Introduction Of Antiretroviral Therapy Research Articles

Nef mediates neuroimmune response, myelin impairment, and neuronal injury in EcoHIV-infected mice.

The introduction of antiretroviral therapy has markedly improved the management of HIV-associated neurocognitive disorders (HAND). However, HAND still affects nearly half of HIV-infected individuals, presenting significant challenges to their well-being. This highlights the critical need for a deeper understanding of HAND mechanisms. Among HIV viral proteins, Nef is notable for its multifaceted role in HIV pathogenesis, though its specific involvement in HAND remains unclear. To investigate this, we used a murine model infected with Nef-expressing (EcoHIV) and Nef-deficient (EcoHIVΔNef) murine HIV. Comparative analyses revealed increased neuroinflammation and reduced myelin and neuronal integrity in EcoHIV-infected brains compared with those with EcoHIVΔNef. Both viruses induced astrogliosis, with stronger GFAP activation in Nef-deficient infections. These findings suggest that Nef contributes to neuroinflammation, primarily through microglial targeting and demyelination, although other factors may regulate astrogliosis. Our results indicate that Nef may significantly contribute to neuronal injury in EcoHIV-infected mice, offering insights into Nef-induced neuropathology in HAND and guiding future research.

Abstract 4144514: Human Immunodeficiency Virus Associated Cardiomyopathy- A Rare Cause of Heart Failure With Reduced Ejection Fraction in Era of Highly Active Antiretroviral Therapy

Introduction: Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era. Case Report: A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device. Discussion: Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

HIV disease progression among heterosexually-infected individuals before the introduction of universal ART in China: A linear mixed-effects model.

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm3. From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV.

Influence of the Type of Antiretroviral Treatment on the Time to Reach High Pharmacotherapy Complexity in People Living With HIV.

The introduction of antiretroviral therapy (ARV) has significantly improved the survival of people living with HIV (PLWH), increasing the proportion of individuals over 50 years old. This aging trend poses challenges, such as the development of age-related comorbidities and a higher prevalence of polypharmacy. The pharmacotherapeutic complexity, assessed using the Medication Regimen Complexity Index (MRCI), is crucial for identifying and optimizing treatment, especially in elderly and polymedicated patients. The main objective was to assess the association between different ARV regimens and the time required to reach a high level of pharmacotherapeutic complexity in PLWH. A single-center observational analytical research study was conducted, including adult PLWH on active ARV from January 2010 to December 2021 with follow-up until December 2023. An analysis of the time to reach MRCI ≥11.25 was performed, followed by a Cox regression model to determine the influence of ARV on high MRCI. A total of 789 PLWH were included, median age of 52 years (interquartile range: 45-58). Overall, 195 patients had an MRCI value ≥11.25 with a mean time to reach it of 181.86 months (95% confidence interval [CI]: 176.24 to 187.49). Significant differences were observed in sex, advanced age, AIDS stage, presence of comorbidities, polypharmacy, and ARV-related variables. A multivariate Cox proportional hazards model showed an association between integrase inhibitor (INSTI)-containing regimens (hazard ratio [HR]: 1.83; 95% CI: 1.08 to 3.10) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (HR: 0.72; 95% CI: 0.52 to 0.98) with the time to reach high MRCI. In summary, NNRTI-based regimens were associated with a lower likelihood of developing high MRCI compared to INSTI-based regimens, which was associated with a higher likelihood. These conclusions are based on a profile of PLWH that included advanced age and a high prevalence of comorbidities and polypharmacy. Identifying high MRCI may help us implement pharmacotherapeutic optimization strategies to improve health outcomes.

