Initiation Of Highly Active Antiretroviral Therapy Research Articles

Effects of highly active antiretroviral therapy initiation on epigenomic DNA methylation in persons living with HIV

Introduction: Highly active antiretroviral therapy (HAART) helps improve some measures of accelerated epigenetic aging in persons living with HIV (PLWH), but its overall impact on the epigenome is not fully understood.Methods: In this study, we analyzed the DNA methylation profiles of PLWH (n = 187) shortly before and approximately 2–3 years after they started HAART, as well as matched seronegative (SN) controls (n = 187), taken at two time intervals. Our aim was to identify specific CpGs and biologic pathways associated with HIV infection and initiation of HAART. Additionally, we attempted to identify epigenetic changes associated with HAART initiation that were independent of HIV-associated changes, using matched HIV seronegative (SN) controls (matched on age, hepatitis C status, and interval between visits) to identify CpGs that did not differ between PLWH and SN pre-HAART but were significantly associated with HAART initiation while being unrelated to HIV viral load. Epigenome-wide association studies (EWAS) on >850,000 CpG sites were performed using pre- and post-HAART samples from PLWH. The results were then annotated using the Genomic Regions Enrichment of Annotations Tool (GREAT).Results: When only pre- and post-HAART visits in PLWH were compared, gene ontologies related to immune function and diseases related to immune function were significant, though with less significance for PLWH with detectable HIV viral loads (>50 copies/mL) at the post-HAART visit. To specifically elucidate the effects of HAART separately from HIV-induced methylation changes, we performed EWAS of HAART while also controlling for HIV viral load, and found gene ontologies associated with transplant rejection, transplant-related diseases, and other immunologic signatures. Additionally, we performed a more focused analysis that examined CpGs reaching genome-wide significance (p < 1 × 10−7) from the viral load-controlled EWAS that did not differ between all PLWH and matched SN controls pre-HAART. These CpGs were found to be near genes that play a role in retroviral drug metabolism, diffuse large B cell lymphoma proliferation, and gastric cancer metastasis.Discussion: Overall, this study provides insight into potential biological functions associated with DNA methylation changes induced by HAART initiation in persons living with HIV.

Decreased but persistent epigenetic age acceleration is associated with changes in T-cell subsets after initiation of highly active antiretroviral therapy in persons living with HIV

IntroductionPersons living with HIV (PLWH) experience the early onset of age-related illnesses, even in the setting of successful human immunodeficiency virus (HIV) suppression with highly active antiretroviral therapy (HAART). HIV infection is associated with accelerated epigenetic aging as measured using DNA methylation (DNAm)-based estimates of biological age and of telomere length (TL).MethodsDNAm levels (Infinium MethylationEPIC BeadChip) from peripheral blood mononuclear cells from 200 PLWH and 199 HIV-seronegative (SN) participants matched on chronologic age, hepatitis C virus, and time intervals were used to calculate epigenetic age acceleration, expressed as age-adjusted acceleration residuals from 4 epigenetic clocks [Horvath’s pan-tissue age acceleration residual (AAR), extrinsic epigenetic age acceleration (EEAA), phenotypic epigenetic age acceleration (PEAA), and grim epigenetic age acceleration (GEAA)] plus age-adjusted DNAm-based TL (aaDNAmTL). Epigenetic age acceleration was compared for PLWH and SN participants at two visits: up to 1.5 years prior and 2–3 years after HAART (or equivalent visits). Flow cytometry was performed in PLWH and SN participants at both visits to evaluate T-cell subsets.ResultsEpigenetic age acceleration in PLWH decreased after the initiation of HAART but remained greater post-HAART than that in age-matched SN participants, with differences in medians of 6.6, 9.1, and 7.7 years for AAR, EEAA, and PEAA, respectively, and 0.39 units of aaDNAmTL shortening (all p < 0.001). Cumulative HIV viral load after HAART initiation was associated with some epigenetic acceleration (EEAA, PEAA, and aaDNAmTL), but even PLWH with undetectable HIV post-HAART showed persistent epigenetic age acceleration compared to SN participants (p < 0.001). AAR, EEAA, and aaDNAmTL showed significant associations with total, naïve, and senescent CD8 T-cell counts; the total CD4 T-cell counts were associated with AAR, EEAA, and PEAA (p = 0.04 to <0.001). In an epigenome-wide analysis using weighted gene co-methylation network analyses, 11 modules demonstrated significant DNAm differences pre- to post-HAART initiation. Of these, nine were previously identified as significantly different from pre- to post-HIV infection but in the opposite direction.DiscussionIn this large longitudinal study, we demonstrated that, although the magnitude of the difference decreases with HAART is associated with the cumulative viral load, PLWH are persistently epigenetically older than age-matched SN participants even after the successful initiation of HAART, and these changes are associated with changes in T-cell subsets.

