross-sectional study.

A growing number of acquired immunodeficiency syndrome (AIDS) patients suffer from opportunistic intestinal coccidian infections. Instead of human immuno deficiency virus (HIV) infection itself, opportunistic infections like intestinal coccidian parasites cause death of over 80% AIDS patients. Factors like exposed drinking water sources and poverty aid the prevalence of opportunistic intestinal coccidian parasitic infections in HIV/AIDS patients. The goal of this study was to determine the prevalence of intestinal coccidian parasites and associated factors in HIV/AIDS patients. A health facility based cross sectional study was conducted from 140 HIV/AIDS patients attending ART clinic in Debre Tabor Comprehensive Specialized Hospital, Northwest Ethiopia from September to December 2023. The sociodemographic characteristics were collected through face-to-face interviews. Stool samples were processed with Modified Acid Fast staining technique. Statistical Package for Social Sciences software version 20 was used to analyze the data. Logistic regression was used to assess factors associated with dependent variable and p < 0.05 was considered significantly associated. The total prevalence of opportunistic intestinal coccidian parasites (OICPs) in HIV/AIDS patients was 16.4% (23/140). Drinking surface water [p = 0.015, COR = 3.4] compared to tape water, drinking alcohol [p = 0.001, COR = 18] compared to not drinking alcohol, diarrhea [p = 0.005, COR = 1] compared to non-diarrheic, drug dropout [p = 0.01, COR = 11] compared to regular drug intake and low CD4 count [p = 0.042, COR = 9] compared to CD4 > 500/µL showed significant association with increased prevalence of OICPs in HIV/AIDS patients. OICPs are still the common causes of morbidity and mortality in HIV/AIDS patients. Surface water consumption, alcoholism, interruption of treatment drugs, diarrhea, and reduced CD4+ T-cells significantly contribute to acquisition and prevalence of OICPs in HIV/AIDS patients. Routine screening of OICPs with sensitive diagnostic techniques in HIV/AIDS patients regardless of symptoms is crucial and has to be practiced in health settings.

Survival Following Diagnosis of HIV-Associated Kaposi Sarcoma Among Adults in East Africa in the "Treat-All" Era.

Despite widespread access to antiretroviral therapy (ART) in the "Treat All" era, HIV-associated Kaposi sarcoma (KS) remains among the most common malignancies in sub-Saharan Africa. Survival after KS diagnosis has historically been poor in Africa, but knowledge whether survival has changed at the population level in the contemporary era has been limited by lack of community-representative surveillance and monitoring systems. We identified all adult persons living with HIV (PLWH) with a new diagnosis of KS made between 2016 and 2019 during outpatient or inpatient care at prototypical primary care-providing medical facilities in Kenya and Uganda using rapid case ascertainment. Participants were subsequently followed for vital status, including community tracking for those who became lost to follow-up. Among 411 participants with newly diagnosed KS, 71% were men, median age was 34 (IQR: 30 to 41) years, and 91% had ACTG T1 tumor extent. Over a median follow-up of 7.8 (IQR: 2.4 to 17.9) months, cumulative incidence of death (95% CI) at months 6, 12 and 18 were 34% (30% to 39%), 41% (36% to 46%) and 45% (40% to 51%), respectively. Having the highest number of anatomic sites (11 to 16) harboring KS lesions (hazard ratio 2.2 (95% CI: 1.3-3.8) compared to 1 to 3 sites) and presence of oral KS lesions (hazard ratio 2.2 (95% CI: 1.4-3.3)) were independently associated with higher mortality. Lower hemoglobin and CD4 count as well as higher plasma HIV RNA were also associated with higher mortality. Among PLWH with newly diagnosed KS in East Africa in the "Treat All" era, survival was poor and related to mucocutaneous extent of KS. The findings emphasize the need for better control of KS in Africa, including novel approaches for earlier detection, better linkage to oncologic care, and more potent therapy.

People living with HIV presenting with hemiparesis: what are the possible causes?

People living with HIV (PLWH) are commonly associated with opportunistic infections, particularly with low CD4 count, less than 200 cells/μL. Neurological manifestation can be occurred 70% in PLWH and the most symptoms is hemiparesis, seizure, headache, behavioural changes, decrease of consciousness, and cognitive impairment but depends on the localization of the brain lesions. We present a case of 53-year-old man with initial presentation of right hemiparesis and was on highly active antiretroviral therapy (HAART). With laboratory and CT-scan result, the patient diagnosed with stroke ischemic and occurred at the same time with toxoplasma encephalitis (TE) as an opportunistic infection. In PLWH, many possible causes involve central nervous system-caused hemiparesis. The initial differential diagnosis should be considered to prevent delayed treatment and potential of severe complications.

Heterogeneity in immune cell composition is associated with Mycobacterium tuberculosis replication at the granuloma level.

