Natural History Of Human Immunodeficiency Virus Infection Research Articles

Maternal and Perinatal Outcomes in Pregnancies Associated with HIV Infection: A Prospective Cohort Study

Introduction: Human Immunodeficiency Virus (HIV) has persisted as the world’s leading infectious killer disease. Globally, around 19.3 million women in the reproductive age group are suffering from HIV, and most of these women are capable of transmitting this infection to their babies. Although pregnancy does not have an adverse effect on the natural history of HIV infection in women, Acquired Immunodeficiency Syndrome (AIDS) has become a leading cause of maternal and perinatal morbidity and mortality in some areas as the epidemic progresses. Aim: To assess the impact of HIV infection on maternal health, the risk of vertical transmission, and neonatal complications. Materials and Methods: This prospective cohort study was conducted at the Department of Obstetrics and Gynaecology, RG Kar Medical College and Hospital, Kolkata, West Bengal, India between March 1, 2021, and August 31, 2022. The study population comprised all pregnant patients with a known positive HIV status or those diagnosed newly during routine antenatal screening at the antenatal Outpatient Department (OPD) and Prevention of Parent to Child Transmission of HIV (PPTCT) clinic, or attending obstetric emergency. After registering in the antenatal clinic, they underwent all routine investigations, including baseline CD4 count, husband’s HIV status, screening for other sexually transmitted diseases, and initiation of Antiretroviral Therapy (ART). Maternal and perinatal outcomes, such as maternal complications, risk of vertical transmission, gestational age at birth, and birth weight of the baby, were assessed throughout the antenatal period and up to six weeks post-delivery. Data were entered into a Microsoft Excel datasheet and analysed using Statistical Packages for Social Sciences (SPSS) version 22.0 software. Categorical data were represented in the form of frequencies and proportions. Chi-square test was used for significance testing, with a p-value <0.05 considered statistically significant. Results: Out of a total of 15,087 deliveries during the study period, 55 were HIV-positive cases, with a prevalence of 0.36%. Both vaginal delivery and cesarean section showed almost similar vertical transmission rates in the newborns, i.e., 4 (14%) and 4 (17%), respectively. Opportunistic infection rates were significantly higher in mothers with lower CD4 counts (<200). Mothers receiving regular ART treatment showed a lower incidence of perinatal complications, such as neonatal sepsis, perinatal asphyxia, convulsions, or perinatal death, i.e., 6 (13.63%), compared to those not on treatment, 8 (72.72%) (p-value=0.005475). Higher rates of vertical transmission were observed in patients with significantly lower Cluster of Differentiation 4 (CD4) counts, 5 (71%) versus 3 (6.8%) (p-value=0.00001). Conclusion: Pregnancy outcomes in terms of maternal risks of infection, risk of vertical transmission, preterm births, foetal deaths, and neonatal complications can be significantly improved by early diagnosis and treatment of HIV infection. Proper antenatal care, early detection, initiation of antiretroviral drugs, and patient compliance with the multidrug regimen are the mainstay of feto-maternal well-being.

New insights into pathogenesis point to HIV-1 Tat as a key vaccine target.

Despite over 30 years of enormous effort and progress in the field, no preventative and/or therapeutic vaccines against human immunodeficiency virus (HIV) are available. Here, we briefly summarize the vaccine strategies and vaccine candidates that in recent years advanced to efficacy trials with mostly unsatisfactory results. Next, we discuss a novel and somewhat contrarian approach based on biological and epidemiological evidence, which led us to choose the HIV protein Tat for the development of preventive and therapeutic HIV vaccines. Toward this goal, we review here the role of Tat in the virus life cycle as well as experimental and epidemiological evidence supporting its key role in the natural history of HIV infection and comorbidities. We then discuss the preclinical and clinical development of a Tat therapeutic vaccine, which, by improving the functionality and homeostasis of the immune system and by reducing the viral reservoir in virologically suppressed vaccinees, helps to establish key determinants for intensification of combination antiretroviral therapy (cART) and a functional cure. Future developments and potential applications of the Tat therapeutic vaccine are also discussed, as well as the rationale for its use in preventative strategies. We hope this contribution will lead to a reconsideration of the current paradigms for the development of HIV/AIDS vaccines, with a focus on targeting of viral proteins with key roles in HIV pathogenesis.

Prevalence and risk factors for hepatitis c virus co-infection among human immunodeficiency virus-infected patients and effect of hepatitis c virus infection on acquired immunodeficiency syndrome cases at baseline.

