Post-antiretroviral Therapy Era Research Articles

Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta-analysis.

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta-analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta-analysis was conducted with the random-effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low-income and middle-income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28-0.65, I2=99%, Cochran's Q=1027.44, P<0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17-0.52, I2=99%, Cochran's Q=1027.44, P<0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, inAsian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post-antiretroviral therapy era and from high-income countries.

Low rate of pre-exposure prophylaxis and post-exposure prophylaxis uptake and high prevalence of transmitted drug resistance among newly diagnosed primary HIV infections in Shenzhen, China: a real-world retrospective study.

Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen. This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People's Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed. Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q1-Q3: 24.0-34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only. Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

The Clinical Features and Immunological Signature of Cyclospora cayetanensis Co-Infection among People Living with HIV in Ghana.

Background: There is a paucity of information on the contemporary burden, disease patterns, and immunological profile of people living with HIV who are co-infected with C. cayetanensis in the post-antiretroviral therapy era. Methods: For this cross-sectional study, stool samples of 640 HIV-positive and 83 HIV-negative individuals in Ghana were tested for C. cayetanensis. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and immunological parameters were assessed. Results: The prevalence of C. cayetanensis was 8.75% (n = 56) in HIV-positive and 1.20% (n = 1) in HIV-negative participants (p = 0.015). Within the group of HIV-positive participants, the prevalence reached 13.6% in patients with CD4+ T cell counts below 200 cells/µl. Frequencies of the clinical manifestations of weight loss and diarrheal disease were significantly higher in patients with C. cayetanensis compared to those without co-infection (36.36% vs. 22.59%, p = 0.034 and 20.00% vs. 4.90%, p < 0.001, respectively). The expression of markers of immune activation and exhaustion of T lymphocyte sub-populations was significantly elevated in patients colonized with C. cayetanensis. Conclusions: In the modern post-combined antiretroviral therapy (cART) era, the acquisition of C. cayetanensis among PLWH in Ghana is driven largely by the immunosuppression profile characterized by high expression of markers of immune activation and immune exhaustion.

Factors Related to Advanced Stage of Cancer Presentation in Botswana.

PurposeBotswana, a country with a high prevalence of HIV, has an increasing incidence of cancer-related mortality in the post–antiretroviral therapy era. Despite universal access to free health care, the majority of Botswana patients with cancer present at advanced stages. This study was designed to explore the factors related to advanced-stage cancer presentation in Botswana.MethodsPatients attending an oncology clinic between December 2015 and January 2017 at Princess Marina Hospital in Gaborone, Botswana, completed a questionnaire on sociodemographic and clinical factors as well as cancer-related fears, attitudes, beliefs, and stigma. Odds ratios (ORs) were calculated to identify factors significantly associated with advanced stage (stage III and IV) at diagnosis.ResultsOf 214 patients, 18.7% were men and 81.3% were women. The median age at diagnosis was 46 years, with 71.9% of patients older than 40 years. The most commonly represented cancers included cervical (42.3%), breast (16%), and head and neck (15.5%). Cancer stages represented in the study group included 8.4% at stage I, 19.2% at stage II, 24.1% at stage III, 11.9% at stage IV, and 36.4% at an unknown stage. Patients who presented at advanced stages were significantly more likely to not be afraid of having cancer (OR, 3.48; P < .05), believe that their family would not care for them if they needed treatment (OR, 6.35; P = .05), and believe that they could not afford to develop cancer (OR, 2.73; P < .05). The perception that symptoms were less serious was also significantly related to advanced stage (P < .05). Patients with non–female-specific cancers were more likely to present in advanced stages (OR, 5.67; P < .05).ConclusionFuture cancer mortality reduction efforts should emphasize cancer symptom awareness and early detection through routine cancer screening, as well as increasing the acceptability of care-seeking, especially among male patients.

Rheumatic diseases in HIV-infected patients in the post-antiretroviral therapy era: a tertiary care center experience.

