Human Immunodeficiency Virus Co-infected Individuals Research Articles

A simple high-performance liquid chromatographic assay for concurrent quantification of lumefantrine and efavirenz in human plasma from malaria–HIV co-infected individuals

BackgroundAs per current treatment guidelines, artemether-lumefantrine and efavirenz-based antiretroviral therapy are recommended drugs for falciparum malaria and human immunodeficiency virus (HIV) infections, respectively. A liquid chromatography-ultraviolet detection method for simultaneous quantification of lumefantrine and efavirenz was developed and validated for efficacy and pharmacokinetic clinical studies. Lumefantrine and efavirenz were separated using a 100 × 4.6 mm × 3 µm Fortis C18 chromatographic column, and a multistep gradient mobile phase. Calibration curves were obtained with a series of standard solutions containing known concentrations of the chemical reference of both analytes prepared concomitantly in drug-free plasma. The assay was validated within the calibration ranges of 78.125–20,000 ng/mL for lumefantrine and 187.15–24,000 ng/mL for efavirenz. Stability assessment was carried out with or without heating the quality control sample to 58 °C for 45 min. The method was employed to measure the plasma concentrations of lumefantrine and efavirenz in a study conducted among malaria-HIV co-infected patients.ResultLumefantrine and efavirenz were well separated from each other and from the biological matrix. The method demonstrated a good recovery of 72.64% for lumefantrine and 117.17% for efavirenz. The intra- and inter-day accuracy presented as 95.36–105.14% for lumefantrine and 104.11–115% for efavirenz and precision ranged from 1.15 to 6.45% for lumefantrine and 0.43 to 13.12 for efavirenz, were within ± 15% at the three quality control levels. The analytes from both quality control lots and samples collected from HIV-malaria co-infected individuals were found to be stable post-deactivation of infectious virus by heating to 58 °C for 45 min.ConclusionThe assay is accurate, precise and shown to simultaneously measure the lumefantrine and EFV in human plasma.

Direct-Acting Antivirals in the Treatment of Hepatitis C Virus (HCV)/Human Immunodeficiency Virus (HIV) Co-infected Patients: Real-Life Experience From Nepal.

BackgroundDirect-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C patients. However, the real-life data regarding its use in a human immunodeficiency virus (HIV) co-infection from a developing country is lacking. We aimed to see the efficacy of DAA in hepatitis C virus (HCV)/HIV co-infected populations.MethodsIn this prospective, observational, intention-to-treat study from Nepal, treatment-naïve patients undergoing treatment for chronic HCV in HIV co-infected individuals with DAA were studied. Patients on nevirapine were switched to efavirenz or atazanavir. Patients received sofosbuvir/ledipasvir or sofosbuvir/daclatasvir with or without ribavirine. Sustained virological response (SVR) at week 12, adverse events, and treatment compliance were evaluated. Treatment efficacy was compared between cirrhotic and non-cirrhotic patients.ResultsOf 218 patients presenting with an anti-HCV report, 181 (83%) had detectable HCV RNA. Eighty-five (85; 47%) patients were having ART at presentation. Three patients could not complete treatment due to gall stone pancreatitis and 82 completed treatment. Twenty-nine (29; 35%) were cirrhotic at presentation. Fifty-one (51; 62%) patients were genotype 3, 27 (33%) were genotype 1, three (4%) were mixed 1a/3, and one (1%) was 6. Seventy-four (74; 90%) had SVR12. Non-cirrhotics had 96% SVR compared to 79% in cirrhotics. SVR in genotype 3 was 88% while it was 93% in genotype 1.ConclusionsReal-life experience showed that the DAAs are equally effective in HCV HIV co-infected patients. In non-cirrhotic patients, the result is comparable to mono-infected patients. Genotype 3 co-infected are also difficult-to-treat patients. DAA treatment is well-tolerated in HCV/HIV co-infected patients, and there was no dropout during treatment.

Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome

Globally, a shift in the epidemiology of chronic liver disease has been observed. This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection (CHB), with the greatest burden restricted to the Western Pacific and sub-Saharan African regions. Amidst this is a growing burden of metabolic syndrome (MetS) worldwide. A disproportionate co-burden of human immunodeficiency virus (HIV) infection is also reported in sub-Saharan Africa, which poses a further risk of liver-related morbidity and mortality in the region. We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection. While the mechanistic association between CHB and MetS remains poorly resolved, the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB. Among HIV infected individuals, MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy (ART). It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection. However, this remains to be explored through rigorous longitudinal studies, especially in sub-Saharan Africa. Ultimately, there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV co-infected individuals.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

Diagnosis of Tuberculosis in HIV Co-infected Individuals: Current Status, Challenges and Opportunities for the Future.

