Assessment of serum cobalamin (vitamin B12) status among Human Immunodeficiency Virus (HIV) infected Nigerians with anaemia using serum methylmalonic acid

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

The Uncertain Significance of Anti–Glomerular Basement Membrane Antibody Among HIV-Infected Persons With Kidney Disease

HIV Disease and Aging

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Approximately 30 years ago, in June 1981, it was reported from theCenter forDiseaseControl andPrevention (CDC) that five, otherwise healthy, homosexual men in California had presented with pneumonia caused by Pneumocystis jiroveci pneumonia, a rare disease seen exclusively in individualswith a severely suppressed immune system. Several reports confirmed the initial observation and lent support to the possibility that a new sexually transmitted, infectious agent was circulating within the gay community in the United States. The clinical condition was named acquired immunodeficiency syndrome (AIDS). Two years later, a research team at the Institut Pasteur under the guidance of Francoise Barre-Sinoussi and Luc Montagnier isolated human immunodeficiency virus (HIV), the causative agent of AIDS, from a lymph node biopsy of a French patient. The isolation and characterization of HIV paved the way for the design of diagnosticmethods to identify the virus in blood andbloodproducts and towards the development of novel antiretroviral treatment (ART) to control HIV replication in infected patients. For their discoveries, Barre-Sinoussi and Montagnier were awarded the Nobel Prize in Physiology and Medicine in 2008.

Patients with human immunodeficiency virus (HIV) infection have sustained alterations in metabolism (lipids and insulin/glucose homeostasis) and body composition (fat distribution) that are proatherogenic (the Figure). HIV infection itself and/or its therapies may contribute to these alterations (the Table); although most effects are reversible, there are some possibly irreversible consequences of treatment. With the relative restoration to health seen in the era of highly active antiretroviral therapy (HAART), many traditional risk factors and promoters of dyslipidemia and diabetes also are present; they interact with HIV-specific inducers to worsen dyslipidemia and to increase the prevalence of insulin resistance and diabetes. Figure. Overview of the effects of HIV and its therapies on CVD risk. The contribution of traditional risk factors must be kept in mind, and they may occur with increased prevalence in people with HIV infection (eg, smoking). HIV, likely through the inflammatory response, and antiretroviral therapies independently affect many of the mediators of CVD risk. The effects on lipids are a prominent but complex example; HIV infection lowers LDL levels, but antiretroviral therapy raises LDL back up to normal levels. The bidirectional arrows indicate associations, but there is not yet adequate proof of causality. The dotted arrow between body composition and CVD indicates that body fat is known to affect the mediators such as dyslipidemia and insulin resistance but may also have a direct effect. FFA indicates free fatty acids; ARV, antiretroviral. View this table: Table. Effects of HIV Treatment These disturbances in lipid and glucose metabolism and renal disease may contribute, at least in part, to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals (the Figure). However, the relative contribution to excess CVD risk of traditional CVD risk factors, especially smoking, compared with these infection- and treatment-specific complications requires clarification. More prospective data with multivariable modeling are needed. …

Gastrointestinal Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques Is Characterized by Proinflammatory Dysregulation of the Interleukin-6-Janus Kinase/Signal Transducer and Activator of Transcription3 Pathway

Repeated exposure to HIV does not necessarily result in infection and HIV infection does not inevitably lead to the development of the AIDS. Multiple immunological and genetic features can confer resistance to HIV acquisition and progression at different steps in viral infection; a full understanding of these mechanisms could result in the development of novel therapeutic and vaccine approaches for HIV infection. In this review, we focus on the genetic mechanisms associated with resistance to HIV infection and to the progression to AIDS.

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients.