HIV/AIDS in Papua New Guinea: A Comprehensive Review

This comprehensive review examines the HIV/AIDS epidemic in Papua New Guinea (PNG), a country characterized by its unique cultural and geographical context. Although the global HIV/AIDS crisis began in the early 1980s, PNG’s first case was not recorded until 1987. Since then, the epidemic has significantly impacted the nation, evolving into a critical public health challenge. This review explores the historical context, epidemiology, socioeconomic impacts, and public health responses to HIV/AIDS in PNG. The epidemiological analysis highlights the generalized nature of the epidemic in PNG, with heterosexual transmission being the predominant mode. Key populations, such as sex workers and men who have sex with men (MSM), are disproportionately affected due to social stigma, discrimination, and limited access to healthcare. Regional disparities in prevalence are also notable, with urban areas and certain provinces, particularly in the Highlands region, experiencing higher burdens of the disease. The socioeconomic impacts of HIV/AIDS in PNG are profound, straining the already limited healthcare infrastructure and exacerbating poverty, especially in rural areas. The review discusses how cultural factors, including traditional beliefs, polygamy, and the practice of bride price, contribute to the spread of HIV and hinder public health interventions. Stigma and discrimination further complicate efforts to manage the epidemic, often deterring individuals from seeking testing and treatment. Public health responses in PNG have included preventive campaigns, expanded testing and counseling services, and the introduction of Antiretroviral Therapy (ART) programs. Community-based approaches, such as peer education and support groups, have also played a crucial role in combating the epidemic. Despite these efforts, challenges remain, including geographic isolation, cultural barriers, and limited resources. The review concludes with future directions and recommendations for strengthening PNG’s healthcare infrastructure, addressing stigma and discrimination, enhancing prevention strategies, and investing in research and surveillance. These measures are essential for controlling the HIV/AIDS epidemic and improving the overall health and well-being of the population in Papua New Guinea. Keywords: HIV/AIDS, Papua New Guinea, epidemiology, public health, Antiretroviral Therapy (ART).

Prevalence and patterns of echocardiographic abnormalities among people living with HIV on anti-retroviral therapy in Kumasi, Ghana

BackgroundEchocardiography can be used to screen, confirm, and assist in the management of some cardiovascular diseases in people living with human immunodeficiency virus (HIV) (PLWH). Thus, complications from subclinical cardiovascular conditions or more apparent conditions, such as massive pericardial effusion with tamponade, can be promptly identified and managed to minimize cardiovascular morbidity and mortality associated with HIV infection. Since the introduction of antiretroviral therapy (ART) in Ghana approximately two decades ago, studies on the prevalence and patterns of echocardiographic abnormalities among PLWH on ART have been limited. This study was designed to assess the prevalence and patterns of echocardiographic abnormalities among PLWH on ART.MethodsThis was a cross-sectional study. PLWH on ART (cases) attending the HIV clinic at Komfo Anokye Teaching Hospital (KATH) and HIV-negative blood donors (controls) were consecutively recruited and enrolled in this study. The interviews were performed via a standardized questionnaire. After a clinical examination was performed, all patients underwent two-dimensional (2D) and Doppler transthoracic echocardiograms. The prevalence and patterns of echocardiographic abnormalities were characterized.ResultsThere were 117 patients in each arm of the study. There were more females than males among both the cases (92 (78.6%) and controls (80 (68.4%)); however, the sex distribution was similar between the two groups (p = 0.075). For clinical characteristics such as age, weight, height and blood pressure, there were no statistically significant differences between the cases and controls. Echocardiographic abnormalities were more frequently observed and demonstrated a statistically significant difference between cases and controls, with an overall prevalence of 35.0% among cases and 19.7% among controls (p = 0.008). The echocardiographic abnormalities that demonstrated significant differences between the cases and controls were left ventricular (LV) diastolic dysfunction (28.2% versus 8.6%; p = 0.000) and LV hypertrophy (7% versus 0.9%; p = 0.017).ConclusionNearly 1 in 3 PLWH on ART had an echocardiographic abnormality in this Ghanaian study. Echocardiograms are recommended as helpful screening modalities for diagnosing cardiac abnormalities among PLWH on ART.

Factors influencing adherence to antiretroviral therapy among young adults in Limpopo province.