Tuberculosis (TB) remains one of the most important causes of death among people co-infected with human immunodeficiency virus (HIV). The diagnosis of TB remains challenging in HIV co-infected individuals, due to a high frequency of smear-negative disease and high rates of extrapulmonary TB. Accurate, ease of use and rapid diagnosis of active TB are critical to the World Health Organization (WHO) End TB Strategy by 2050. Traditional laboratory techniques do not provide rapid and accurate results to effectively manage HIV co-infected patients. Over the last decade, molecular methods have provided significant steps in the fight against TB. However, many HIV co-infected patients do not have access to these molecular diagnostic tests. Given the costs closely related with confirming a TB diagnosis in HIV patients, an overtreatment for TB is used in this patient population. Nowadays, an estimated US $8 billion a year is required to provide TB treatment, which is very high compared with making an important strategy to improve the current diagnostic tests. This review focuses on current advances in diagnosing active TB with an emphasis on the diagnosis of HIV-associated TB. Also discussed are the main challenges that need to be overcome for improving an adequate initial diagnosis of active TB in HIV-positive patients.

HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches.

The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies.

Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a "special population"?

A substantial proportion of individuals with chronic hepatitis C virus (HCV) are co-infected with human immunodeficiency virus (HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals (DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

BackgroundBecause of the shared transmission routes, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HIV) is very common. Accumulated clinical evidence showed that one could alter the infectious course of the other virus in HIV and HCV co-infected individuals. However, little is known on the molecular basis of HIV/HCV interactions and their modulations on hosts.MethodsIn this study, treatment-naive HIV, HCV mono-/co-infected individuals with CD4+ T cell counts >300/μl were recruited and their gene expression profiles were investigated by microarray assays. The differentially expressed genes were identified and validated by quantitative real-time PCR (qRT-PCR). To further understand the biological meanings of the gene expression profiles in these three groups, GSEA analysis (version 2.0, Broad Institute http://www.broad.mit.edu/gsea) was performed.ResultsBy gene set enrichment analysis, we revealed that gene sets of cell cycle progression, innate immune response and some transcription factors in CD4+ T cells were mainly affected by HIV; while genes associated with GPCR signaling were the major targets of HCV. Metabolic pathways were modulated by both HCV and HIV viruses.ConclusionsThis study for the first time offers gene profiling basis for HCV/HIV mono-/co- infections in human beings. HIV infection displayed the great impact on transcription profile of CD4+ T cells in HIV/HCV co-infected individuals. Genes related to cell cycle arrest were significantly mediated by HIV which may lead to dysfunction of CD4+ T cells and acceleration of HCV-related disease progression in the co-infections.

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

BackgroundIdentifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB.MethodsArchived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility.ResultsHemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses.ConclusionsEvidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes.

Serum apoptosis markers in HIV-infected patients with human herpesvirus type 8 and herpes simplex virus type 2 co-infection

This study aimed to examine the influence of human herpesvirus type 8 (HHV-8) and herpes simplex virus type 2 (HSV-2) co-infections on apoptosis serum markers in human immunodeficiency virus (HIV)-infected patients. Sera from 110 HIV-infected and 59 HIV-uninfected individuals were analyzed for soluble Fas (sFas), sFas ligand (sFasL), caspase-8, and Bcl-2. The findings of HIV-infected patients with no co-infection (n = 37), HIV-infected patients with HHV-8 co-infection (n = 22), HIV-infected patients with HSV-2 co-infection (n = 51), and patients with HSV-2 co-infection and no HIV infection (n = 20) were compared to controls (reference group) with no HIV, HSV-2, and HHV-8 co-infections (n = 39). Soluble Fas and sFasL concentrations were the highest in HIV and HHV-8 co-infected patients (medians, 912.7 pg/ml and 74.3 pg/mL, respectively). No difference in caspase-8 concentrations was found, whereas Bcl-2 concentrations were the highest in HIV and HHV-8 co-infected individuals. Older age was associated with higher sFas (p < 0.001) and lower sFasL (p = 0.04) concentrations. In a robust regression model adjusted for age, the log-transformed sFas concentrations were significantly lower in HIV-infected patients with no co-infections (β = -0.244; p < 0.001) and higher in HIV and HHV-8 co-infected patients (β = 0.216; p = 0.012) compared to the reference group. Soluble FasL was significantly lower in HIV-infected patients with no co-infections (β = -0.284; p = 0.005) and in HIV-infected patients with HSV-2 co-infection (β = -0.381; p < 0.001) compared to the reference group. Soluble FasL was also higher in HIV and HHV-8 co-infected patients compared to controls (β = 0.248; p = 0.036). Our results suggest that HHV-8 and HSV-2 may have a significant effect on Fas-FasL-mediated apoptosis in HIV-1 patients. HHV-8 upregulates while HSV-2 downregulates sFas and sFasL.

