Search Results (28)

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive impairment (NCI) remains a concern despite combination antiretroviral therapy (cART), with cognitive problems often persisting even after viral suppression. The mechanisms underlying neurocognitive deterioration in people living with HIV (PLWH) and the role of plasma biomarkers remain unclear. This study aims to evaluate neurocognitive trajectories and biomarker changes in a real-world cohort of newly diagnosed PLWH initiating cART in Greece. Methods: This prospective, single-center study assessed neuropsychological performance and plasma biomarkers in treatment-naïve PLWH at baseline and 18 months after cART initiation. HIV-associated neurocognitive disorder (HAND) was classified using the Frascati criteria, and plasma biomarkers of inflammation and monocyte activation were measured. Correlations between biomarkers and cognitive performance were analyzed. Results: A total of 39 treatment-naïve PLWH were enrolled in this study. At baseline, 45.7% of participants met criteria for HAND, predominantly, asymptomatic neurocognitive impairment (ANI). Over 18 months, neurocognitive function improved, particularly in speed of information processing, executive function, and visuospatial ability, while verbal fluency, fine motor dexterity, and attention/working memory remained unchanged. Biomarkers of inflammation and monocyte activation decreased following cART, except for neopterin, which increased (10.6 vs. 13 ng/mL, p = 0.002), and plasma NFL (7.5 vs. 7.2 pg/mL, p = 0.54), which remained stable. A negative correlation between monocyte activation markers and cognitive performance was observed only at follow-up, suggesting that systemic inflammation may mask these associations in untreated PLWH. Conclusions: Early cART initiation supports neurocognitive recovery and reduces immune activation in PLWH. The observed correlation between cognitive performance and monocyte activation markers after viral suppression highlights the potential utility of plasma biomarkers in predicting cognitive impairment. Full article

Infants born to HIV-positive mothers remain at significant risk of HIV acquisition despite maternal adherence to antiretroviral therapy, cesarean delivery, and formula feeding. Our previous study reported that initiating early antiretroviral treatment at three days post-SIV infection resulted in approximately eighty percent of pediatric virologic remission. In this study, we investigated treatment outcomes in postnatally SHIV-exposed infant macaques when early intervention was delayed by two days, as well as the mechanisms underlying virologic control. The results showed that, although initiating treatment at five days post-exposure effectively suppressed viral replication, only one of the three infant macaques achieved a sustained state of virologic remission following analytical treatment interruption. Notably, this virus-controlled infant lacked detectable virus-specific immunity, including neutralizing antibodies, cytotoxic T cell responses, and antibody-dependent cellular cytotoxicity. These findings highlight the critical importance of early treatment initiation as a key determinant of virologic control in HIV-exposed, infected infants. This study provides valuable insights for guiding early pediatric HIV intervention strategies in clinical settings. Full article

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, the World Health Organisation (WHO) reported that about 1.5 million new cases of HBV occur, with approximately 820 thousand mortalities yearly. Conversely, the lower percentage of HBV (30%) cases that receive a diagnosis is a setback in achieving the WHO 2030 target for zero HBV globally. This has necessitated a public health concern to repurpose antiretroviral (ARV) drugs for the treatment of HBV diseases. This review provides an introductory background, including the pros and cons of repurposing antiretrovirals (ARVs) for HBV treatment. We examine the similarities in replication mechanisms between HIV and HBV. We further investigate some clinical studies and trials of co-infected and mono-infected patients with HIV–HBV. The topical keywords including repurposing ARV drugs, repurposing antiretroviral therapy, Hepatitis B drugs, HBV therapy, title, and abstracts are searched in PubMed, Web of Science, and Google Scholar. The advanced search includes the search period 2014–2024, full text, clinical trials, randomized control trials, and review. The search results filtered from 361 to 51 relevant articles. The investigations revealed that HIV and HBV replicate via a common route known as ‘reverse transcription’. Clinical trial results indicate that an early initiation of ARVs, particularly with tenofovir disoproxil fumarate (TDF) as part of a regimen, significantly reduced the HBV viral load in co-infected patients. In mono-infected HBV, timely and correct precise medication is essential for HBV viral load reduction. Therefore, genetic profiling is pivotal for successful ARV drug repurposing in HBV treatment. Pharmacogenetics enables the prediction of the right dosages, specific individual responses, and reactions. This study uniquely explores the intersection of pharmacogenetics and drug repurposing for optimized HBV therapy. Additional in vivo, clinical trials, and in silico research are important for validation of the potency, optimum dosage, and safety of repurposed antiretrovirals in HBV therapy. Furthermore, a prioritization of research collaborations comprising of regulators and funders to foster clinically adopting and incorporating repurposed ARVs for HBV therapy is recommended. Full article