The control of bacterial growth is key to the prevention and treatment of tuberculosis (TB). Granulomas represent independent foci of the host immune response that present heterogeneous capacity for control of bacterial growth. At the whole tissue level, B cells and CD4 or CD8 T cells have an established role in immune protection against TB. Immune cells interact within each granuloma response, but the impact of granuloma immune composition on bacterial replication remains unknown. Here we investigate the associations between immune cell composition, including B cell, CD4, and CD8 T cells, and the state of replicating Mycobacterium tuberculosis (Mtb) within the granuloma. A measure of ribosomal RNA synthesis, the RS ratio®, represents a proxy measure of Mtb replication at the whole tissue level. We adapted the RS ratio through use of in situ hybridization, to identify replicating and non-replicating Mtb within each designated granuloma. We applied a regression model to characterize the associations between immune cell populations and the state of Mtb replication within each respective granuloma. In the evaluation of nearly 200 granulomas, we identified heterogeneity in both immune cell composition and proportion of replicating bacteria. We found clear evidence of directional associations between immune cell composition and replicating Mtb. Controlling for vaccination status and endpoint post-infection, granulomas with lower CD4 or higher CD8 cell counts are associated with a higher percent of replicating Mtb. Conversely, changes in B cell proportions were associated with little change in Mtb replication. This study establishes heterogeneity across granulomas, demonstrating that certain immune cell types are differentially associated with control of Mtb replication. These data suggest that evaluation at the granuloma level may be imperative to identifying correlates of immune protection.

Immunological and virological response to fostemsavir in routine US clinical care: An OPERA cohort study.

Fostemsavir is a novel attachment inhibitor used with other antiretrovirals in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. Real-world immunological and virological responses were assessed in individuals starting fostemsavir in the OPERA cohort. Among adults with HIV-1 starting fostemsavir between 2 July 2020 and 1 September 2022, 6-month and 12-month changes in CD4 T-cell count and CD4%, and maintenance/achievement of viral load (VL) <50 copies/mL were described and stratified by baseline VL (suppressed: <50 copies/mL; viraemic: ≥50 copies/mL) and CD4 count (high: ≥350 cells/μL; low: <350 cells/μL). Of 182 individuals starting fostemsavir, 64% were viraemic (34% low CD4, 30% high CD4) and 36% were suppressed (16% low CD4, 20% high CD4). The suppressed/low CD4 group had the largest median increases in CD4 count (6-month: 30 cells/μL [interquartile range {IQR} 9-66], 12-month: 66 cells/μL [IQR 17-125]), and CD4% (6-month: 1.0% [IQR -0.3-2.8], 12-month: 1.9% [IQR 1.3-3.9]). Regardless of baseline VL, those with a high baseline CD4 count experienced a greater variability in immunological response than those with low CD4 counts (12-month standard deviation range 172-231 cells/μL vs. 69-90 cells/μL). VL <50 copies/mL was maintained in most suppressed individuals; nearly half of the viraemic/high CD4 group and a third of the viraemic/low CD4 group achieved a VL <50 copies/mL at either timepoint. After 6 or 12 months of fostemsavir use, virological response was low in viraemic individuals, although most suppressed individuals did maintain suppression. While immunological response varied across individuals, virologically suppressed HTE individuals with low CD4 counts may benefit from immunological improvements with fostemsavir.

Concomitant Listeria monocytogenes and Streptococcus equinus brain abscess in an immunocompetent individual: a case report

BackgroundListeria monocytogenes brain abscess is a rare phenomenon that is common in immunocompromised patients. Streptococcus equinus brain abscess has never been reported in the literature to our knowledge. In this case report, we describe a case of brain abscess secondary to Listeria monocytogenes and Streptococcus equinus in an immunocompetent patient with transient low CD4 count.Case presentationA 27-year-old white, male patient, previously healthy, nonalcoholic, and occasional smoker, presented to the emergency department for confusion and headache. The patient was found to have a left parietal abscess, which was drained and the fluid was sent for culture. Culture grew Listeria monocytogenes and Streptococcus equinus. The patient was treated with intravenous ampicillin followed by oral amoxicillin for a total of 6 weeks. The CD4 count was low initially. However, after the resolution of the infection, the CD4 count came back within normal range. Another brain magnetic resonance imaging was done that showed a significantly decreased hyperintensity within the left parietal subcortical white matter at the site of surgery with significantly decreased enhancement and almost total resolution of the previous abscess.ConclusionTransient low CD4 count is a rare phenomenon that exposes patients to unusual and atypical infections. Since low CD4 count is transient, patients treated promptly recover from their illness. Our patient developed a Listeria monocytogenes and Streptococcus equinus brain abscess, which is considered rare and has not been previously described in the literature to our knowledge.