S tudies published over the past 3 years have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults. 1 These studies show that subclinical echocardiographic abnormalities independently predict adverse outcomes and identify high-risk groups to target for early intervention and therapy.The Joint United Nations Program on HIV/AIDS estimates that 36.1 million people were living with HIV infection at the end of the year 2000. 2 If 8% to 10% of patients develop symptomatic heart failure over a 2-to 5-year period, 3 then 3 million cases of HIV-related heart failure will present during that period. 1 Cardiovascular manifestations of HIV have been altered by the introduction of highly active antiretroviral therapy (HAART) regimens.On one hand, HAART has significantly modified the course of HIV disease, lengthened survival, and improved the quality of life of HIV-infected patients.On the other hand, the early data have raised concerns that HAART is associated with an increase in both peripheral and coronary arterial diseases. 1The HAART-associated changes are relevant only to the minority of HIV-infected individuals worldwide who have access to HAART.Thus, studies conducted before HAART became available remain globally applicable.In this review article, the principal HIV-associated cardiovascular manifestations will be discussed, with an emphasis on new knowledge about prevalence, pathogenesis, and treatment.

Idiopathic AIDS Enteropathy and Treatment of Gastrointestinal Opportunistic Pathogens

The human immunodeficiency virus (HIV), causing the acquired immunodeficiency syndrome (AIDS), was first reported thirty years ago. The UNAIDS published the latest statistics on the global HIV and AIDS epidemic in November 2010 and estimated that in 2009 there were 33.3 million people living with HIV/AIDS worldwide (Worldwide HIV and AIDS statistics, http://www.avert.org/worldstats.htm). While the annual number of new HIV infections has steadily declined, and the number of people receiving antiretroviral therapy increased, the HIV pandemic has so far caused the death of nearly 30 million people from AIDS-related causes. The sub-Saharan African region carries the greatest burden of this pandemic, with 22.5 million adults and children living with HIV/AIDS in 2009. In South Africa alone, there are an estimated 5.6 million HIV-infected people, more than in any other country, with almost one in three women aged 25–29, and over a quarter of men aged 30–34, living with HIV (HIV and AIDS in South Africa, http://www.avert.org/aidssouthafrica.htm). Tuberculosis (TB) is an important public health problem representing the most frequent opportunistic infection in HIV infected persons globally. In 1993, the World Health Organization (WHO) declared TB a global public health emergency, when an estimated 7-8 million cases and 1.3–1.6 million deaths occurred each year. Today, TB remains a leading cause of death in low- and middle-income countries, and the latest WHO report on global TB control indicates that there were an estimated 8.8 million incident cases and 1.4 million deaths from TB in 2010 (http://www.who.int/tb/en/). HIV infection is the greatest risk factor for acquiring Mycobacterium tuberculosis (M.tb) infection and developing TB. The devastating association between HIV and TB means that up to 1.2 million (12–14%) of the new TB cases were amongst HIV-infected people in 2010, and TB caused the death of an estimated 0.35 million HIV-infected people. The proportion of HIV-M.tb-coinfected persons is highest in Africa, with the African Region accounting for overall 82% of TB cases among people living with HIV. The risk of TB is increased during all stages of HIV infection from about 10% over a lifetime (in HIV-uninfected individuals) to as high as 30% per annum in patients with advanced HIV infection [1, 2]. These circumstances define the analysis of the immune response to TB in the context of HIV infection as a pressing research priority. This special issue is therefore devoted to HIV-associated TB. It comprises three review papers and six research papers. The first paper is a general overview of HIV-associated TB and focuses on the intersecting HIV and TB epidemics in countries with a high burden of both infections. Among the many challenges, the authors discuss the diagnosis of TB in HIV-infected patients, difficulties posed by antiretroviral drug interactions when treating HIV-M.tb-coinfected patients, and the WHO-recommended interventions collectively known as collaborative TB/HIV activities, such as HIV testing in TB patients, integration of HIV and TB services, provision of isoniazid preventive therapy (IPT), infection control, minimizing airborne transmission, and managing recurrent TB. The crucial question of when to initiate combined antiretroviral treatment (cART) in relation to TB treatment, balancing the increased risk of immune reconstitution inflammatory syndrome (IRIS) associated with early cART with the mortality associated with delaying HIV treatment, is discussed in the second review paper. TB-associated IRIS (TB-IRIS) is an important early complication of cART, reflecting the fact that the immune responses to TB may contribute to both protection and