Healthy HIV-infected Patients Research Articles

High viral suppression and low attrition in healthy HIV-infected patients initiated on ART with CD4 above 500 cells/µL in a program setting in Uganda.

The World Health Organization recommends antiretroviral therapy (ART) for all HIV-infected patients at all CD4 counts. However, there are concerns that asymptomatic patients may have poorer viral suppression and high attrition. We sought to determine attrition and viral suppression among healthy HIV-infected patients initiated on ART in program settings. This cross-sectional study enrolled ART-experienced patients attending two PEPFAR-supported, high-volume clinics in Kampala, Uganda. Eligible patients were >18 years and had completed at least six months on ART. Participants were interviewed on socio-demographics, ART history and plasma viral load (VL) determined using Abbott Real-time. Predictors of viral suppression (<75 copies/ml) were determined using multivariate logistic regression. Overall, 267 participants were screened, 228 were eligible and 203 (89%) retained in care (visit within 90 days). Of the 203 participants, 115 (56.7%) were key-populations. Viral suppression was achieved in 173 patients (85%; 95% CI, 80.3%-90.1%). The factors associated with viral suppression were prior VL tests (AOR 6.98; p-value <0.001) and receiving care from a general clinic (AOR 5.41; p=0.009). Asymptomatic patients initiated on ART with high baseline CD4 counts, achieve high viral suppression with low risk of attrition. VL monitoring and clinic type are associated with viral suppression.

Oral Candida spp carriage and periodontal diseases in HIV-infected patients in Ribeirão Preto, Brazil.

ABSTRACTThe majority of HIV-infected patients develop Candida spp-associated clinical oral lesions. Studies have shown that asymptomatic oral colonization of Candida spp may lead to oral lesions or become a source of disseminated infections. The aim of this study was to verify the effects of periodontal conditions on Candida spp prevalence and Candida spp carriage in the oral cavity of HIV-infected patients compared to non-infected patients. Twenty-five patients not infected with HIV and 48 HIV-infected patients were classified according to periodontal conditions as being periodontal healthy or with periodontal disease. Candida spp carriage and classification were performed in oral rinse samples. Viral load and CD4+ T lymphocyte (CD4+L) counts were performed in blood samples from HIV-infected patients. No differences in Candida spp prevalence related to HIV status or periodontal condition were detected. However, Candida spp carriage was increased in periodontally affected HIV-infected patients when compared to periodontally healthy HIV-infected patients (p= 0.04). Periodontally healthy HIV-infected patients presented Candida spp carriage in similar levels as healthy or periodontally affected non-HIV-infected patients. Candida spp carriage was correlated with CD4+L counting in HIV-infected patients. We concluded that periodontal disease is associated with increased Candida spp carriage in HIV-infected patients and may be a predisposing factor to clinical manifestations of candidiasis.

Prevalence of subclinical cardiovascular disease in healthy HIV infected patients at the University Teaching Hospital in Lusaka, Zambia

Background : Cardiovascular diseases are among the leading cause of morbidity and mortality worldwide. The association between HIV and CVD has been established in many studies. However, information is still lacking on subclinical disease as well as its associated risk factors in this population. This study aimed at establishing the prevalence of subclinical CVD among clinically healthy HIV people attending their regular out- patient visits. It also looked at risk factors (traditional and non traditional) as well as the association of CVD to the CD4 count. Methods : we enrolled a total of 243 asymptomatic HIVinfected patients from the HIV outpatient clinic at the University Teaching Hospital. Data collected included demographic characteristics, duration of HIV infection, drug history including HAART regimen and cardiovascular risk factors (hypertension, diabetes and smoking). Clinical data included blood pressure, weight and height. Laboratory data included CD4 counts, serum creatinine, total cholesterol and triglycerides. We tested for subclinical CVD using 3 tools: Ankle Brachial Index (ABI) to measure for the presence of peripheral artery disease, 12 lead Electrocardiogram (ECG) for electrical abnormalities and transthoracic Echocardiography (ECHO), to measure abnormalities in cardiac structure and function. At analysis, patients where dichotomised into those with CD4≤350 and those with CD4>350. Results : participants characteristics were as follows: the mean age, 42 years (SD±10); 143 (58.5%) females; CD4≤350cells/ml was found in 140 (57.6%); 112(86.2%) were receiving HAART with 86.2% being on 1st line regimen. Systolic hypertension was present in 84(34.6%), diastolic hypertension in 89(36.6%) and 39.5% had creatinine clearance 140mmHg and diastolic BP >90mmHg. Conclusions : Prevalence of subclinical CVD in healthy HIV infected patients is high and those with CD4≤350 have a higher risk. Hypertension is the most important traditional CVD risk factor in this population. There is need to screen HIV patients attending their routine clinic visits for hypertension and subclinical CVD. ABI and ECG are readily available in most institutions and can be used with minimal expertise.