South Africa is among the countries with the greatest burden of human immunodeficiency virus (HIV) in the world. The introduction of antiretroviral therapy (ART) has made HIV a manageable chronic health condition with a return to normal life expectancy. Adherence to ART is a prerequisite to realising these benefits. A qualitative study was conducted using individual semi-structured interviews to understand factors influencing adherence to ART among young adults. The study was conducted at three busy primary care clinics around Mankweng Hospital. Participants aged 18-35 years who had been on ART for more than a year were purposefully selected. Open-ended questions were used to explore factors that influence ART. Recorded interviews were transcribed verbatim and translated. The coded transcripts were thematically analysed. Eight major themes were identified to influence ART adherence among young adults: medication-related factors, healthcare system factors, attitudes of healthcare workers, economic factors, disclosure, acceptance, mobile phone reminders and family support. Adherence to ART is a major problem in our communities, and people living with HIV are still finding it challenging to optimally adhere to their ART medication because of the identified factors that influence ART adherence. Family support is a significant factor that was identified to positively influence ART as it leads to disclosure and acceptance of HIV-positive status, better emotional well-being and subsequently improved ART adherence.Contribution:This study underscores the importance of a family-oriented, patient-centred care approach in managing HIV and ART adherence.

Serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir and ritonavir-boosted atazanavir-based antiretroviral therapy: a comparative cross-sectional study.

After the introduction of antiretroviral therapy, the care given to people living with HIV has become complicated by the appearance of comorbidities as a result of HIV and HAART toxicities, in which cardiovascular disease got the most attention. So, this study aimed to assess serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir (DTG) and ritonavir-boosted atazanavir (ATV/r)-based therapy. An institutional-based comparative cross-sectional study was conducted from November 4, 2021, to January 4, 2022. An equal number of dolutegravir- and ritonavir-boosted atazanavir-treated patients (n = 86 each) were enrolled. A consecutive sampling method was used to select participants. Data were entered into Epidata version 4.6, exported to SPSS version 25.0, and analyzed using Chi-square, Student's t-test, Mann-Whitney U-test, and logistic regression. Statistical significance was set at p < 0.05. The prevalence of hyperuricemia and high-sensitivity C-reactive protein levels ≥2 mg/L were 46.5% (40/86) and 24.4% (21/86) in the DTG group, and 30.2% (26/86) and 44.2 (38/86) in the ATV/r group, respectively. When compared to ATV/r, a higher mean level of uric acid was found among DTG-based regimens (5.38 mg/dL). Duration of ART (AOR = 2, 95% CI: 1.2, 4.4) and DTG-based regimen (AOR = 1.9, 95% CI: 1.04, 3.8) were significant predictors of developing hyperuricemia. ATV/r-based regimen (AOR = 3, 95% CI: 1.5, 8.3) and high waist circumference (AOR = 2.5, 95% CI: 1, 3.5) were significantly associated with increased high-sensitivity C-reactive protein levels. It is observed that DTG-based and ATV/r-based ART are associated with hyperuricemia and increased high-sensitivity C-reactive protein levels, respectively. Therefore, it is important to consider and evaluate serum uric acid and high-sensitivity C-reactive protein levels in patients taking DTG and ATV/r-based ART, as well as among those on HAART for years and with a higher waist circumference, so as to detect and prevent early the risk of having CVD.

Neurocognitive profile in HIV subjects on INSTI-regimen- one year follow up: Is there room for optimism?

The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.

Trends in HIV/AIDS-Related Mortality and the Impact of Antiretroviral Treatment Strategies in Lu'an City: A Comprehensive Analysis.

BACKGROUND There are many factors that affect human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related deaths, and different antiretroviral therapy (ART) strategies may affect HIV/AIDS-related fatality rates. However, studies on this area are very limited. This study aimed to evaluate the factors associated with HIV/AIDS-related mortality and the impact of different ART strategies in Lu'an City, Anhui Province, China, 1999-2023. MATERIAL AND METHODS Data of HIV/AIDS cases were downloaded from the China HIV/AIDS Comprehensive Response Information Management System, and were assessed to evaluate the impact of different ART strategies on the related fatality rate using interrupted time series (ITS). RESULTS We found that age at diagnosis of 15 years, 25 years, 40 years, and 60 years, as well as receiving ART, were protective factors against death (with P below 0.05), while lower CD4 count at the last CD4 count and the year of diagnosis before 2007 and between 2007 and 2016 were risk factors (with P below 0.05). ITS analysis revealed that in the year of the introduction of free ART in 2006, the fatality rate decreased by 38.60% (P=0.015). The fatality rate trend from 2006 to 2015 was -1.1%, which was not statistically significant (P=0.434). The fatality rate trend from 2016 to 2023 was -0.33%, indicating a decreasing trend (P=0.000). CONCLUSIONS Children under 15 years old and elderly patients had a higher risk of death. The main reasons for the decrease in HIV/AIDS-related fatality rate were ART, especially the "early treatment" strategy.