Background:Hepatitis C virus (HCV) co-infection with human immunodeficiency virus (HIV) exists as both viruses have the common routes of transmission. HIV infection has adverse effect on the natural history of HCV infection; however, the effect of HCV infection on the natural history of HIV infection is unclear.Materials and Methods:This study was cross-sectional comprising of treatment-naïve adult HIV-infected patients attending clinics at Usmanu Danfodiyo University Teaching Hospital, Sokoto and Specialist Hospital Sokoto. The study participants were screened for HCV anti]body and assayed for transaminases and CD4+ T-lymphocytes count levels. The symptoms of acquired immunodeficiency syndrome (AIDS)-defining illnesses were asked among the study participants. The questionnaire was used for the collection of data, and SPSS software version 20 was used for the analysis of data. Student's t-tests, Pearson’s, Chi-square, and Fisher's exact tests were used for the statistical analysis, and P < 0.05 was considered statistically significant.Results:The prevalence of HIV/HCV co-infection was 20.6%. Self-intravenous drugs usage was not statistically significant (P = 0.210). HIV mono-infected patients had significantly lower alanine aminotransferase levels compared to HIV/HCV co-infected study participants (P = 0.048). AIDS status at the baseline was comparable between HIV mono-infected and HIV/HCV co-infected study participants. (P = 0.227; 0.200; 0.130).Conclusion:Moderately high prevalence of HIV/HCV co-infection was observed in the current study. HCV co-infection had no effect on AIDS status at baseline. There is a need for routine screening of HCV infection in HIV-infected individuals.

HIV, Aging, and Viral Coinfections: Taking the Long View

Viral suppression of human immunodeficiency virus (HIV) with combination antiviral therapy (cART) has led to increasing longevity but has not enabled a complete return to health among aging HIV-infected individuals (HIV+). Viral coinfections are prevalent in the HIV+ host and are implicated in cancer, liver disease, and accelerated aging. We must move beyond a simplistic notion of HIV becoming a "chronic controllable illness" and develop an understanding of how viral suppression alters the natural history of HIV infection, especially at the intersection of HIV with other common viral coinfections in the context of an altered, aging immune system.

Encefalitis por virus de inmunodeficiencia humana, reporte de un caso y revisión de tema

En este artículo se presenta el caso de un paciente con diagnóstico histológico de encefalitis por virus de inmunodeficiencia humana - (VIH), con múltiples coinfecciones incluyendo oportunistas. Es un caso llamativo, pues claramente la incidencia de dicha enfermedad ha decrecido ostensiblemente en la era post terapia antiretroviral de gran efectividad (TARGA). Es un paciente masculino heterosexual de 63 años con conductas sexuales de riesgo, que ingresó a un hospital de cuarto nivel con síntomas respiratorios y durante su hospitalización se le diagnosticó VIH / SIDA estadio C3, múltiples infecciones tales como: hepatitis B, neurosífilis, criptococosis sistémica, toxoplasmosis cerebral, histoplasmosis cutánea, candidiasis y herpes oral; recibió tratamiento y falleció 27 días después por criptococosis diseminada. Se le practicó autopsia y se observó en sustancia blanca del sistema nervioso central numerosos nódulos microgliales, linfocitos perivascular y células gigantes multinucleadas sin formación de granulomas, característicos de la encefalitis por VIH. Este paciente es un ejemplo de la historia natural por VIH en estadío avanzado con compromiso del sistema nervioso central.

HIV/HBV Coinfection

Hepatitis B and human immunodeficiency virus (HIV) infections share transmission patterns and risk factors, which explains high prevalence of chronic hepatitis B virus (HBV) infection in HIV-infected patients. Furthermore, thanks to combination of antiretroviral therapies, natural history of HIV infection has changed, and liver diseases became one of the top three primary causes of “non-AIDS (acquired immune deficiency syndrome)-related deaths” in people living with HIV (PLWHIV). Progress has also been achieved in the management of HBV infection with the use of nucleotide analogues having dual activity against HBV and HIV, allowing HBV viral suppression. Thus, HIV infection no longer affects the course of HBV infection. Treatment recommendations are applicated, and HIV-HBV-coinfected patients are mainly screened for HBV, assessed for liver fibrosis, and screened for hepatocellular carcinoma, even if other liver diseases can be associated (particularly hepatitis C or hepatitis D infection, alcohol abuse, non-alcoholic steatohepatitis).

Immunogenetics of HIV disease.