Prevalence of subclinical Cardiovascular Disease in healthy HIV infected patients at the University Teaching Hospital in Lusaka, Zambia

Background: Cardiovascular diseases are among the leading cause of morbidity and mortality worldwide. The association between HIV and CVD has been established in many studies. However, information is still lacking on subclinical disease as well as its associated risk factors in this population. This study aimed at establishing the prevalence of subclinical CVD among clinically healthy HIV people attending their regular out- patient visits. It also looked at risk factors (traditional and non traditional) as well as the association of CVD to the CD4 count.&#x0D; Methods: we enrolled a total of 243 asymptomatic HIVinfected patients from the HIV outpatient clinic at the University Teaching Hospital. Data collected included demographic characteristics, duration of HIV infection, drug history including HAART regimen and cardiovascular risk factors (hypertension, diabetes and smoking). Clinical data included blood pressure, weight and height. Laboratory data included CD4 counts, serum creatinine, total cholesterol and triglycerides. We tested for subclinical CVD using 3 tools: Ankle Brachial Index (ABI) to measure for the presence of peripheral artery disease, 12 lead Electrocardiogram (ECG) for electrical abnormalities and transthoracic Echocardiography (ECHO), to measure abnormalities in cardiac structure and function. At analysis, patients where dichotomised into those with CD4≤350 and those with CD4&gt;350.&#x0D; Results: participants characteristics were as follows: the mean age, 42 years (SD±10); 143 (58.5%) females; CD4≤350cells/ml was found in 140 (57.6%); 112(86.2%) were receiving HAART with 86.2% being on 1st line regimen. Systolic hypertension was present in 84(34.6%), diastolic hypertension in 89(36.6%) and 39.5% had creatinine clearance&lt;90. Diabetes and current smoking were not very common (3.3% and 2.9% respectively). High total cholesterol was found in 19(7.82%) of the participants while 37(15.23%) had high triglycerides. On ECG, ECHO and ABI, abnormalities were found in 53.9%, 44.4% and 20.2% respectively). The commonest cardiac lesion on both ECG and ECHO was left ventricular hypertrophy (27.4% and 23.3% respectively). Participants with CD4≤350 had higher prevalence of abnormalities on ECG (P=0.022) and ABI (P=0.043). Clinical factors associated with increased risk of subclinical CVD on multivariate logistical regression included CD4≤350, systolic BP&gt;140mmHg and diastolic BP &gt;90mmHg.&#x0D; Conclusions: Prevalence of subclinical CVD in healthy HIV infected patients is high and those with CD4≤350 have a higher risk. Hypertension is the most important traditional CVD risk factor in this population. There is need to screen HIV patients attending their routine clinic visits for hypertension and subclinical CVD. ABI and ECG are readily available in most institutions and can be used with minimal expertise.

Increased activated platelet-T cell conjugates in patients with HIV infection: relationship between coagulation/inflammation and T cells. (VIR10P.1171)

Abstract While antiretroviral therapies can successfully suppress HIV replication, there remains evidence of persistent immune activation, which is correlated with increased risks of all-cause mortality. Patients with elevated biomarkers of coagulation/inflammation such as IL-6, sCD14 and D-dimer (a fibrin bioproduct) are at an increased risk to develop non-AIDS defining illnesses such as cardiovascular disease. The interaction between the coagulation system and the immune system is critical for host defense; however, in HIV infection, the mechanisms underlying the ongoing activation of these pathways remains poorly understood. We hypothesized that interaction between platelets and T cells may play a role. We found that platelets from healthy controls and HIV infected patients bind to CD4 and CD8 T cells, preferentially to those with memory phenotypes. HIV infected patients showed a higher proportion of activated platelet (CD42b+CD62P+)-T cell conjugates and significantly correlated to the D-dimer levels. In vitro thrombin stimulation of PBMCs enhanced formation of platelet-T cell conjugates mediated in part by CD62P released by platelets. These data suggest that platelets can promote trafficking of T cells into injured tissues by upregulation of CD62P leading to enhanced rolling of leukocytes along vascular endothelium. In HIV infected patients, recruitment of T cells by this mechanism may promote a state of inflammation/coagulation and contribute to the pathology of the disease.

Enhanced effector function of CD8+ T cells through thrombin activation of protease-activated receptor 1 (P5108)

Abstract Disruption of vascular integrity by trauma and other tissue insult leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these two processes. The pro-inflammatory function of thrombin is mediated by activation of the Protease-activated receptor-1 (PAR-1). We found that peripheral blood effector memory CD4 and CD8 T lymphocytes expressed PAR-1, and that expression was increased in CD8 T cells from HIV-infected patients. Thrombin enhanced TcR-induced cytokine secretion (IFNγ) in CD8 T cells from healthy controls and HIV infected patients. In addition, thrombin had little chemotactic effect but it was able to inhibited chemotaxis in a CXCL9 gradient. Live microcroscopy revealed that thrombin induced chemokinesis, but not chemotaxis, of CD8 T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and cpERM (phosphorylated ezrin-radexin-moesin) proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T cell motility and production of pro-inflammatory cytokines and may allow for the accumulation of memory T cells at the site of tissue injury—a physiological mechanism of immune surveillance, inflammation and tissue repair.

