Introduction Of Antiretroviral Therapy Research Articles

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.

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.

Multimodality Imaging in HIV-Associated Cardiovascular Complications: A Comprehensive Review.

Human immunodeficiency virus (HIV) infection is a leading cause of mortality and morbidity worldwide. The introduction of antiretroviral therapy (ART) has significantly reduced the risk of developing acquired immune deficiency syndrome and increased life expectancy, approaching that of the general population. However, people living with HIV have a substantially increased risk of cardiovascular diseases despite long-term viral suppression using ART. HIV-associated cardiovascular complications encompass a broad spectrum of diseases that involve the myocardium, pericardium, coronary arteries, valves, and systemic and pulmonary vasculature. Traditional risk stratification tools do not accurately predict cardiovascular risk in this population. Multimodality imaging plays an essential role in the evaluation of various HIV-related cardiovascular complications. Here, we emphasize the role of multimodality imaging in establishing the diagnosis and aetiopathogenesis of various cardiovascular manifestations related to chronic HIV disease. This review also provides a critical appraisal of contemporary data and illustrative cases.

Mathematical Model for Coinfection of HIV/AIDS and Kaposi’s Sarcoma with Treatment

HIV destroys T-cells in order to target the body's defence mechanism. Without treatment HIV infection advances in stages causing destruction and reduction in T-cells thus, rendering the body incapable of fighting other infections such as respiratory infections, sexually transmitted diseases and some cancers. Kaposi’s sarcoma is the cancer that allows a tumour to grow in an HIV patient and its presence in a patient is an indication that HIV has fully developed into AIDS in the patient. Research has indicated that AIDS-associated Kaposi Sarcoma was on the rise in sub-Saharan Africa until the introduction of Antiretroviral Therapy (ART). The Kenyan community has struggled in the past decade to combat the spread of HIV/AIDS and successes have been recorded in many areas. However, Kaposi Sarcoma, an opportunistic infection, has continued to rise steadily through the years. In this study, a simple model for the coinfection of HIV/AIDS and KS is developed and studied. The model solution is explored for positivity and boundedness while the DFE point is determined for stability where it was verified that the infection-free equilibrium <I>E</I>₀ is locally asymptotically stable when <img width="40" height="10" src="http://article.sciencepublishinggroup.com/journal/247/2471233/image001.png" />. The NGM is used to derive the basic reproduction number of the model. By providing treatment to the HIV and the co-infected population immune system is strengthened and thus progression rate to AIDS is reduced.

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.

Clinicoepidemiological study of adverse cutaneous drug reactions among immunocompromised children at a tertiary care hospital.

Highly active antiretroviral therapy (HAART) is used to treat human immunodeficiency virus type 1 (HIV-1). Introduction of antiretroviral therapy (ART) has reduced the HIV/AIDS associated morbidity and mortality significantly. But 25% of all patients discontinue treatment because of adverse drug reactions (ADRs). Adverse cutaneous drug reactions (ACDR) are very common with ART regimens, which may range from mild pruritus, maculopapular rash to serious Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). ACDRs comprise 10%-30% of all reported ADRs. To assess the different types of cutaneous adverse drug reactions in immunocompromised children of less than 18years. This is a retrospective record-based study, conducted at department of Dermatology, Venereology and Leprosy, Government Medical College (GMC)/Government General Hospital (GGH), Suryapet, Telangana, India. Data was collected from the records available at ART centre, from November 2018 to October 2021 GGH, Suryapet. All the HIV infected children ≤18 years who were on ART, were included in this study. Patients of more than 18 years and on other medications were excluded. Demographic data, socio economic status, vaccination status, height, weight, complete blood analysis, complete urine analysis, erythrocyte sedimentation rate, liver and renal function tests and CD4 counts were recorded before initiation of ART. A total of 330 children of less than 18 years were initiated for ART, at ART centre, Government General Hospital, Suraypet. Out of 330 children, 27.8% (92) children developed ACDRs. 58.7% (54) were males and 41.3% (38) were females. Maculopapular rash was seen in 65.2% (60) cases, urticaria was seen in 15.3% (14) cases, Steven Johnson Syndrome (SJS) was seen in 9.8% (9) cases, SJS/TEN overlap was seen in 6.5% (6) cases and toxic epidermal necrolysis (TEN) was seen in 3.2% (3) case. CD4 count was below 300 in 65.3% (60) cases above 300 in 34.7% (32) cases. Gap between initiation of the treatment and onset of reaction was less than one month in 65.3% (60) cases, and more than one month in 34.7% (32) cases.