Host genetic factors are a major contributing factor to the inter-individual variation observed in response to human immunodeficiency virus (HIV) infection and are linked to resistance to HIV infection among exposed individuals, as well as rate of disease progression and the likelihood of viral transmission. Of the genetic variants that have been shown to affect the natural history of HIV infection, the human leukocyte antigen (HLA) class I genes exhibit the strongest and most consistent association, underscoring a central role for CD8(+) T cells in resistance to the virus. HLA proteins play important roles in T-cell-mediated adaptive immunity by presenting immunodominant HIV epitopes to cytotoxic T lymphocytes (CTLs) and CD4(+) T cells. Genetic and functional data also indicate a function for HLA in natural killer cell-mediated innate immunity against HIV by interacting with killer cell immunoglobulin-like receptors (KIR). We review the HLA and KIR associations with HIV disease and discuss the mechanisms underlying these associations.

Raising Awareness of Non-Hodgkin Lymphoma in HIV-infected Adolescents

Human immunodeficiency virus (HIV) chronically infected patients are at increased risk of developing non-Hodgkin lymphoma compared with the general population. Highly active antiretroviral therapy has had a dramatic effect on the natural history of HIV infection, reducing the incidence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma and improving overall survival. However, problems related to adherence to treatment, frequently experienced during adolescence, may increase the risk of acquired immunodeficiency syndrome-related cancers. Optimizing highly active antiretroviral therapy and monitoring noncompliant patients with persisting HIV replication should be considered by physicians who take care of these patients. We herein report 2 cases of relapsed/progressive Burkitt lymphoma in HIV vertically infected adolescents.

The mediating role of pain in substance use and depressive symptoms among Multicenter AIDS Cohort Study (MACS) participants

Pain in human immunodeficiency virus (HIV) frequently co-occurs with substance use and depression. The complex associations among patient characteristics, pain, depression, and drug use in HIV suggests a role for testing models that can account for relationships simultaneously, control for HIV status, and also test for mediation. Using structural equation modeling, the current study examined associations among pain, sociodemographics, illicit drug use, and depressive symptoms in 921 HIV-seropositive and 1019 HIV-seronegative men from the Multicenter AIDS Cohort Study, an ongoing prospective study of the natural history of HIV infection among gay/bisexual men. Longitudinal repeated measures data collected over a 6-year period were analyzed using predictive path models in which sociodemographics, HIV status, and CD4+ cell counts predicted pain, which, in turn, predicted depressive symptoms and illicit drug use. The path models did not differ substantially between HIV-seropositive and -seronegative men. Analyses using the total sample indicated that pain served both as a mediator and as a predictor of more use of cannabis, cocaine, and heroin, as well as more depressive symptoms. HIV-seropositive status predicted more use of inhaled nitrites. In this cohort, having lower CD4+ cell counts (predicted by HIV status), being African American, less educated, and older were all associated with more pain, which, in turn, was associated with more illicit drug use and more depressive symptoms. The results underscore the need for adequate pain management, particularly among vulnerable subgroups of HIV-seropositive and HIV-seronegative men to reduce the risk of drug use and depression.

Natural history of HIV infection in former plasma donors in rural China

Patients infected through commercial blood-selling practices (former plasma donors, FPDs) in China represent a unique patient population compared to individuals infected through sexual contact or intravenous drug use. FPDs all have an approximate time of human immunodeficiency virus (HIV) infection during the mid-1990s. Few studies about the natural history of HIV infection in these patients were performed. The current study focuses on characterizing the duration of asymptomatic infection as well as the time to disease and mortality of infected FPDs in China. A retrospective cohort study was conducted based on data collected from 5484 HIV-1 infected FPDs in Shangcai county, Henan province. Kaplan-Meier analysis was applied to estimate the asymptomatic duration from the time of infection to the onset of AIDS as well as the survival period from the onset of AIDS to the time of death. The estimated median asymptomatic phase was about 9.21 years, which is similar to that reported in other developing countries in Africa. The estimated median life span after the onset of symptoms was about 9.91 months, which is notably shorter than life spans reported elsewhere. This is the first large-scale retrospective study on the natural history of HIV infection in FPDs in rural China. The findings not only provide valuable insight into an understudied population, but should also serve as an important reference for patient management and care.