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs). Full article

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection. Full article

CD4 count recovery is the main goal for an HIV patient who initiated ART. Early ART initiation in HIV patients can help restore immune function more effectively, even when they have reached an advanced stage. Some patients may respond positively to ART and attain CD4 count recovery. Meanwhile, other patients failing to recover their CD4 count due to non-adherence, treatment resistance and virological failure might lead to HIV-related complications and death. The purpose of this study was to find the determinants of death in patients who failed to recover their CD4 count after initiating antiretroviral therapy. The data used in this study was obtained from KwaZulu-Natal, South Africa, where 2528 HIV-infected patients with a baseline CD4 count of <200 cells/mm³ were initiated on ART. We used a Fine–Gray sub-distribution hazard and cumulative incidence function to estimate potential confounding factors of death, where CD4 count recovery was a competing event for failure due to death. Patients who had no tuberculosis were 1.33 times at risk of dying before attaining CD4 count recovery [aSHR 1.33; 95% CI (0.96–1.85)] compared to those who had tuberculosis. Rural patients had a higher risk of not recovering and leading to death [aSHR 1.97; 95% CI (1.57–2.47)] than those from urban areas. The patient’s tuberculosis status, viral load, regimen, baseline CD4 count, and location were significant contributors to death before CD4 count recovery. Intervention programs targeting HIV testing in rural areas for early ART initiation and promoting treatment adherence are recommended. Full article

Background: The battle against HIV has led to the development of antiretroviral therapy (ART), including BIKTARVY^®, which combines three potent agents. However, concerns about gastrointestinal side effects during the early phases of treatment have emerged, potentially impacting patient adherence and outcomes. Materials and Methods: This retrospective cohort study, conducted over four years in Romania, examined 222 patients initiated on BIKTARVY^® therapy. Data were collected from electronic medical records, and stringent inclusion and exclusion criteria were applied to ensure data accuracy and relevance. Statistical analysis was performed to assess age-related patterns in gastrointestinal symptoms and their relation with significant weight loss. Results: This study revealed significant differences in the prevalence of gastrointestinal symptoms between age groups, with older patients experiencing more symptoms. Notably, diarrhea did not exhibit a statistically significant age-related difference. Furthermore, weight loss exceeding 5 kg was more common in older patients. Of the patients who continued BIKTARVY^® therapy, 84.9% showed an increase in CD4 cell counts, and most expressed satisfaction with treatment. Conclusion: Understanding age-related patterns and gastrointestinal side effects of BIKTARVY^® is crucial for optimizing HIV patient care. Future research should aim to corroborate and expand upon these findings, potentially leading to improved therapeutic approaches in the ongoing fight against HIV. Full article

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010–2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010–2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015–2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 <200 cells/mmᶟ with AIDS-defining conditions (HR = 2.75, 95%CI:1.52–4.97, p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01–3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF. Full article

HIV-1 latency is a major barrier to curing infections with antiretroviral therapy and, consequently, to eliminating the disease globally. The establishment, maintenance, and potential clearance of latent infection are complex dynamic processes and can be best described with the help of mathematical models followed by experimental validation. Here, we review the use of viral dynamics models for HIV-1, with a focus on applications to the latent reservoir. Such models have been used to explain the multi-phasic decay of viral load during antiretroviral therapy, the early seeding of the latent reservoir during acute infection and the limited inflow during treatment, the dynamics of viral blips, and the phenomenon of post-treatment control. Finally, we discuss that mathematical models have been used to predict the efficacy of potential HIV-1 cure strategies, such as latency-reversing agents, early treatment initiation, or gene therapies, and to provide guidance for designing trials of these novel interventions. Full article

Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan–Meier estimator. Antiretroviral drug transmitted resistance was assessed for a sub-group of non-VLS infants. In total, 61% of infants reached VLS, and 50% had a rebound. Cumulative probability of VLS was 36%, 51%, and 69% at 6, 12 and 24 months of treatment, respectively. The median duration of VLS was 7.4 months (IQR 12.6) and the cumulative probability of rebound at 6 months was 30%. Two infants had resistance biomarkers to drugs included in their treatment regimen. Our findings point to a low rate of VLS and high rate of viral rebound. More frequent viral response monitoring is advisable to identify infants with rebound and offer timely adherence support. It is urgent to tailor the psychosocial support model of care to this specific age group and offer differentiated service delivery to mother–baby pairs. Full article

Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015–2018, measured HIV antibody, ID-NAT, and recency of infection <195 days (Sedia LAg) at enrollment and initiated early ART. A small cohort of HIV elite controllers was followed without treatment. HIV reservoir measurements included ultrasensitive plasma RNA, cell-associated HIV RNA, and total DNA. Enrollment of 18 Fiebig I–III and 45 Fiebig IV–VI HIV clade C subjects occurred a median of 18 days after index blood donation. ART was administered successfully and compliance with follow-up visits was excellent. There were only minimal differences in HIV reservoir between ART initiation in Fiebig stages I–III vs. IV–VI, but ART noncompliance increased HIV reservoir. In 11 untreated HIV elite controllers, HIV reservoir levels were similar to or higher than those seen in our early treated cohort. National blood services can identify acute HIV cohorts for subsequent HIV cure research studies. Among HIV clade C-infected donors, HIV reservoir differed little by Fiebig stage at treatment initiation, but was smaller than in chronically treated HIV and those with ART noncompliance. Full article

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients’ clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (T_SCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted T_SCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells. Full article

South Africa has the largest number of people living with HIV worldwide. South Africa has implemented five population-based HIV prevalence surveys since 2002 aimed at understanding the dynamics and the trends of the epidemic. This paper presents key findings from the fifth HIV prevalence, incidence, and behaviour survey conducted in 2017 following policy, programme, and epidemic change since the prior survey was conducted in 2012. A cross-sectional population-based household survey collected behavioural and biomedical data on all members of the eligible households. A total of 39,132 respondents from 11,776 households were eligible to participate, of whom 93.6% agreed to be interviewed, and 61.1% provided blood specimens. The provided blood specimens were used to determine HIV status, HIV incidence, viral load, exposure to antiretroviral treatment, and HIV drug resistance. Overall HIV incidence among persons aged 2 years and above was 0.48% which translates to an estimated 231,000 new infections in 2017. HIV prevalence was 14.0% translating to 7.9 million people living with HIV. Antiretroviral (ARV) exposure was 62.3%, with the lowest exposure among those aged 15 to 24 years (39.9%) with 10% lower ARV coverage among males compared to females. Viral suppression among those on treatment was high (87.3%), whilst HIV population viral load suppression was much lower (62.3%). In terms of risk behaviours, 13.6% of youth reported having had an early sexual debut (first sex before the age of 15 years), with more males reporting having done so (19.5%) than females (7.6%). Age-disparate relationships, defined as having a sexual partner 5+ years different from oneself,) among adolescents were more common among females (35.8%) than males (1.5%). Self-reported multiple sexual partnerships (MSPs), defined as having more than one sexual partner in the previous 12 months, were more commonly reported by males (25.5%) than females (9.0%). Condom use at last sexual encounter was highest among males than females. Three quarters (75.2%) of people reported they had ever been tested for HIV, with more females (79.3%) having had done so than males (70.9%). Two-thirds of respondents (66.8%) self-reported having tested for HIV in the past 12 months. Finally, 61.6% of males in the survey self-reported as having been circumcised, with circumcision being more common among youth aged 15–24 years (70.2%), Black Africans (68.9%), and those living in both rural informal (tribal) areas (65%) and urban areas (61.9%). Slightly more (51.2%) male circumcisions were reported to have occurred in a medical setting than in traditional settings (44.8%), with more young males aged 15–24 (62.6%) and men aged 25–49 (51.5%) reporting to have done so compared to most men aged 50 and older (57.1%) who reported that they had undergone circumcision in a traditional setting. The results of this survey show that strides have been made in controlling the HIV epidemic, especially in the reduction of HIV incidence, HIV testing, and treatment. Although condom use at last sex act remains unchanged, there continue to be some challenges with the lack of significant behaviour change as people, especially youth, continue to engage in risky behaviour and delay treatment initiation. Therefore, there is a need to develop or scale up targeted intervention programmes to increase HIV testing further and put more people living with HIV on treatment as well as prevent risky behaviours that put young people at risk of HIV infection. Full article