pathology. Two forms of TB-IRIS are recognized: (1) paradoxical, that occurs in patients who are established on TB treatment before cART, and manifest with recurrent or new symptoms and clinical features of TB after initiation of cART; (2) unmasking TB-IRIS, that has been defined in patients who are not receiving treatment for TB when cART is started, but present with active TB within 3 months of starting cART and show a heightened intensity of clinical manifestations with a marked inflammatory component [3, 4]. The authors conclude that there is compelling evidence that initiation of cART should not be delayed in HIV/TB-coinfected individuals. The WHO recommends the initiation of cART between 2 and 8 weeks subsequent to the initiation of TB therapy in individuals with CD4 counts <200/μL. Three publications (published since this review paper) of clinical trials in patients with HIV-associated TB [5–7] describe survival benefits and increased AIDS-free survival resulting from early cART initiation after the start of TB therapy, particularly in persons with far-advanced immunosuppression (CD4 <50/μL), while indicating that the risk of IRIS was higher with earlier than with later cART initiation. This survival benefit of early cART occurs despite the higher risk of IRIS in those started earlier and in those with a CD4 count <50/μL, and despite the fact that IRIS itself can be associated with mortality (case fatality rate of 3.2% in a recent meta-analysis) [8]. Although guidelines have been developed for resource-limited settings (3), the need to detect and appropriately treat IRIS in a timely fashion outside of a controlled clinical study environment remains a major challenge and requires further exploration. The third paper discusses the concept of “latent tuberculosis infection” in HIV-infected individuals. Immunological tests, such as tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) provide evidence of M.tb sensitization in one-third of the global population. Thus, more than two billion individuals are estimated to be latently infected with M.tb and show no clinical symptoms but live with the risk of subsequent progression to overt clinical disease, particularly in the context of coinfection with HIV. The traditional paradigm that distinguishes latent M.tb infection from active TB as two distinct compartmentalized states appears to be too simplistic. Recently, it has been suggested that clinically defined latent M.tb infection actually represents one extreme on a spectrum (of immune responses, mycobacterial metabolic activity, and bacillary numbers) that runs from elimination of live bacilli to subclinical and clinical symptomatic disease [9, 10]. The authors of this paper propose that the impact of HIV infection on this spectrum might be better conceptualized as a shift from controlled infection towards poor immune control, higher mycobacterial metabolic activity, and greater organism load, with subsequently increased risk of progression to active disease and discuss the evidence for such a model as well as the implications for interventions to control the HIV-associated TB epidemic. The six research papers and clinical studies in this special issue follow the reviews in thematic order. Thus, the fourth paper describes HIV-associated TB mortality and predictors of death and survival in a tertiary care center in Brazil; the fifth and sixth describe the paradoxical consequences of dual HIV and TB treatment (TB-IRIS) in Northern India and Uganda and their predictors, followed by approaches to diagnosing M.tb infection and TB in HIV-infected people using existing immunodiagnostic (IGRA) and proposed methods (antigen 85 reactivity). The final paper focuses on genetic factors (HLA-B∗57) and gender influencing the incidence of TB in HIV-infected persons in Bangalore, India. This issue shows that progress is being made in unravelling the spectrum of protective and pathological immune mechanisms in HIV and M.tb-coinfected persons, and the approaches and consequences of their treatment. Indeed, WHO in its 2011 report presents encouraging trends of globally declining TB incidence rates at a time of broadening therapeutic options, TB vaccine candidates in phases II and III trials, and the development of fast and precise PCR-based diagnostic tools. However, major obstacles such as poverty and its consequences and availability of and access to health care impact the HIV and M.tb pandemics, while at the same time new attention is also needed on diabetes, cigarette smoking, and air pollution as risk factors in TB endemic areas. Bold goals such as “Zero Deaths” [11], increased disease-specific funding for treatment programs, development of new diagnostics, vaccines, and biomedical and clinical progress as presented here will be needed to sustain accomplishments and further decrease the HIV and TB impact on global public health. Katalin A. Wilkinson Stephan Schwander M. Estee Torok Graeme Meintjes

P210 IBD and HIV: Does CD4 count remission hypothesis count?

Addressing HIV-1 latency with Flow-FISH: Finding, characterizing and targeting HIV-1 infected cells.

Hepatitis viruses and human immunodeficiency virus co-infection: pathogenisis and treatment