Detectable Virological Load and Associated Factors among People Living with HIV on Antiretroviral Treatment: A Retrospective Study.

The complete and prolonged suppression of viral load is the primary objective of HAART in people living with HIV. Some people may experience therapeutic failure, while others may achieve virological suppression but are unable to maintain it, developing persistent or single detection of low-level viremia. This study aims to evaluate the determinants of a detectable viral load among patients on HAART to identify and address them promptly. In this retrospective study, all patients referring to the Infectious Disease Operative Unit of the Vito Fazzi Hospital in Lecce, Puglia, older than 18 years, receiving HAART for at least 12 months as of 30 June 2022, were included. For each patient, demographic characteristics such as age, sex, educational level, stable relationship, cohabitation, employment status, and information relating to habits and lifestyles such as physical activity, use of drugs, and substances or supplements for sport, abuse of alcohol, and smoking were collected. Degree of comorbidity was quantified according to the Charlson Comorbidity Index, and the presence of obesity and the COVID-19 infection was also considered. Univariable and multivariable logistic regression models were used to assess the association between patients' characteristics and the outcome. In the multivariable logistic regression model, the odds were lower for the duration of therapy (OR: 0.96; p = 0.0397), prescriber's perception of adherence to therapy (OR: 0.50; p < 0.0001), and Nadir CD4+ T-cell count (OR: 0.85; p = 0.0329), and higher for the presence of AIDS (OR: 1.89; p = 0.0423) and COVID-19 (OR: 2.31; p = 0.0182). Our findings support the early initiation of HAART to achieve virological suppression. Additionally, measures to improve adherence to therapy should be adopted to ensure better outcomes for patients.

Investigating the Role of Anti-TPO Antibodies in HIV-Associated Thrombocytopenia before and after Initiation of HAART: A Case-Control Longitudinal Study.

This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p < 0.001) and elevated the median platelet counts from 131,000 to 199,000 (p < 0.001). No significant difference in median platelet counts was found post-HAART among the anti-TPO subgroups (p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750-199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia.

Effect of immunological non-response on incidence of Non-AIDS events in people living with HIV: A retrospective multicenter cohort study in Taiwan.

People living with HIV (PLWH) are susceptible to non-AIDS-related events, particularly those with immunological nonresponses (INRs) to highly active antiretroviral therapy (HAART). This study assessed the association of INRs with incident non-AIDS-related events among PLWH. This multicenter retrospective cohort study enrolled PLWH who had newly diagnosed stage 3 HIV and received HAART between January 1, 2008, and December 31, 2019. The patients were divided into two groups according to their immunological responses on the 360th day after HAART initiation: INR and non-INR groups. Cox regression and sensitivity analyses were conducted to estimate the effects of INRs on overall and individual categories of non-AIDS-related events (malignancies, vascular diseases, metabolic disorders, renal diseases, and psychiatric disorders). Patient observation started on the 360th day after HAART initiation and continued until February 28, 2022, death, or an outcome of interest, whichever occurred first. Among the 289 included patients, 44 had INRs. Most of the included patients were aged 26-45 years (69.55%) and were men who have sex with men (89.97%). Many patients received HIV diagnoses between 2009 and 2012 (38.54%). INRs (vs. non-INRs) were associated with composite non-AIDS-related events (adjusted hazard ratio [aHR]=1.80; 95% confidence interval [CI]: 1.19-2.73) and metabolic disorders (aHR=1.75; 95% CI: 1.14-2.68). Sensitivity analyses revealed consistent results for each Cox regression model for both composite non-AIDS-related events and metabolic diseases. Clinicians should be vigilant and implement early intervention and rigorous monitoring for non-AIDS-related events in PLWH with INRs to HAART.