Tuberculosis as Part of the Natural History of HIV Infection in Developing Countries

An enhanced, refocused research agenda is critical to reducing the burden of tuberculosis (TB) in the human immunodeficiency virus (HIV) epidemic in developing countries. TB threatens HIV-infected patients before and after initiation of antiretroviral therapy, is difficult to diagnose, is rapidly fatal when it is drug resistant, and is being spread in clinics and hospitals. Research priorities include improved and point-of-care TB diagnostics; TB treatment and prevention during HIV infection, drug-resistant TB, and childhood TB; and optimization of TB and HIV program integration. With new TB diagnostics and drugs reaching approval, research must focus on effectively deploying these advancements. Research must include evaluations of individual, household, health care, and community approaches. Studies must apply implementation science to determine how to increase and adapt effective interventions to reduce TB burden in the context of HIV infection. Investment in this research will improve the lives of persons infected with HIV and contribute to efforts to reduce the global TB burden.

Coping with the HIV epidemic 1982–2007: 25‐year outcomes of the Hershey Haemophilia Cohort

Coping with the HIV epidemic 1982–2007: 25‐year outcomes of the Hershey Haemophilia Cohort

Hepatitis B virus and human immunodeficiency virus co-infection: impact on transmission and natural history of disease

There is overwhelming evidence of a strong association between human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections in areas of low endemicity for both viruses, due to shared risk factors. There is also much evidence that HIV modifies the natural history of HBV infection in these areas: co-infected individuals are more likely to be HBV chronic carriers, with higher levels of HBV infectivity, than HIV-negative individuals. Also, immunosuppression brought about by HIV infection reduces persistence of anti-HBs in previously immune and vaccinated individuals, and can cause HBV reactivation or re-infection in those previously exposed to HBV. Furthermore, HIV infection increases the risk of death from liver disease in HBV co-infected individuals, and this risk increases when these patients are treated with highly active anti-retroviral therapy. However, extensive research has found no convincing evidence that HBV impacts on the transmission and natural history of HIV infection. However, the...

Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.

Sepsis predisposition in children with human immunodeficiency virus

To review predisposition to sepsis in children infected with human immunodeficiency virus (HIV) in the era of highly active antiretroviral therapy (HAART). Summary of the literature with review by experts in the field. In industrialized regions, new diagnoses of vertically acquired HIV infection are falling due to perinatal interventions. Provision of HAART has resulted in an enlarging cohort of clinically stable HIV-infected children, with low viral loads and normal CD4 T-lymphocyte counts. Access to HAART in "developed" countries has markedly decreased the rate of progression to acquired immunodeficiency syndrome, the prevalence of organ-specific complications of HIV, the risk of recurrent sepsis, and the high early childhood mortality from HIV infection. There are currently no data on whether initiation of HAART during acute sepsis reduces short-term morbidity or mortality. Undiagnosed, antiretroviral-naive, HIV-infected infants still present sporadically with opportunistic infections such as Pneumocystis jiroveci and cytomegalovirus pneumonia. HIV-infected children have a greater burden of disease due to viral, bacterial, and fungal sepsis, and the case fatality rate for nonopportunistic infections may be greater than in non-HIV-infected children. In "developing" countries, with limited access to HAART, the natural history of HIV infection has altered very little, with the majority of infected children dying from either opportunistic or nonopportunistic disease before 3 yrs of age. Pediatric HIV infection is not a homogeneous condition in the era of HAART. Susceptibility to sepsis, morbidity, and mortality differ according to stage of disease, access to HAART, and virologic and immunologic response to treatment. These issues should be considered if HIV-infected children are to be enrolled and stratified in clinical trials.

Fifty years of multicentric Castleman's disease

Benjamin Castleman first described multicentric Castleman's disease (MCD) in a series of cases in 1954. Interest in MCD has grown in recent years following an association with human immunodeficiency virus (HIV) infection. Castleman's disease is separated into localized disease and MCD. The latter is characterized by polylymphadenopathy and multiorgan involvement. Histologically, Castleman's disease is divided into the hyalinized vascular form and a plasma cell variant, the former being more common in localized disease and the latter more common in MCD. MCD is associated with Kaposi's sarcoma herpesvirus (KSHV) infection, which is alternatively termed human herpesvirus 8 (HHV8). This virus encodes a homologue of interleukin 6 (vIL 6), which may mediate some systemic features of MCD. The diagnosis of Castleman's disease is established by biopsy and treatment is often based on published case reports only, as there are no randomized trials of therapy. Surgery has less of a role in MCD than in localized disease, but debulking by splenectomy may be useful to alleviate haematological sequelae. Systemic treatments for MCD have included chemotherapy, anti-herpesvirus treatments to reduce the KSHV viral load, highly active antiretroviral therapy (HAART) to reduce HIV viraemia and latterly monoclonal antibodies against both IL 6 and CD20. The introduction of HAART has altered the natural history of HIV infection; however, its impact on MCD is difficult to ascertain. Optimization and consensus in treatment of these patients remains a target for the future.