Comparative HIV-1 Proviral Dynamics in Two Individuals That Maintained Viral Replication Control with or without Antiretroviral Therapy following Superinfection.

The analysis of the HIV-1 proviral dynamics after superinfection in the context of both natural and antiretroviral therapy (ART)-mediated suppression could yield unique insights into understanding the persistence of viral variants that seeded the infected cells at different times. In this study, we performed a longitudinal analysis of the env diversity of PBMC-associated HIV DNA quasispecies in two HIV controllers (EEC09 and VC32) that were superinfected with subtype F1 viruses several years after primoinfection with subtype B viruses. Patient EEC09 started ART soon after superinfection, while patient VC32 maintained a natural control of virus replication for at least six years following the superinfection. Our analysis revealed no significant temporal changes in the overall proportion of primo-infecting and superinfecting proviral variants over 2-3 years after superinfection in both HIV controllers. Upon the introduction of ART, individual EEC09 displayed no evidence of HIV-infected cell turnover or viral evolution, while subject VC32 displayed some level of HIV-infected cell reseeding and detectable evolution (divergence) of both viral variants. These results confirm that proviral variants that seeded the reservoir at different times throughout infection could persist for long periods under fully suppressive ART or natural viremic control, but the HIV-1 proviral dynamics could be different in both settings.

A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.

Neurocognitive impairment (NCI) associated with HIV infection of the brain impacts a large proportion of people with HIV (PWH) regardless of antiretroviral therapy (ART). While the number of PWH and severe NCI has dropped considerably with the introduction of ART, the sole use of ART is not sufficient to prevent or arrest NCI in many PWH. As the HIV field continues to investigate cure strategies, adjunctive therapies are greatly needed. HIV imaging, cerebrospinal fluid, and pathological studies point to the presence of continual inflammation, and the presence of HIV RNA, DNA, and proteins in the brain despite ART. Clinical trials exploring potential adjunctive therapeutics for the treatment of HIV NCI over the last few decades have had limited success. Ideally, future research and development of novel compounds need to address both the HIV replication and neuroinflammation associated with HIV infection in the brain. Brain mononuclear phagocytes (MPs) are the primary instigators of inflammation and HIV protein expression; therefore, adjunctive treatments that act on MPs, such as immunomodulating agents, look promising. In this review, we will highlight recent developments of innovative therapies and discuss future approaches for HIV NCI treatment.

HIV and Mediterranean Zoonoses: A Review of the Literature.

A zoonosis is an infectious disease that has jumped from a non-human animal to humans. Some zoonoses are very common in the Mediterranean area and endemic in specific regions, so they represent an important problem for public health. Human Immunodeficiency Virus (HIV) is a virus that has originated as a zoonosis and is now diffused globally, with the most significant numbers of infected people among the infectious diseases. Since the introduction of antiretroviral therapy (ART), the history for people living with HIV (PLWH) has changed drastically, and many diseases are now no different in epidemiology and prognosis as they are in not-HIV-infected people. Still, the underlying inflammatory state that is correlated with HIV and other alterations related to the infection itself can be a risk factor when infected with other bacteria, parasites or viruses. We reviewed the literature for infection by the most common Mediterranean zoonoses, such as Campylobacter, Salmonella, Brucella, Rickettsia, Borrelia, Listeria and Echinococcus, and a possible correlation with HIV. We included Monkeypox, since the outbreak of cases is becoming a concern lately. We found that HIV may be related with alterations of the microbiome, as for campylobacteriosis, and that there are some zoonoses with a significant prevalence in PLWH, as for salmonellosis.