Immunohematological Outcome Among Adult HIV Patients Taking Highly Active Antiretroviral Therapy for at Least Six Months in Yabelo Hospital, Borana, Ethiopia.

Immunohematological abnormalities among human immunodeficiency virus-infected patients are common abnormalities associated with severe depletion of the immune system, covering a stage of acute syndrome to an advanced disease. The greatest impact was observed in the low- and middle-income countries. However, in Ethiopia, little attention has been paid, and only limited published information exists regarding immunohematological abnormalities among individuals receiving highly active antiretroviral treatment. This study aimed to assess changes in immunological and hematological parameters in HIV-infected patients receiving HAART for at least six months at the antiretroviral therapy clinic of Yabelo Hospital, Borena, Ethiopia. A cross-sectional study was conducted from February to July 2021 using convenient sampling to recruit 333 participants. Sociodemographic data and clinical characteristics were collected using a pretested questionnaire. Baseline data were extracted from medical records and after six month immunohematological measurements were performed on blood samples collected during the study period. Data analysis was performed using SPSS version 25. Descriptive analysis was performed, and the results are presented as numbers and percentages or means ± SD. A paired t-test was used to compare the mean values of the immunohematological parameters before and after six of taking HAART. Statistical significance was set at P < 0.05. The prevalence of anemia, leucopenia, neutropenia, lymphopenia and thrombocytopenia were 47.4%, 73.3%, 58.3%, 76.9% and 3.3% before initiation of HAART and 23.1%, 36.4%, 23.4%, 35.7% and 2.4% after initiation of HAART, respectively; Compared to baseline, there was also a significant decrease in the rate of Immunosuppression (CD4 < 350) from 62.2% at base line to 20.7% after HAART initiation. Immunohematological profile of the patients improved after the initiation of HAART. The observation of large proportion of immunosuppressed individuals at baseline warrants advocating for HIV testing in the pastoralist community so that infected patients could benefit from early initiation of HAART.

Long-term prognosis and overall mortality in patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

HIV Retinopathy and Immune Reconstitution Uveitis on CMV Retinitis: A Case Report

Aim: In HIV patients with CD4+count&lt;50cells/µL, after initiating HAART, close ophthalmological monitoring is mandatory, in order to watch for the development of IRU.&#x0D; Case Presentation: A 39-year-old patient with unknown medical history consulted for blurred vision and myodesopsia. The examination found bilateral microangiopathy with temporal retinal ischemia in the right eye.&#x0D; The patient was tested positive for HIV-1 with a CD4count of 43 cells/mm3. The diagnosis of HIV-microangiopathy was made, he received a prophylactic retinal argon-laser and was put on HAART.&#x0D; Following the HAART, he presented decreased VA in the right eye, with in examination, a slight inflammation of the AC, moderate hyalitis, and a diffuse and confluent temporal retinal necrosis.&#x0D; The diagnosis of IRU associated with CMV-retinitis was presumed.&#x0D; Discussion: The HAART increases the number of CD4-T-cells and restores immune responses against a wide variety of pathogens which reduces the incidence of opportunistic infections. However, in some patients, a dysregulated immune response after initiation of HAART leads to the immune reconstitution inflammatory disease, characterized by the paradoxical aggravation of a treated opportunistic infection or the revealing of a previously untreated subclinical infection in HIV-positive patients. The ocular manifestation of IRIS is called immune reconstitution uveitis (IRU).&#x0D; IRU usually develops in patients with inactive CMV retinitis, but it can rarely occur in eyes with active CMV retinitis and occurs within the first few weeks of starting HAART.&#x0D; Conclusion: The initiation of HAART requires regular general and ophthalmological monitoring in order to recognize early IRU which is often associated with active CMV retinitis.