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

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

Therapeutic Challenges of AIDS-Related Non-Hodgkin's Lymphoma in the United States and East Africa

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. As we enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic, it is apparent that the evolution of antiretroviral therapy and the emergence of combination antiviral strategies have greatly affected the natural history of HIV infection and its neoplastic complications. For example, there may be a trend for declining incidence of AIDS-related lymphoma in the United States for the first time. However, in regions of the world where the burden of HIV infection is greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of morbidity and mortality. Treatment of lymphoma has evolved coincident with improvements in antiretroviral therapy. Infusional chemotherapy regimens may offer advantages over other regimens and schedules, but comparative trials have not been done. Clinical trial data are available on which to develop therapeutic strategies to treat this disease in East Africa where pragmatic approaches are needed. Both the differences in manifestations of HIV infection and the inherent difficulties in administering cytotoxic chemotherapy in this part of the world must be taken into consideration in planning therapeutic strategies. Improved understanding of the pathogenesis of HIV infection and lymphoma will likely yield improved therapeutic interventions as well.

Hepatitis C in patients with human immunodeficiency virus infection: diagnosis, natural history, meta-analysis of sexual and vertical transmission, and therapeutic issues.

Hepatitis C (HCV) infection occurs in as many as 33% of the patients with human immunodeficiency virus (HIV) infection. In view of their improved survival, liver disease will become more clinically significant in patients coinfected with HIV/HCV. Several studies in patients with hemophilia have shown that coinfected patients develop earlier and more severe liver disease, including hepatocellular carcinoma. In nonhemophilic cohorts, lower CD4 counts are associated with an increased prevalence of cirrhosis. However, HCV infection does not seem to alter the natural history of HIV infection in most cases. Human immunodeficiency virus coinfection in pregnant women increases the risk of perinatal HCV transmission 2-fold, with more than 25% of occurrences involving transmission of both viruses: cesarean delivery significantly decreases this risk. The expanded use of highly active antiretroviral therapy may lead to further improvement in morbidity and mortality from HIV infection. Thus, the management of coexistent HCV liver disease will need to be formulated. We suggest that alcohol be disallowed. Interferon and ribavirin in combination are likely to become the therapy of choice, particularly in coinfected patients with higher CD4 counts, lower HCV viremia, and non-1 genotype. During treatment, complete blood cell counts need to be closely monitored. Future controlled trials will determine the efficacy and safety of long-acting interferon preparations. Administration of highly active antiretroviral therapy, with the intent to prevent decreases in CD4 counts, seems crucial in stemming liver disease progression. However, some drugs have clear-cut hepatotoxic potential and patients with known liver disease should be closely monitored. Arch Intern Med. 2000;160:3365-3373.

Management of hepatitis C in the hemophilia patient

Patients with hemophilia who received clotting factor concentrates before the availability of heat-treated factors in the mid-1980s were almost universally infected with hepatitis C virus (HCV). Until recently, the clinical impact of chronic hepatitis C was largely overshadowed by human immunodeficiency virus (HIV) infection in this risk group. With recent advances in treating HIV infection, there is greater emphasis on the morbidity and mortality associated with chronic hepatitis C in the hemophilic population. A recent study from the United Kingdom demonstrated that mortality from chronic liver disease in hemophilic patients was 16.7 times greater than in the general population, and death resulting from liver cancer, 5.6 times greater. Before the advent of protease inhibitors, which can alter the natural history of HIV infection, co-infection with HIV appeared to accelerate the course of chronic hepatitis C. Levels of HCV RNA were dramatically increased after HIV seroconversion, and liver failure was found in 9% of patients, exclusively among those co-infected with HIV. HCV genotypes generally reflect the predominant genotype of the donor population, but multiple genotypes may be present. Liver biopsy may be performed safely via the percutaneous or transjugular route in hemophilic patients with chronic hepatitis C, although there is an increased cost because of the expense of factor replacement. Response to interferon in this population has been similar to that expected in the general population. Large trials are underway to evaluate the role of combination therapy with interferon and ribavirin for the treatment of patients with hemophilia and hepatitis C.