Immunotherapy in HIV-associated Kaposi Sarcoma: Challenges and Prospects

Abstract: Kaposi Sarcoma [KS] stems from malignant endothelial cells targeting the cutaneous and lymphatic systems. The aetiological agent, human herpesvirus type 8, has been implicated in the induction of KS. Of the four variants of KS that exist, HIV/AIDS associated KS remains one of the leading cancers in people living with HIV in sub-Saharan Africa [SSA]. It is estimated that approximately 80% of KS cases were attributed to HIV in 2020. Although the introduction of anti-retroviral therapy [ART] alleviated the burden in 1981, its prevalence on the continent remains significant in comparison to the rest of the world. Traditional therapeutics such as chemotherapy continue to be the most common form of managing HIV-associated KS; however, the incidence of this global cancer continues to rise, predominantly in SSA. Furthermore, a significant number of HIV/AIDS-associated KS patients had been observed with normal CD4+ count and low viral load levels. This necessitates the development of other therapeutic strategies to collectively manage the continental crisis. Various strategies, such as immunomodulatory agents, monoclonal antibodies and therapeutic cytokines, are being investigated to be used as potential therapeutic strategies. One strategy highlights targeting the signalling pathways and growth factors involved in angiogenesis, which is an important characteristic of KS. The PD-1/PD-L1 immune checkpoint blockades are particularly interesting since cell cycle inhibitors have shown promising results as a potential immunotherapeutic agent. Predictive biomarkers and alternative vaccines will be discussed here while potential barriers which reduce the impact of immunotherapy are discussed throughout the review.

Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.

Despite the success of combination antiretroviral therapy (ART) for individuals living with HIV, mild forms of HIV-associated neurocognitive disorder (HAND) continue to occur. Brain microglia form the principal target for HIV infection in the brain. It remains unknown how infection of these cells leads to neuroinflammation, neuronal dysfunction, and/or death observed in HAND. Utilizing two different inducible pluripotent stem cell-derived brain organoid models (cerebral and choroid plexus [ChP] organoids) containing microglia, we investigated the pathogenic changes associated with HIV infection. Infection of microglia was associated with a sharp increase in CCL2 and CXCL10 chemokine gene expression and the activation of many type I interferon stimulated genes (MX1, ISG15, ISG20, IFI27, IFITM3 and others). Production of the proinflammatory chemokines persisted at low levels after treatment of the cell cultures with ART, consistent with the persistence of mild HAND following clinical introduction of ART. Expression of multiple members of the S100 family of inflammatory genes sharply increased following HIV infection of microglia measured by single-cell RNA-seq. However, S100 gene expression was not limited to microglia but was also detected more broadly in uninfected stromal cells, mature and immature ChP cells, neural progenitor cells and importantly in bystander neurons suggesting propagation of the inflammatory response to bystander cells. Neurotransmitter transporter expression declined in uninfected neurons, accompanied by increased expression of genes promoting cellular senescence and cell death. Together, these studies underscore how an inflammatory response generated in HIV-infected microglia is propagated to multiple uninfected bystander cells ultimately resulting in the dysfunction and death of bystander neurons.

Comparison on treatment outcomes of patients enrolled on anti-retroviral therapy at different levels of the health-care system in a high HIV/AIDS setting.

HIV/AIDS prevalence in Botswana is amongst the highest in the world and remains a significant public health problem. however, the introduction of anti-retroviral therapy (ART) lead to a significant reduction in morbidity and mortality. Decentralization of anti-retroviral therapy has improved access to treatment for people living with HIV. Treatment outcomes for patient initiated on treatment at different levels of care is unknown and this study seeks to compare treatment outcomes of patients enrolled on ART at different levels of the health care. This is a retrospective cross-sectional study that included review of data from January 2017 to December 2018. The study was conducted in 2 health districts in the country. Nine hundred and sixty (960) patient's record were included in analysis. More than half (63%) of patients were enrolled at primary care level while 37% were at tertiary level. Sixty one percent (n = 587) were female while 39% (n = 373) were males. There were no statistically significant differences in viral load suppression after 12 months of treatment between patients enrolled at tertiary level and primary care level, x2 = 0.75, p value = 0.56. Time to initiation was longer at tertiary (median = 126) compared to primary are level (median = 18), p < 0.001. We reccommend further decentralization of ART services to lower levels of the health care system to initiate PLWHIV early on treatment and improve their health outcomes and reduce transmission through treatment by prevention.