Excess mortality and associated factors among people living with HIV initiating highly active antiretroviral therapy in Luzhou, China 2006–2020

BackgroundTo estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006–2020, and assess associated factors.MethodsPLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006–2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates.ResultsThe median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1–65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4–2.4) in 2006–2011 to 0.8 deaths/100 person-years (95%CI:0.7–0.9) in 2016–2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3–6.8) to 1.7 deaths/100 person-years (95%CI:1.5–1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2–2.1) than females. PLHIV with CD4 counts ≥ 500 cells/μL had the eHR of 0.3 (95%CI:0.2–0.5) in comparison to those with CD4 counts < 200 cells/μL. PLHIV with WHO clinical stages III/IV had greater excess mortality with the eHR of 1.4 (95%CI:1.1–1.8). PLHIV with time from diagnosis to HAART initiation ≤ 3 months had the eHR of 0.7 (95%CI:0.5–0.9) compared to those with time ≥ 12 months. PLHIV with initial HAART regimens unchanged and viral suppression had the eHR of 1.9 (95%CI:1.4–2.6) and 0.1 (95%CI:0.0–0.1), respectively.ConclusionsThe excess mortality and SMR among PLHIV initiating HAART in Luzhou, China decreased substantially from 2006 to 2020, but the mortality rate among PLHIV was still higher than general population. PLHIV who were male, with baseline CD4 counts less than 200 cells/μL, WHO clinical stages III/IV, time from diagnosis to HAART initiation ≥ 12 months, initial HAART regimens unchanged, and virological failure had a greater risk of excess deaths. Early and efficient HAART would be significant in reducing excess mortality among PLHIV.

2311. Long-term prognosis and risk factors for overall mortality in patients with progressive multifocal leukoencephalopathy

Abstract Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period. Methods We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first. Results The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality. Conclusion With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis. Disclosures All Authors: No reported disclosures.

2064. Incidence and Risk Factors for Microscopic Hematuria in a US Military HIV Cohort

Abstract Background Microscopic hematuria (MH) is a common finding on screening urinalyses in persons living with HIV (PLWH); however, a study in the pre-HAART era revealed that a complete urologic evaluation was generally non-diagnostic in young males with a benign history and normal renal function. Recent studies have shown a decreased incidence of hematuria in PLWH in the HAART era. We performed a nested case-control study in the prospectively enrolled US Military HIV Natural History Study (NHS) to evaluate characteristics of PLWH with and without MH. Methods We evaluated male participants diagnosed with HIV and enrolled in the NHS Jan 2007 to Dec 2019. MH cases were defined as having at least one urinalysis with ≥5 RBCs/hpf. We used descriptive statistics to compare cases and controls with respect to demographics, comorbidities, and laboratory findings to determine risk factors for MH. Cox regression models evaluated for independent associations with the development of MH since HIV diagnosis. Results Of 829 included participants, 142 (17.1%) had MH, of whom 87 (61.3%) had only one MH event. Cases had a shorter mean duration of study follow-up but more analyzable urinalyses per participant. There were no significant differences between cases and controls in demographics, CD4 count nadir, time from HIV diagnosis to HAART initiation, or inclusion of tenofovir disoproxil fumarate (TDF) in initial regimen. On univariate analysis, more cases had a history of urinary tract infection (UTI) or a hypertension diagnosis through the time of incident MH compared to controls, but were less likely to have proteinuria or pyuria at the time of MH. Cox regression models revealed that a history of UTI increased the hazard for MH (HR 2.07, p &amp;lt; 0.05). In contrast, the presence of proteinuria (HR 0.42, p&amp;lt; 0.01) and TDF use (HR 0.56, p&amp;lt; 0.05) decreased the hazard for MH compared to controls. Conclusion A history of UTI, though not concurrent pyuria, was associated with an increased hazard for MH. The use of TDF in the initial HAART regimen and the presence of proteinuria were protective against hematuria. Future studies are needed to clarify these findings; however, they provide reassurance that in a young, otherwise healthy cohort, MH is typically self-limited and unrelated to intrinsic renal pathology, comorbidity, or HIV-related factor. Disclosures All Authors: No reported disclosures.