The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma

Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi's sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

HIV and TB coinfection: using adjusted doses of lopinavir/ritonavir with rifampin

Evaluation of: Decloedt E, McIlleron H, Smith P, Merry C, Orrell C, Maartens G. Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir–ritonavir tablets. Antimicrob. Agents Chemother. 55(7), 3195–3200 (2011).HIV and TB coinfection is a widespread problem, especially in resource-limited settings. Interactions between drugs metabolized through cytochrome P450 enzymes and p-glycoprotein efflux pump, such as rifampin and HIV protease inhibitors, complicate the management of both pathologies when they coexist. The article by Decloedt et al. elegantly assesses the pharmacokinetics of three twice-daily escalating doses of lopinavir/ritonavir (400/100 mg, 600/150 mg and 800/200 mg), together with 600 mg daily of rifampin in 21 black African HIV-infected patients without TB. The article also reports safety, tolerability and virological outcomes after 3 weeks. Doubling lopinavir/ritonavir dose overcomes rifampin induction effect with good tolerability. However, concerns arise regarding the real interactions, tolerability and virological efficacy in HIV-TB-coinfected patients, which may differ from healthy volunteers or HIV-infected patients without TB.

Structural Cardiac Abnormalities Appear to Persist Despite ART

Although the cardiovascular complications of both HIV infection and antiretroviral therapy (ART) are under intense scrutiny these days, little attention has been paid specifically to structural and functional cardiac abnormalities. Researchers performed baseline transthoracic echocardiograms on 656 relatively healthy HIV-infected patients participating in a U.S. multicenter cohort study. Median age was 41, median current CD4 count was 462 cells/mm3, and median nadir CD4 count was 211 cells/mm3; 76% of …

Increased Levels of Platelet Microparticles in HIV-Infected Patients With Good Response to Highly Active Antiretroviral Therapy

Increased Levels of Platelet Microparticles in HIV-Infected Patients With Good Response to Highly Active Antiretroviral Therapy

PD-1 Predicts CD4 Loss Rate in Chronic HIV-1 Infection Better Than HIV RNA and CD38 But Not in Cryopreserved Samples

The immunopathogenic factor programmed cell death 1 (PD-1) was compared to CD38 and HIV RNA in predicting actual CD4+ T cell loss rate indicative for clinical progression. This cross sectional exploratory study included 50 consecutive, healthy HIV-infected patients off antiretroviral therapy (ART); 43 had the required observation times > 12 months. PD-1 and CD38 were determined on various T cell subsets by FACS analyses in fresh and later in parallel cryopreserved samples. Here more rapid progressors were relatively defined by having CD4 loss rates < median at -45.7/microl/year. PD-1 and CD38 densities in fresh blood were lower (p<0.001) in patients on ART (n=14) and seronegative controls (n=8). CD4 loss rates correlated significantly to current HIV RNA (R=-0.30), CD38 (R=-0.33) and PD-1 densities (R=-0.38) on CD8+ T cells, and best to DeltaCD38, i.e. the difference in CD38 between the PD-1+CD8+ and CD8+ subsets (R=-0.51). PD-1 was highest on the CD27+CD28-CD8+ subset with best correlation to progression (R=-0.54) in rapid progressors. Logistic regression models from HIV RNA, CD38 and PD-1 predicting rapid progression included PD-1 as best independent variable in combination with DeltaCD38 or CD38, supported by similar results from multiple regression analyses. PD-1 did not correlate with any of the other candidate variables. Cryopreservation reduced the CD38+ and PD-1+ fractions but corresponding densities became more suppressed through a non-linear loss most pronounced in CD38hi/PD-1hi cells with loss of predictive power. In conclusion, PD-1 was the best independent predictor for CD4 loss rates in fresh blood compared with CD38 and HIV RNA.