Impact of smear microscopy results and observed therapy on tuberculosis treatment in Mombasa, Kenya

Tuberculosis (TB) treatment center at Coast Provincial General Hospital in Mombasa, Kenya. To describe TB management practices in a facility in coastal Kenya and identify factors associated with poor treatment outcomes. Retrospective review of patient treatment records from January 2008 to June 2009. Treatment outcomes of patients were classified as treatment success (cure or treatment completion) or poor treatment outcome (treatment failure, death or default). Relative risk regression was used to determine the association between exposures of interest and poor treatment outcomes. Records were obtained from a total of 183 patients: 142 (78%) had pulmonary TB, 68 (37%) were human immunodeficiency virus (HIV) infected and 81 (44%) had acid-fast bacilli (AFB) positive smear micros- copy. Most treated individuals (86%) achieved a successful treatment outcome as defined by the World Health Organization. Of those with poor treatment outcomes, 64% defaulted, 32% died, and 4% failed treatment. Initial negative AFB smear and HIV co-infection were associated with poor treatment outcomes (RR 3.32, 95%CI 1.22-8.99 and RR 4.61, 95%CI 1.69- 12.59, respectively). Strategies to accelerate accurate diagnosis of smear-negative TB and increase patient retention during treatment, especially in HIV co-infected individuals, are needed to reduce poor treatment outcomes in Kenya.

The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa

BackgroundThe convergent distribution of the Human Immunodeficiency Virus (HIV) and helminth infections has led to the suggestion that infection with helminths exacerbates the HIV epidemic in developing countries. In South Africa, it is estimated that 57% of the population lives in poverty and carries the highest burden of both HIV and helmith infections, however, the disease interactions are under-researched.MethodsWe employed both coproscopy and Ascaris lumbricoides-specific serum IgE to increase diagnostic sensitivity and to distinguish between different helminth infection phenotypes and their effects on immune responses in HIV co-infected individuals. Coproscopy was done by formol ether and Kato Katz methods. HIV positive and negative adults were stratified according to the presence or absence of A. lumbricoides and/or Trichuris trichuria eggs with or without elevated Ascaris IgE. Lymphocyte subsets were phenotyped by flow cytometry. Viral loads, serum total IgE and eosinophils were also analysed. Lymphocyte activation markers (CCR5, HLA-DR, CD25, CD38 and CD71) were determined. Non parametric statistics were used to describe differences in the variables between the subgroups.ResultsHelminth prevalence ranged between 40%-60%. Four distinct subgroups of were identified, and this included egg positive/high Ascaris-specific IgE (egg+IgEhi), egg positive/low IgE (egg+IgElo), egg negative/high IgE (egg-IgEhi) and egg negative/low IgE (egg-IgElo) individuals. The egg+IgEhi subgroup displayed lymphocytopenia, eosinophilia, (low CD4+ counts in HIV- group), high viral load (in HIV+ group), and an activated lymphocyte profile. High Ascaris IgE subgroups (egg+IgEhi and egg-IgEhi) had eosinophilia, highest viral loads, and lower CD4+ counts in the HIV- group). Egg excretion and low IgE (egg+IgElo) status demonstrated a modified Th2 immune profile with a relatively competent response to HIV.ConclusionsPeople with both helminth egg excretion and high Ascaris-IgE levels had dysregulated immune cells, high viral loads with more immune activation. A modified Th2 helminth response in individuals with egg positive stools and low Ascaris IgE showed a better HIV related immune profile. Future research on helminth-HIV co-infection should include parasite-specific IgE measurements in addition to coproscopy to delineate the different response phenotypes. Helminth infection affects the immune response to HIV in some individuals with high IgE and egg excretion in stool.