Survival and Predictors of Mortality among Adults Initiating Highly Active Antiretroviral Therapy in Ethiopia: A Retrospective Cohort Study (2007-2019).

Studies have shown high early mortality after initiation of highly active antiretroviral therapy (HAART). We examined change in three-year survival and predictors of mortality of patients initiating HAART in Ethiopia since 2007 to 2019. A retrospective cohort study was conducted in 47 health facilities (HFs) using records of 11,013 adult patients initiating HAART from 2007 to 2019. Study subjects were stratified as four different cohorts based on their calendar year of HAART initiation: 2007-2010, 2011-2013, 2014-2016, and 2017-2019. HFs were selected using probability proportional to size of patients. Survival rate and predictors of mortality were estimated by the calendar year using the Kaplan-Meier and Cox proportional hazard, respectively. We generated a pooled estimate of survival rate and predicators of mortality. Data from 1881, 3868, 3004, and 2260 patients were retrieved from each of the cohorts. Overall mortality for all cohorts at all times was 10.3%. A gradual decline of mortality was observed in the first three years of follow-up since 2007-2016 which were 21.37%, 10.03%, and 4.34% among patients who initiated HAART in 2007, 2011, and 2014 respectively. A mortality jump of 9.25% was observed among patents initiating HAART in 2017, which coincided with political instability happened in the country. Of the 21,638 person-years of follow-up among 11,013 adults, mortality was 5.23/100 person-years, while disaggregated by the cohorts, it was 14.77, 5.06, 2.12, and 4.17 per 100 person-years, respectively. Among all the cohorts, patients with CD4 count of ≤200 cells/mm3, unsuppressed viral load, poor adherence, and drug resistance in all cohorts, respectively, have overall 2.0 (95%CI = 1.35 - 2.69), 4.66 (95%CI = 2.53 - 6.72), 6.78 (95%CI = 3.4 - 10.3), and 10.02 (95%CI = 6.91 - 13.82) times of mortality risk than those without. Patients with bedridden for cohort initiating HAART during 2007 and 2011 were 2.0 (95%CI = 1.35 - 2.69) times of mortality risk than those without. Patients initiating HAART from 2007 to 2016 have continuously improved their survival during three-year cohort follow-up in Ethiopia. The significant decline of survival among those who initiate HAART as of 2017 calls for program intervention. Low CD4 counts, unsuppressed viral load, poor adherence, and drug resistance could be used as predictors for increased mortality to monitor the quality of HAART and improve clinical management of HIV/AIDS patients.