Introduction: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed to assess whether seroreversion or no seroconversion occurs using samples collected during an early treatment study in South Africa. Methods: We tested 10 longitudinal samples collected over three years from 70 blood donors who initiated ART after detection of acute or early HIV infection during donation screening on fourth- and fifth-generation HIV antibody and RNA assays, and three point of care (POC) rapid tests. Donors were allocated to three treatment groups: (1) very early, (2) early, and (3) later. Longitudinal samples were grouped into time bins post-treatment initiation. Results: On all three high-throughput HIV antibody assays, no clear pattern of declining signal intensity was observed over time after ART initiation in any of the treatment initiation groups and 100% detection was obtained. The Abbott Determine POC assay showed 100% detection at all time points with no seroreversion. However, the Abbott ABON HIV1 and OraSure OraQuick POC assays showed lower proportions of detection in all time bins in the very early treated group, ranging from 50.0% (95% CI: 26.8–73.2%) to 83.1% (95% CI: 64.2–93.0%), and moderate detection rates in the early and later-treated groups. Conclusion: While our findings are generally reassuring for HIV detection when high-throughput serological screening assays are used, POC assays may have lower sensitivity for detection of HIV infection after early treatment. Findings are relevant for blood safety and other settings where POC assays are used. Full article

Management of cryptococcal infections among patients suffering from acquired immunodeficiency syndrome (AIDS) represents a medical challenge. This retrospective study aims to describe the disease management and outcomes among 24 AIDS patients who suffered from Cryptococcus neoformans meningitis. The parameters evaluated from our patients’ database records include epidemiological data, clinical manifestations, biochemical and microbiological analysis of patients’ cerebrospinal fluid (CSF), treatment profiles, and disease outcomes. All patients included in the study had a lymphocyte count of less than 200 CD4/mm³. Of the 24 patients included in this study, five had been diagnosed with HIV infection since childhood, after receiving HIV-infected blood transfusions. The most prominent symptom was fatigue in 62.5% of patients, followed by nausea/vomiting and headache. Seven patients had liver cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, while Kaposi sarcoma and cerebral toxoplasmosis were found in two patients. Six out of 24 patients died due to bacterial sepsis and acute respiratory distress syndrome (ARDS). High intracranial pressure was the strongest predictive factor for mortality (OR = 2.9), followed by ARDS (OR = 1.8), seizures at disease onset (OR = 1.4), and diabetes mellitus (OR = 1.2). Interestingly, patients younger than 40 years old had a significantly lower survival rate than that of the older patients. Before developing Cryptococcal meningitis, all patients had low adherence to the early ART treatment scheme and skipped the follow-up visits. All patients received a combination of amphotericin B and flucytosine as induction therapy, adding fluconazole for maintenance. Simultaneously, AIDS HAART was initiated at diagnosis of the cryptococcal infection. A combined regimen of antifungals and highly active antiretroviral therapy showed improved patient recovery with minor side effects. Full article