The aim of the study was to calculate the proportion of rheumatic diseases in HIV patients who were receiving ART and to identify association of the HIV medications with the development of rheumatologic diseases. We conducted a retrospective chart review during the period of 2010 to 2016. We identified 2996 patients as having chronic HIV infection and on ART, and we collected data regarding patient's demographic characteristics, comorbidities, CD 4 count, HIV viral load, and ART. One hundred thirteen out of 2996 HIV patients (3.8%) were found to have a rheumatic condition (mean age of 48.6years, 83% male). The most frequent musculoskeletal condition was avascular necrosis (AVN) in 39 (1.3%), and the most frequent autoimmune condition was psoriasis in 28 patients (1%). Compared with the 200 HIV patients without any diagnosis of rheumatic disease were the older patients with rheumatic conditions (mean age of 48.9 vs. 42.7years; p < 0.01), and had a longer duration of HIV infection (mean duration of 15.5 vs. 10.3years; p < 0.01). The odds of rheumatic conditions were 1.7 times higher in males (relative to females). Those who received integrase inhibitors were more likely (63.3%) to develop rheumatologic manifestations relative to those who never received integrase inhibitors (21.6%; p < 0.01). The proportion of rheumatic diseases in HIV patients appears to be comparable to the prevalence in the US population. Older age, longer duration of HIV infection, and the use of ART regimens containing integrase inhibitors, appear to increase the risk of developing a rheumatic condition.

Advance Care Planning and HIV in the Post-Antiretroviral Therapy Era: A Narrative Review (FR481B)

Advance Care Planning and HIV in the Post-Antiretroviral Therapy Era: A Narrative Review (FR481B)

Insights into human immunodeficiency virus-hepatitis B virus co-infection in India.

Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study.

Chemokine CXCL8 promotes HIV-1 replication in human monocyte-derived macrophages and primary microglia via nuclear factor-κB pathway.

BackgroundChemokine CXCL8 is an important neutrophil chemoattractant implicated in various neurodegenerative disorders. Cytokine/chemokine imbalance, with an increase in proinflammatory cytokines like interleukin-1β and tumor necrosis factor-α within the central nervous system, is a hallmark of human immunodeficiency virus (HIV)-1 infection. We previously reported that HIV-1 infection is linked to upregulation of CXCL8 in brain tissues and human astrocytes. Chemokines play crucial roles in trafficking of leukocytes and trafficking of HIV-1-infected across the blood-brain barrier play an important role in HIV-1 central nervous system disease. In the post-antiretroviral therapy era, low level of productive replication of HIV-1 in brain is a critical component of neuropathogenesis regulation. The present study investigated the effect of CXCL8 on productive infection of HIV-1 in human monocytes-derived macrophages (MDM) and primary human microglia.ResultsHuman MDM and microglia were infected with the blood or brain derived HIV-1 isolates, HIV-1ADA or HIV-1JRFL. Treatment with CXCL8 significantly upregulated HIV-1p24 levels in supernatants of both HIV-1-infected MDM as well as microglia. In addition, the formation of 2-long terminal repeat (LTR) circles, a measure of viral genome integration, was significantly higher in CXCL8-treated, HIV-1-infected MDM and microglia. Transient transfection of U937 cells with HIV-1 LTR luciferase reporter construct resulted in increased promoter activity when treated with CXCL8. Moreover, increased nuclear translocation of nuclear factor-κB was seen in HIV-1-infected MDM following CXCL8 treatment. Blocking CXCL8 receptors CXCR1 and CXCR2 abrogated the CXCL8-mediated enhanced HIV-1 replication.ConclusionOur results show that CXCL8 mediates productive infection of HIV-1 in MDM and microglia via receptors CXCR1 and CXCR2. These results demonstrate that CXCL8 exerts its downstream effects by increasing translocation of nuclear factor-κB into the nucleus, thereby promoting HIV-1 LTR activity.

Hcv Treatment Challenges in Patients Co-Infected with HIV

Infection with HCV is one of the most challenging co-morbidities emerging in HIV-infected patients in the post-antiretroviral therapy era. The co-infected population differs from the HCV mono-infected population in several aspects. HIV accelerates hepatic fibrosis progression, cirrhosis, end-stage liver disease, the development of hepatocellular carcinoma and death. Co-infected patients have a lower likelihood of achieving sustained virological response to treatment compared with mono-infected ones. A growing number of co-infected patients have a past history of nonresponse or relapse along with advanced liver disease. The simultaneous treatment of HCV and HIV may be associated with the occurrence of drug interactions, overlapping toxicities, and increased incidence and severity of side effects. This population is sorely in need of treatment. State-of-the-art management requires different strategies to achieve a cure with minimal adverse events. This review focuses on specific treatment challenges encountered in the current treatment of HCV in HIV-seropositive individuals.