S3033 HIV-AIDS: A Rare Cause of Cholestatic Cholangiopathy

Introduction: HIV/AIDS has been shown to affect hepatic parenchyma and biliary tree leading to inflammation and biliary strictures. With the advent of highly active antiretroviral therapy (HAART), it is rarely encountered, except in cases of resistance or medication non-compliance. Case Description/Methods: A 48-year-old man with history of HIV and poor compliance with HAART presented with abdominal pain, nausea and diarrhea. Physical exam showed scleral icterus and mild abdominal tenderness, with labs showing a T.bili. 16.9, AST 212, ALT 133, and ALP 3885. MRCP revealed intrahepatic biliary ductal dilatation of both lobes of liver and mild dilatation of the proximal extrahepatic CBD (9 mm) without cholelithiasis, biliary sludge or ductal stone suggesting nonspecific cholestasis. ERCP was performed which revealed papillary stenosis and moderately enlarged CBD (12 mm). Irregularities were noted in bilateral intrahepatic branches but not in ducts. A pancreatic and biliary sphincterotomy was performed. With minimal decrease in T.bili. and ALP, repeat MRCP was performed 3 months later showing persistent intrahepatic biliary ductal dilatation with normal CBD. Repeat ERCP showed patent prior sphincterotomy and the biliary tree was swept with nothing found. Further workup revealed a CD4 count of 17 and serology positive for cryptosporidium antigen. A diagnosis of HIV-cholangiopathy was made and the patient was restarted on HAART and nitazoxanide with gradual decline in T.bili and ALP. (Figure) Discussion: HIV/AIDS-cholangiopathy is a rarely encountered biliary syndrome, usually manifesting in severely immunosuppressed AIDS patients. Several opportunistic pathogens have been implicated in its pathogenesis with Cryptosporidium parvum being the most commonly associated pathogen. C. parvum predominantly affecting the biliary tract leading to apoptotic cell death of the cholangiocytes. Biliary involvement has been described in four cholangiographic patterns – papillary stenosis, extrahepatic strictures, intra and extrahepatic sclerosing lesions, and acalculous cholecystitis. Diagnosis can be established usually by MRCP or ERCP which shows papillary stenosis with intrahepatic ductal dilatation. Alternating multifocal intrahepatic strictures can also be seen giving a beaded appearance. The cornerstone of management involves the management of opportunistic infections with the initiation of HAART. The prognosis is usually poor due to advanced stages of immunosuppression and multiple opportunistic infections.Figure 1.: CT Abdomen pelvis showing intrahepatic biliary ductal dilation.

Performance of Creatinine- and Cystatin C-Based Equations for Glomerular Filtration Rate Estimation in HIV-1-Infected Individuals Receiving Dolutegravir + Tenofovir Disoproxil Fumarate + Lamivudine as Initial Antiretroviral Therapy: A Retrospective Observational Study.

Dolutegravir (DTG) may inhibit organic cation transporter-2 in renal tubules and elevate serum creatinine levels without true renal function deterioration. There are scarce data on the glomerular filtration rate (GFR) equations in Chinese HIV patients with DTG/TDF/3 TC. This retrospective study was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values among Chinese adult HIV patients with initial highly active antiretroviral therapy (HAART) with DTG/TDF/3 TC for 48 weeks. Retrospective analysis of Chinese adult HIV patients who received initial HAART with DTG/TDF/3 TC between January 2016 and May 2021. We compared the changes in creatinine-based and cystatin C-based estimated GFR before and 48 weeks after HAART to determine the optimal tool for renal function estimation. Ninety-five patients [91.58% men; median age, 34 years (interquartile range, 29-44 years)] were enrolled. The median baseline CD4+ cell count was 185 cells/µL [interquartile range, 53-303 cells/µL] and the median baseline viral load was 148,000 copies/mL [interquartile range, 26,800-596,000 copies/mL]. The estimated GFR at 4, 12, and 24 weeks was significantly different than at baseline (P < 0.05) using all 4 equations. Only the GFR estimated using the CKD-EPIcreat and CKD-EPIcys equations was significantly different at 48 weeks of treatment (P < 0.05). The modification of diet in renal disease-based decline of GFR incidence at 4, 12, 24, and 48 weeks of treatment (21.5%, 24.21%, 33.68% and 38.95%, respectively) was higher than that calculated using the other 3 GFR equations. The modification of diet in renal disease equation may not be optimal for Chinese HIV-1-infected adults receiving DTG + TDF + 3 TC as the initial antiviral therapy. Clinicians must carefully choose the GFR equation for patients with HIV/hepatitis B virus coinfection.