Differentially Expressed Cellular Gene Profiles between Healthy HIV-infected Koreans and AIDS Patients

Background: The global effect of HIV infection on the host cell gene expression profiles in healthy HIV-infected patients, as long-term non-progressors, remains largely unknown. To identify the cellular genes related with HIV infection and delayed disease progression in vivo, the host gene expression profiles between healthy HIV-infected Koreans and AIDS patients were investigated. Methods: Differential expression gene analysis was performed via oligonucleotide microarray with using Magic-oligo 10K chip. Ten HIV-uninfected persons and 10 HIV-infected patients (healthy HIV-infected patients vs. AIDS patients. respectively) were studied. Results: Only 10.8% (1,097 genes) of the total genes, that is, 331 up-regulated genes and 766 down- regulated genes were differentially expressed with more than a two-fold change in the HIV-infected persons as compared to those of the HIV-uninfected persons. Especially, 97 genes (8.8%) among 1,097 genes were commonly up- or down-regulated in both the healthy HIV-infected patients and the AIDS patients. 187 genes were differently expressed on the gene expression analysis between the healthy HIV-infected patients and the AIDS patients. Twenty-eight genes out of them showed very significant differences with a P value <0.01. Especially, tripartite motif (TRIM) 14 protein and interferon gamma receptor 2 were dramatically up-regulated in healthy HIV-infected patients, while death-associated protein, DNA directed RNA polymerase II polypeptide A and STAT were over-expressed in AIDS patients. Conclusion: Although this microarray study has some limitations, the above results will be helpful for performing more detailed, future functional studies on the differentially expressed genes related to HIV infection and delayed disease progression in vivo. (Korean J Hematol 2007;42:33-42.)

Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients.

Active TB in HIV-1-infected subjects is associated with increased HIV-1-related immunodeficiency and mortality. We assessed plasma viral load in HIV-1-infected patients with pulmonary TB (HIV/TB) and non-TB symptomatic HIV-1-infected patients (HIV). HIV-1 load was higher in HIV/TB compared with HIV at higher CD4 counts (> 500/microl) (P < 0.01), but not at lower CD4 counts (< 500/microl). We also evaluated the status of HIV-1 gene expression in peripheral blood mononuclear cells (PBMC) and serum from HIV/TB and CD4-matched healthy HIV-infected patients (HIV/C) by reverse transcriptase-polymerase chain reaction over a range of CD4 (> 900/microl to < 200/microl). HIV-1 RNA in serum and PBMC correlated to one another, and both were markedly higher in HIV/TB compared with HIV/C with higher CD4 counts. Also, during a longitudinal study of anti-tuberculous chemoprophylaxis in HIV-1-infected patients, 10 subjects who developed TB had serologies before, at the time, and after the diagnosis of TB. These HIV/TB patients had an increase in viral load (average 2.5-fold) at the time of diagnosis of TB (P < 0.05). Overall, these data indicate that the transcriptional activity of HIV-1 is enhanced in HIV-1-infected patients with active TB, especially during early HIV-1 disease. As TB often is an early HIV-1 opportunistic infection, it may particularly favour early viral replication and dissemination, and therefore contribute to progression of HIV-1 disease.

Immunologic changes in healthy probands and HIV infected patients after oral administration of Staphylococcus aureus 12c: a pilot study

Immunologic changes in healthy probands and HIV infected patients after oral administration of Staphylococcus aureus 12c: a pilot study

Unexplained thrombosis in HIV-infected patients receiving protease inhibitors: report of seven cases

Although HIV (human immunodeficiency virus) and AIDS (acquired immune deficiency syndrome)-associated morbidity and mortality have been reduced substantially by the addition of HIV protease inhibitor therapy (1), reports have surfaced describing unanticipated complications of treatment, including insulin resistance, diabetes, lipodystrophy, pseudoCushings syndrome, and bleeding diasthesis in patients with hemophilia (2–5). There have also been case reports of premature coronary artery disease and peripheral vascular disease associated with protease inhibitor use (6 – 8) and ascribed to protease inhibitor-induced hypercholesterolemia. Thromboembolic events are not common among patients infected with HIV and have not been reported to be associated with protease inhibitor usage. We noted several cases of deep venous thrombosis and pulmonary embolus among otherwise healthy HIV-infected patients who were recently started on protease inhibitor therapy. Consequently, we reviewed the rates of these thrombotic problems in 1,050 HIV-infected patients treated before the availability of protease inhibitor therapy, and compared the results with those in 650 patients treated after protease inhibitor therapy became available. We also report 7 patients who were followed in our clinics and who developed deep venous thrombosis with or without pulmonary embolism temporally related to the initiation of protease inhibitor therapy, 3 of whom developed recurrent thromboembolism despite use of warfarin therapy.

Predominant production of gamma interferon after a tetanus vaccine booster in healthy controls and HIV-infected patients

Predominant production of gamma interferon after a tetanus vaccine booster in healthy controls and HIV-infected patients

Predominant production of gamma interferon after a tetanus vaccine booster in healthy controls and HIV-infected patients

Predominant production of gamma interferon after a tetanus vaccine booster in healthy controls and HIV-infected patients

In vitro effects of the neuropeptide substance P on lymphocyte proliferation in healthy subjects and HIV-infected patients

In vitro effects of the neuropeptide substance P on lymphocyte proliferation in healthy subjects and HIV-infected patients