Evaluation of human herpesvirus-8 viremia and antibody positivity in patients with HIV infection with human herpesvirus-8-related diseases.

Human herpesvirus-8 (HHV-8) viremia is associated with refractory conditions in patients infected with HIV-1. Therefore, we evaluated the factors related to plasma HHV-8-DNA. Participants included patients infected with HIV-1 who visited our hospital. Plasma HHV-8-DNA levels were measured using real-time polymerase chain reaction, and anti-HHV-8 antibodies were assessed through enzyme immunoassays using multiple antigens (K8.1, ORF59, ORF65, and LANA). Factors related to plasma HHV-8-DNA were examined using Fisher's exact test or Mann-Whitney U test. The study involved 36 patients infected with HIV-1, of whom 19 were histologically diagnosed with Kaposi's sarcoma (KS), two had multicentric Castleman's disease (MCD), and 15 did not exhibit HHV-8-related disease. Before the introduction of antiretroviral therapy (ART), plasma HHV-8-DNA was detected in 44% (7/16) of patients with KS and in 9% (1/11) of patients without HHV-8-related disease. Among patients with KS, elevated plasma HHV-8-DNA levels (≥0.05 copies/µL) correlated with the presence of CDC category C diseases other than KS (p = 0.0337), anti-HHV-8 antibody negativity (p = 0.0337), anemia (p = 0.0474), and thrombocytopenia (p = 0.0146). Following ART initiation, the percentage of patients positive for plasma HHV-8-DNA decreased from 44% (7/16) to 6% (1/17), and the percentage of patients positive for anti-HHV-8 antibodies increased from 44% (7/16) to 88% (15/17). Finally, plasma HHV-8-DNA positivity and anti-HHV-8 antibody negativity were observed in two patients with MCD. Our findings suggest that insufficient production of anti-HHV-8 antibodies was associated with HHV-8 viremia, and that anti-HHV-8 antibody production was recovered with ART; thus, indicating the possibility of involvement of humoral immunity in suppressing HHV-8 viremia.

HIV-DNA decrease during treatment in primary HIV-1 infection with three different drug regimens: Italian Network of Acute HIV Infection (INACTION) clinical trial.

As the introduction of antiretroviral therapy (ART) during primary HIV-1 infection (PHI) could restrict the establishment of HIV reservoirs, we aimed to assess the effect of three different ART regimens on HIV-DNA load in people living with HIV (PLWH), who started ART in PHI. Randomized, open-label, multicentric study, including subjects in PHI (defined as an incomplete HIV-1 Western blot and detectable plasma HIV-RNA) in the Italian Network of Acute HIV Infection cohort. Participants were randomly assigned (10:10:8) to a fixed-dose combination of tenofovir alafenamide fumarate (TAF) 10 mg plus emtricitabine (FTC) 200 mg, darunavir 800 mg, and cobicistat 150 mg once daily (group A), or TAF 25 mg plus FTC 200 mg, dolutegravir 50 mg once daily (group B), or an intensified four-drug regimen (TAF 10 mg plus FTC 200 mg, dolutegravir 50 mg, darunavir 800 mg, and cobicistat 150 mg once daily) (group C). The primary endpoint was the decrease of HIV-DNA copies/106 peripheral blood mononuclear cells (PBMCs) at weeks (W) 12 and 48. Secondary endpoints were increased in CD4+ cells and in CD4+/CD8+ ratio and percentage of PLWH reaching undetectable HIV-RNA. HIV-DNA was quantified by Droplet Digital PCR (Biorad QX100) and normalized to RPP30 reference gene. This study was registered in ClinicalTrials.gov (number NCT04225325). Among 78 participants enrolled, 30 were randomized to group 1, 28 to group 2, and 20 to group 3. At baseline, median CD4+ count was 658/µL (476-790), HIV-RNA 5.37 (4.38, 6.12) log10 copies/mL, without statistical difference in their change among groups at weeks 12 and 48 (p = 0.432 and 0.234, respectively). The trial was prematurely discontinued for slow accrual and for COVID-19 pandemic-associated restrictions. In the per-protocol analysis, PLWH (n = 72) with undetectable viral load was 54.3% at W12 and 86.4% at W48. Interestingly, the CD4/CD8 ratio progressively increased over time, up to normalization in almost half of the cohort by week 48, despite a deflection in group 3; no difference was observed by the Fiebig stage (I-III vs. IV-VI). HIV-DNA decreased from 4.46 (4.08, 4.81) log10 copies/106 PBMCs to 4.22 (3.79, 4.49) at week 12, and 3.87 (3.46, 4.34) at week 48, without difference among groups. At multivariable analysis, HIV-DNA delta at W48 was associated only with the increase of CD4+ count by 100 cells/mm3 but not with the Fiebig stage, the CD4+/CD8+ ratio, and treatment arm, despite a higher decrease in group 3. Six adverse events were recorded during our study, which did not cause any withdrawal from the study. We observed a decrease in HIV-DNA from baseline to W48 in PLWH treated during PHI, associated with an increase in CD4+ count, unrelated to the treatment arm.

Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review

HIV-associated neurocognitive disorders (HAND) are the result of the activity of HIV-1 within the central nervous system (CNS). While the introduction of antiretroviral therapy (ART) has significantly reduced the occurrence of severe cases of HAND, milder cases still persist. The persistence of HAND in the modern ART era has been linked to a chronic dysregulated inflammatory profile. There is increasing evidence suggesting a potential role of Viral protein R (Vpr) in dysregulating the neuroinflammatory processes in people living with HIV (PLHIV), which may contribute to the development of HAND. Since the role of Vpr in neuroinflammatory mechanisms has not been clearly defined, we conducted a scoping review of fundamental research studies on this topic. The review aimed to assess the size and scope of available research literature on this topic and provide commentary on whether Vpr contributes to neuroinflammation, as highlighted in fundamental studies. Based on the specified selection criteria, 10 studies (6 of which were cell culture-based and 4 that included both animal and cell culture experiments) were eligible for inclusion. The main findings were that (1) Vpr can increase neuroinflammatory markers, with studies consistently reporting higher levels of TNF-α and IL-8, (2) Vpr induces (neuro)inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and Sur1-Trpm4 channels in astrocytes and the p38 and JNK-SAPK in myeloid cells, and (3) Vpr-specific protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. Therefore, Vpr should be investigated for its potential contribution to neuroinflammation in the development of HAND.

Quality of life and its determinants in people living with Human Immunodeficiency Virus infection in Kannur District, Kerala

Introduction: The prevalence of Human Immunodeficiency Virus (HIV) infection in India is on decline. Since the introduction of Anti Retroviral Therapy, the survival of HIV positives has improved a lot. HIV/acquired immunodeficiency syndrome (AIDS) is now a chronic yet manageable disease. However, social factors like stigma and discrimination still exist, affecting the quality of life (QoL) of people living with HIV (PLHIV)/AIDS. The objectives of the study were to assess the QOL among HIV-positive patients using the World Health Organization-QOL BREF (WHO-QOL BREF) questionnaire, the factors determining the QoL of HIV-positive patients, and the stigma and discrimination faced by HIV positives in the medical field. Methods: A cross-sectional study was done during the study period of 1 year. A total of 150 PLHIV from Kannur district in Kerala participated in the study. The WHO-QOL BREF, Scale and the HIV stigma scale were used to collect the data. Results: The QoL score found in the study was 15.36 ± 2.18, 2.18. The overall QoL was influenced by education, the Stigma Scale score, having a constant income or an increased income after diagnosis, and a Perceived Social Support Scale score. The study also found that 22% (33) of the participants faced stigma and discrimination from the medical field in one form or another. Conclusion: The study found that the QOL of PLHIV in the Kannur district of Kerala revealed no difference between men and women. The determinant factors for QOL were found to vary in each domain. Education was found to have a negative impact on QOL.