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 μg/L and elevated iron status was defined using ferritin > 150 μg/L among females and > 200 μg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 μg/L, while ID was defined using ferritin < 70 μg/L in the presence of inflammation and < 15 μg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR)= 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5kg/m2 , hazard ratio (HR)= 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

34244 Acquired epidermodysplasia verruciformis: A retrospective review of cases

Epidermodysplasia verruciformis is a rare genodermatosis characterized by an unusual susceptibility to the beta genus of the human papillomavirus and early development of skin cancers. Acquired epidermodysplasia verruciformis (AEDV) is a distinct rare disorder with similar clinical and histopathologic manifestation, strongly associated with immunosuppression. Clinical course, therapeutic management, and potential for skin cancer development in AEDV is largely unknown. We report 7 patients with AEDV diagnosed between January 1992 and November 2019. Four patients were males (57.1%), with median age of diagnosis of 29 years, range 9-67 years. All patients had underlying immunodeficiency; 5 with acquired immunodeficiencies (HIV/AIDS, heart transplant, kidney transplant, pancreas transplant, systemic lupus erythematosus and Crohn’s disease) and 2 with congenital immunodeficiencies (isolated CD4 lymphopenia and immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia). For patients with acquired immunodeficiencies, the median interval between the onset of immunosuppression and the presentation of AEDV lesions was 5 years, range 3-7 years. Patients were followed for a median of 5.5 years, range 1-10 years. Only 1 patient (14.2%) progressed to develop squamous cell carcinoma of the left forearm. Topical imiquimod (3/7), topical tretinoin (3/7), cryotherapy (2/7), intralesional candida injection (2/7), and topical podophyllotoxin (1/7) were attempted for treatment of AEDV. Partial resolution of AEDV lesions was observed with intralesional candida injection (2/2) and topical retinoid (1/3). Initiation of HAART yielded complete resolution in one patient with HIV/AIDS. In conclusion, we report a series of AEDV with emphasis on therapeutic management, clinical course, and long-term follow up of this rare disorder.

Magnitude and predictors of first-line antiretroviral therapy regimen change among HIV infected adults: A retrospective cross sectional study

BackgroundRegimen change remains a significant challenge towards the achievement of human immunodeficiency virus (HIV) treatment success. In developing countries where limited treatment options are available, strategies are required to ensure the sustainability and durability of the starting regimens. Nevertheless, information regarding the rate and predictors of regimen change is limited in these settings. ObjectiveThis study was undertaken to determine the prevalence and predictors of changes in ART regimens among patients initiating highly active antiretroviral therapy (HAART) at XX. Materials and methodsAn institutional based retrospective cross-sectional study was conducted among adult naïve HIV patients who had initiated HAART at XX between 2010. Data were extracted by reviewing their medical charts using a pretested structured check-list. The Kaplan–Meier survival analyses were used to describe the probability of ARV regimen changes while Cox proportional hazard regression models were employed to identify the predictors of ARV regimen modifications. Data were analyzed using SPSS version 21 software, and statistical significant was deemed at p < 0.05. ResultsA total of 770 patients were enrolled in this study of these 165 (21.43%) had their ART regimen modified at least once. Drug toxicity was the main reason for regimen change followed by TB comorbidity, and treatment failure. Positive baseline TB symptoms (aHR = 1.63, p = 0.037), and Zidovudine based regimen (aHR = 1.76, p = 0.011) as compared to Stavudine based regimen were at higher risk of ART modification. Conversely, urban residence, baseline World Health organization (WHO) stage 2 as compared to WHO stage 1, baseline CD4 count ≥301 as compared to CD4 count ≤200 were at lower risk of ART modification. ConclusionThe rate of initial HAART regimen change was found to be high. Thus, less toxic and better tolerated HIV treatment options should be available and used more frequently. Moreover, early detection and initiation of ART by the government is highly demanded to maximize the benefit and reduce risk of ART modifications.