A comparison of lung cancer in HIV-positive and HIV-negative populations.

Background Lung cancer is the most common cancer worldwide and is the greatest contributor to malignancy-associated deaths. Human immunodeficiency virus (HIV) is an epidemic in many developing countries and South Africa carries the largest burden of this disease in the world. With the introduction of antiretroviral therapy (ART), acquired immune deficiency syndrome (AIDS)-defining malignancies (ADMs) are on the decline and non-AIDS-defining malignancies (NADMs) are becoming more common, with lung cancer being the most common among these. Objectives To describe and compare a cohort of HIV-positive lung cancer patients and a cohort of HIV-negative lung cancer patients. Methods A retrospective study of 188 patients with histologically confirmed bronchogenic carcinoma was conducted. Smoking history, cancer sub-type, cancer stage, HIV parameters and demographic data were collected. Results There were 31 (16.94%) HIV-positive patients. They presented at a younger age (53.94 years) than the HIV-negative group (61.64 years) (p=0.0001). Adenocarcinoma was the most common sub-type in the HIV-negative cohort while squamous cell carcinoma was slightly more common in the HIV-positive cohort. Both groups predominantly presented with locally advanced or metastatic disease. Conclusion HIV-positive patients present at a younger age than HIV-negative patients and both groups show a male-predominant pattern.

Clinicopathological correlation of kidney disease in HIV infection pre- and post-ART rollout.

The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence of HIV-associated nephropathy (HIVAN). More recently, the spectrum of disease additionally reflects comorbid illness in the ageing HIV population and ART-related nephrotoxicity. We performed a clinicopathological correlation of kidney disease in HIV-positive individuals who underwent kidney biopsy between 1989 and 2014, utilizing the 2018 Kidney Disease Improving Global Outcomes pathologic classification. ART rollout began in 2004 in South Africa. Patients biopsied pre-ART rollout were compared to those biopsied post-ART rollout with respect to demographics, clinical parameters and histology. We assessed kidney survival in a cohort of these patients following biopsy. Six hundred and ninety biopsies were included, 99 (14.3%) were undertaken pre- and 591 (85.7%) post-ART rollout. Most patients were of Black African descent (97.5%). The post-ART rollout patients were older (p = 0.007), had higher eGFR at presentation (p = 0.016) and fewer presented with eGFR of less than 15ml/min/1.73m2 (p = 0.0008). There was a decrease in the prevalence of classic HIVAN (p = 0.00001); and an increase in FSGS (NOS) in the setting of HIV (p = 0.0022) and tubulointerstitial diseases (p = 0.009) post-ART rollout. Kidney function survival over 5 years was poorest in patients with classic HIVAN (p = 0.00005) and best in minimal change nephropathy (p = 0.0013). Kidney biopsy is crucial for the correct diagnosis and management of HIV-related kidney disease. ART rollout has shifted the spectrum of kidney disease away from classic HIVAN but has not eliminated it. Histological diagnosis prognosticates kidney survival.

HIV and AIDS-defining opportunistic illnesses in the state of Qatar: A cohort population-based retrospective study covering 17 years (2000-2016)