Impact of Kaposi Sarcoma–Associated Herpesvirus (KSHV) Burden and HIV Coinfection on the Detection of T Cell Responses to KSHV ORF73 and ORF65 Proteins

Cellular immune responses to Kaposi sarcoma-associated herpesvirus (KSHV), the etiological agent of KS and several other malignancies, are incompletely characterized. We assessed KSHV-specific interferon- gamma enzyme-linked immunospot responses in a cohort of 154 individuals, using overlapping peptide sets spanning the KSHV-encoded latency-associated nuclear antigen (ORF73) and the minor capsid glycoprotein (ORF65). Among KSHV-seropositive subjects, ORF73-specific responses dominated over responses to ORF65 and were preferentially detected in human immunodeficiency virus-coinfected individuals who had elevated levels of cell-associated KSHV DNA, indicating that the viral antigen burden may have been driving these responses. Responses to both ORF73 and ORF65 were also detected in several KSHV-seronegative subjects who were at increased risk for KSHV infection, which demonstrates that cellular immunity can be found in the absence of detectable humoral responses. These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions.

Human T‐cell lymphotropic virus antibody prevalence in HIV‐1‐infected individuals attending a sexual health clinic in South‐East London

Human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV) are both retroviruses with similar routes of transmission. A number of reports suggest variable clinical outcomes in HIV and HTLV co-infected individuals. There is no published information regarding the prevalence of HIV and HTLV co-infection in the UK. We therefore carried out an unlinked anonymised retrospective study to investigate the prevalence of HTLV co-infection in HIV infected patients attending a sexual health clinic in South-East London. We identified sera from 777 HIV-1 positive adults (504 male, 273 female) who had attended our sexual health clinic between January 2000 and March 2001. Serum samples stored at -20 degrees C were initially tested by HTLV-1 and HTLV-2 antibody enzyme-linked immunoassay (EIA). An immunoblot assay was carried out on reactive samples to discriminate between viral subtypes. Samples with indeterminate results were also analyzed by Western blot. The prevalence of HTLV antibody was 0.8% (five patients with HTLV-1 and one with HTLV-2). Four of the HTLV-1 co-infected patients were females born abroad, of Black African or Caribbean origin. The other HTLV-1-infected patient was a male in the Black Other ethnic group born in the UK, demonstrating that transmission may occur outside recognized areas of high endemicity. The HTLV-2 co-infected individual was a White male born in Italy, and was likely to have been infected through intravenous drug use. The results suggest HTLV antibody screening should be considered in the local HIV infected population of south London.

Prevalencia de seropositividad para Bartonella spp. en pacientes adictos a drogas por vía parenteral infectados y no infectados por el virus de la inmunodeficiencia humana

Serology is an useful tool in the diagnosis of Bartonella spp. infections in human immunodeficiency virus (HIV) seronegative patients. The value of this technique in HIV co-infected individuals is unknown. The aim of this study was to assess the prevalence of Bartonella spp. seropositivity among intravenous drugs abusers (IDA), both HIV-infected and non-infected. A retrospective seroepidemiological study was carried out among 241 IDA. One hundred and forty-seven of them were infected with HIV type 1. The titer of serum IgG antibodies against Bartonella spp. were determined. Thirty-three (14%) individuals were seropositive for Bartonella spp. Nineteen (13%) seropositive cases were found among HIV carriers and 14 (15%) among HIV uninfected people. No relationship between Bartonella spp. seropositivity and the CD4+ cell counts was found when HIV infected patients were analyzed. We have found a similar prevalence of Bartonella spp. seropositivity in HIV-infected and non HIV-infected IDA.

Human immunodeficiency virus and hepatitis C virus infections among patients attending sexually transmitted disease clinics, Regional 2, Thailand.

A cross-sectional study of 400 patients attending sexually transmitted disease (STD) clinics at The Venereal Diseases and AIDS Centers, Regional 2, Thailand, was conducted from January to December 1996 in order to investigate the antibody prevalence to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and to describe some epidemiological characteristics among HIV and HCV co-infected individuals. The studied patients were interviewed and their blood specimens were collected for determining anti-HIV and anti-HCV antibodies. The results revealed that the prevalence of anti-HIV among studied patients was 25%, while 7.5% were positive for anti-HCV. The positivity of both antibodies present in the same individuals was 3.3% (13/400 cases). The highest prevalences of anti-HIV, anti-HCV and both antibodies were found in studied patients aged 20 years or less. Patients with primary education, or lower, had relatively higher prevalence of anti-HIV and/or anti-HCV than those with higher level education. A relatively higher prevalence was found among commercial sex workers and labourers. Among 13 HIV and HCV co-infected individuals, there were four cases who had histories of sexual contact without condom use, but no history of parenteral contact. The rest (9/13) had histories of both parenteral contact and sexual contact without condom use.