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Immuno-virological status and its associated factors among HIV-positive patients receiving highly active antiretroviral therapy at delgi primary hospital, northwest Ethiopia, 2020/2021: A cross-sectional study

BackgroundHighly active antiretroviral therapy (HAART) improves clinical outcomes by suppressing viral replication and allowing immune reconstitution. It also reduces HIV-related complications including morbidity, mortality, and extended hospitalizations for HIV-positive individuals. Regular assessment for antiretroviral treatment response is fundamentally important to address the factors associated with the poor clinical outcome including immunologic failures among HIV-positive patients on HAART. Therefore, this study aimed to investigate the immuno-virological status and describe its determinants among HIV-positive patients receiving HAART at Delgi primary hospital, Northwest Ethiopia. MethodsA hospital-based cross-sectional study was conducted at Delgi primary hospital from October 25th through June 19th 2021 among a total of 442 study participants. A systematic random sampling technique was employed to enrol participants in the study. Socio-demographic and clinically related data were collected using a semi-structured questionnaire. About 3–5 ml of venous blood was collected aseptically for CD4+ T cell count and viral load test. SPSS version 20 software was used for statistical analysis. Bivariate and multivariate logistic regression analyses were conducted to determine the factors associated with immuno-virologic status among HIV-positive patients on HAART. The odds ratio with 95% CI was computed to determine the strength of association. Then, a p-value < 0.05 was considered a statistically significant association. For this study, the results were presented by using frequency summary tables, and texts. ResultsAmong the total study participants, 283 (64%) were males and the mean age of the study participants was 37 ± 11.5. The overall immunological and virological failure among highly active antiretroviral therapy (HAART) receiving participants was found to be 9.5% (42/442, 95%CI:3.23–15.09) and 12.2% (54/442, 95% CI: 2.81–23.04) respectively. In the multivariate analysis, study participants with age ≥50 years old [AOR = 1.97, p = 0.01, 95%CI (0.02–4.03)], participants having current viral load count greater ≥1000 copies/ml [AOR = 3.97, p = 0.03, 95%CI (1.09–5.01)] and having TB-co-infection [AOR = 2.51, p = 0.05, 95%CI (1.02–7.51)] were statistically associated with increased risk of immunological failure. Similarly, TB-coinfected participants were 1.88 (95%CI = 0.89–10.02) times at greater risk for virological failure. ConclusionIn this study, the magnitude of immuno-virological failure is alarming. This may be shown the need for integrated and substantial commitment to enhancing patient antiretroviral treatment adherence in the study area. Also, regular assessment for antiretroviral treatment response is fundamentally important to address the determinants associated with virological and immunologic failures among HIV-positive patients taking HAART. Furthermore, early initiation of HAART may be imperative to achieve favourable virological suppression and immunological reconstitution.

Treatment Outcome of MDR/RR TB in a Resource-Constrained Setup: A Four-Year Retrospective Analysis.

IntroductionThe emergence of drug resistance in TB treatment is a major public health threat. However, there are limited studies which are directed towards identifying factors that explain the gap in achieving treatment targets.Objective: This study aimed to assess the treatment outcome and its associated factors among patients with MDR/RR-TB in Dilchora Hospital Treatment Initiation Center from January 2014 to December 2018.Method: A retrospective cross-sectional study was conducted on patients with MDR/RR TB who initiated treatment between January 2014 and December 2018. Data were extracted from patient medical charts using a structured questionnaire. SPSS version 26 was used for analysis. Reports are presented using percentages and frequency. Independently associated factors for unfavorable outcome were identified using binary logistic regression model. Adjusted and crude odds ratio with 95% CI was used. P-value less than 0.05 was used to declare statistical significance.Result: A total of 146 patients were included in this study. The overall prevalence of unfavorable outcomes in this study for those with known outcomes was 8.6%. People living with HIV had a 6.47 times (95% CI: 1.14–36.68) increased odds of death as compared to those who are HIV negative. For every 1kg/m2 increment in BMI, there was a 35.3% (AOR = 0.647; CI: 0.44–0.95) reduction in the odds of death as compared to those who had a 1kg/m2 lower BMI. Each additional month without culture conversion also increased the odds of death 2.24 times (95%CI: 1.08–4.66).Conclusion & Recommendation: The findings of our study showed an appreciably low poor treatment outcome for this outpatient program. HIV screening and early initiation of HAART, early identification and treatment of those who are underweight and a critical follow-up to the time of sputum culture conversion could help in further improving the outcomes.