Background and introductionHuman immune deficiency virus (HIV) infection remains a major health problem since discovery of the virus in 1981. Globally, since introduction of antiretroviral therapy, AIDS-related mortality was reduced by 47% since 2010. Also, HIV-related opportunistic infections (OIs) became less common, especially with use of prophylaxis to prevent such infections. In this study, we aim to assess the incidence of HIV infection and related OIs in Qatar for 17-year period, and to assess the spectrum of these infections, risk factors and treatment outcomes. MethodsThis is a retrospective cohort study for all HIV infected patients registered in the state of Qatar from 2000 to 2016. Incidence of HIV infection and related opportunistic illness was calculated per 100,000 population. Demographic and Clinical characteristic were compared between two groups of patients with and without opportunistic illness. Resultsof 167 cases with HIV infection 54 (32.3%) had opportunistic illness. The average incidence rate of HIV infection over 17 years is 0.69 per 100,000 population, and the incidence rate for opportunistic illness is 0.27 per 100,000 population. The most common opportunistic illness is pneumocystis jirovecii pneumonia (PCP) which constituted 25% of cases, followed by cytomegalovirus (CMV) retinitis 7.2%, Tuberculosis 5.4%, Toxoplasmosis 4.2% and, less than 2% for each of Kaposi sarcoma, lymphoma and cryptococcal infection.The outcome of treatment of cases with opportunistic illness showed cure rates of 59.3%, one year relapse rates of 8.76% and overall, 90-day mortality of 3.7% however, 33.4% of patients left the country before completion of therapy.Most of our patients in both groups were of young age, majority males, and almost half of them were Qatari. The CD4 count, CD4%, CD4/CD8 ratio and viral load were statistically significant risk factors in cases with opportunistic illness with a p value < 0.05, however presence of comorbidities was lower in patients with opportunistic illness P value of 0.032. ConclusionQatar has a low prevalence rate for HIV infection and related opportunistic illness. Early diagnosis and use of antiretroviral therapy are important measures to decrease the rate of opportunistic illness.

Osteopontin is an integral pro‐fibrotic mediator of myocardial fibrosis in HIV infection.

With introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV) has transitioned to a chronic, progressive inflammatory disease, with increasing evidence of subclinical and early‐onset cardiovascular comorbidities. PWH have a greater risk and prevalence of diastolic dysfunction compared to seronegative individuals. In a clinical cohort of ART‐adherent, virally suppressed women with HIV, we showed women with HIV exhibited increased myocardial extracellular volume and reduced diastolic strain rate compared to matched seronegative women. Taken together, we hypothesize that chronic HIV infection promotes a pro‐fibrotic environment in the heart, perturbing ventricular homeostatic function. First, we utilized the highly translatable simian immunodeficiency virus (SIV)‐infected rhesus macaque model. We used three cohorts in our study: uninfected animals (SIV‐), SIV‐infected untreated animals (SIV+), and SIV‐infected animals receiving a clinically relevant ART regimen (SIV+ART). Assessing fibrosis in the left ventricle, we observed greater interstitial fibrosis in SIV+ animals compared to SIV‐ and SIV+ART animals. We identified osteopontin as a potential fibrotic signal in the heart from its role in macrophage function, as a matricellular protein, and as an immunomodulatory cytokine. We observed significant differences in post‐translational enzymatic processing of osteopontin between the three groups, and SIV+ animals showed a significant increase in full‐length osteopontin compared to SIV‐ and SIV+ART. Lastly, we used an HIV‐infected humanized mouse model to functionally inhibit osteopontin in vivo with an RNA aptamer. HIV‐infected mice exhibited greater fibrotic burden in the left ventricle of the heart compared to uninfected controls. HIV‐infected mice treated with an osteopontin‐inhibiting RNA aptamer had reduced fibrotic content in the left ventricle compared to HIV infected mice, showing similar levels to uninfected mice. Together, these data suggest that osteopontin is an integral fibrotic signal in the heart and a potential adjunctive target in reducing HIV‐associated myocardial fibrosis.

Complicaciones no infecciosas del paciente con infección por el virus de la inmunodeficiencia humana

In recent years, the increase in life expectancy since the introduction of antiretroviral therapy (ART) along with the aging of the population with HIV infection has led to growing interest in the non-infectious complications described in these patients. Of note among them are an increase in the incidence of non-AIDS-defining cancer and liver and cardiovascular complications, among others. It is currently associated with a significant morbidity and mortality. In this update, we approach the most important aspects of the main non-infectious complications that patients with HIV infection currently present with and the key aspects to evaluate during follow-up.