Virologic Nonsuppression Among Patients With HIV Newly Diagnosed With Cancer at Uganda Cancer Institute: A Cross-Sectional Study.

AIDS-related mortality declined markedly since the introduction of antiretroviral therapy (ART); however, cancer mortality in Africa was higher than its incidence in 2020. People living with HIV (PLWHIV) are at an increased risk of malignancy and death from malignancy compared with the general population. In Uganda, AIDS-defining malignancies (ADMs), including cervical cancer, Kaposi sarcoma, and non-Hodgkin lymphoma, are among the commonest malignancies. Virologic nonsuppression has been identified as an important predictor of mortality among PLWHIV diagnosed with cancer. This study aimed to determine the prevalence and to identify factors associated with virologic nonsuppression among PLWHIV newly diagnosed with cancer. This was a cross-sectional study that was carried out between December 2018 and April 2019 at the Uganda Cancer Institute. PLWHIV who had been on ART for at least 6 months and were newly diagnosed with cancer were enrolled. A total of 167 participants were enrolled. Cervical cancer was the commonest ADM (n = 45; 50.6%) of all ADMs, while esophageal and breast cancers were the commonest non-ADMs, accounting for 17.5% (n = 14) each of all non-ADMs. The prevalence of virologic nonsuppression was 15%. Having Kaposi sarcoma (odds ratio [OR], 8.15; P = .003), being poorly adherent to ART (OR, 4.1; P = .045), and being on second-line ART (OR, 5.68; P = .011) were associated with virologic nonsuppression. The prevalence of virologic nonsuppression is high among patients with HIV newly diagnosed with cancer. These findings emphasize the need for strengthening of adherence strategies, optimizing ART regimens, and prioritization of viral load testing among PLWHIV with newly diagnosed malignancy.

A scoping review of lung function in children and adolescents living with HIV in the era of antiretroviral treatment.

Human immunodeficiency virus (HIV) in children and adolescents remains an important health challenge in many countries and is commonly associated with lung disease. The introduction of antiretroviral therapy (ART) has greatly improved survival but chronic lung disease is a common ongoing challenge. We conducted a scoping review of studies that have reported lung function in school-aged children and adolescents living with HIV. A systematic literature search was performed by searching Medline, Embase, and PubMed databases, limited to articles published between 2011 and 2021 in English language. Inclusion criteria were studies involving participants living with HIV aged 5-18 years and having spirometry data. The primary outcome was lung function as measured by spirometry. Twenty-one studies were included in the review. Most study participants were living in the sub-Saharan African region. The prevalence of reduced forced expiratory volume in 1 s(FEV1 ) ranged from 25.3% to 73% across studies, reduced forced vital capacity (FVC) ranged from 10% to 42% and reduced FEV1 /FVC ranged from 3% to 26%. The mean z-score of FEV1 ranged from -2.19 to -0.73, mean zFEV1 /FVC ranged from -0.74 to 0.2, and mean FVC ranged from -1.86 to -0.63. There is a high prevalence of lung function impairment in children and adolescents living with HIV, which persists in the ART era. Further studies are needed of interventions that might improve lung function in these vulnerable populations.

Human Immunodeficiency Virus and Uveitis.

Uveitis is one of the most common ocular complications in people living with the Human immunodeficiency virus (HIV) and can be classified into HIV-induced uveitis, co-infection related uveitis, immune recovery uveitis, and drug-induced uveitis. The introduction of antiretroviral therapy has considerably changed the incidence, diagnosis, and treatment of different types of HIV-related uveitis. Furthermore, the specific immune condition of patients infected with HIV makes diagnosing HIV-related uveitis difficult. Recent studies have focused on the growing prevalence of syphilis/tuberculosis co-infection in uveitis. Simultaneously, more studies have demonstrated that HIV can directly contribute to the incidence of uveitis. However, the detailed mechanism has not been studied. Immune recovery uveitis is diagnosed by exclusion, and recent studies have addressed the role of biomarkers in its diagnosis. This review highlights recent updates on HIV-related uveitis. Furthermore, it aims to draw the attention of infectious disease physicians and ophthalmologists to the ocular health of patients infected with HIV.