Duration Of Human Immunodeficiency Virus Infection Research Articles

Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans

ObjectiveThe role the human immunodeficiency virus (HIV) and antiretroviral treatment on endothelial activation, and the subsequent relationship with cardiovascular disease, is not well understood. We investigated endothelial activation, inflammatory and cardiometabolic profiles, and measures of vascular structure and function of 66 antiretroviral treated (ART), 78 never-treated (no-ART) HIV infected and 165 HIV free Africans. MethodsBlood samples were obtained for biochemical analysis and blood pressure, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) measurements were performed. ResultsThe HIV infection duration was at least five years and the treatment 2.86 ± 0.13 years. The intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) levels were elevated in the HIV infected groups compared to the controls. The odds of higher adhesion molecule levels were increased when HIV infected (especially in the no-ART group); OR no-ART vs. no-HIV: ICAM 3.92 (2.2–7.0); VCAM 16.2 (7.5–35). ICAM and VCAM associated with HIV status and interleukin-6 (IL-6) in the total group (all p < 0.01). In both HIV infected groups VCAM associated inversely with CD4 counts (no-ART: β = −0.28, p = 0.01; ART: β = −0.22, p = 0.07) and TC (no-ART: β = −0.36, p < 0.01; ART: β = −0.27, p = 0.03). The ART group had an unfavourable lipid profile compared to the no-ART group. The inflammatory markers (C-reactive protein (CRP) and IL-6), PWV and IMT did not differ between the three groups. ConclusionHIV infected Africans showed endothelial activation when compared to HIV free controls. The endothelial activation was not accompanied by increased inflammation (as measured with CRP and IL-6), arterial stiffness or sub-clinical atherosclerosis.

Nonalcoholic Steatohepatitis and Hepatic Fibrosis in HIV-1-Monoinfected Adults With Elevated Aminotransferase Levels on Antiretroviral Therapy.

Persistent aminotransferase elevations are common in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART), including those without hepatitis B or C coinfection, but their clinical significance is unknown. HIV-infected adults with aminotransferase levels elevated above the upper limit of normal for ≥6 months while receiving ART, and without chronic viral hepatitis or other known causes of chronic liver disease, underwent a detailed metabolic assessment and liver biopsy. Sixty-two HIV-infected subjects completed the study. Forty (65%) had clinically significant liver pathology, including 34 (55%) with nonalcoholic steatohepatitis (NASH) and 11 (18%) with bridging fibrosis, 10 of whom also had NASH. Nonspecific abnormalities alone were seen in 22 (35%) subjects, including mild steatosis, mild to moderate inflammation, and evidence of drug adaptation. Insulin resistance, obesity, and the presence of either of 2 minor alleles in the PNPLA3 gene were significantly associated with increased risk of NASH and fibrosis. NASH and/or fibrosis were not associated with duration of HIV infection or ART, specific antiretroviral drugs, history of opportunistic infection, immune status, or duration of aminotransferase elevation. HIV-infected adults with chronic aminotransferase elevations while receiving ART have a high rate of liver disease. Noninvasive testing can help identify liver disease in such patients, but liver biopsy is necessary to definitively identify those at risk for liver disease progression and complications. Longitudinal follow-up of this cohort will better characterize the natural history of aminotransferase elevations in this population and identify noninvasive biomarkers of liver disease progression.

Effect of HIV Infection and Antiretroviral Therapy Duration on CD4 Count, Total and Differential White Cell Count

Aims: To assess CD4 counts, total and differential white cell counts in HIV positive patients on antiretroviral treatment (ART) and those not on antiretroviral treatments with varying durations of Original Research Article Okeke et al.; ISRR, 3(1): 14-22, 2015; Article no.ISRR.2015.003 15 infection. Study Design: Case-control study. Place and Duration of Study: Nnamdi Azikiwe University Teaching Hospital Nnewi, Nigeria from March to August 2013. Methodology: We included 181 subjects; sixty HIV patients on ART with infection duration of 5 – 8 and >8 – 17 years and ART duration of 5 – 8 and >8 – 17 years; sixty HIV patients not on ART with an infection duration of 3 – 6 and >6 – 11years; and sixty-one apparently healthy individuals control. CD4 counts, total and differential white cell counts as well as Human Immunodeficiency virus (HIV) status were determined. Results: CD4 counts was significantly higher in the control compared to the ART and non-ART and lower in HIV duration of 3 – 6 years and >6 – 11 years (P 6 – 11 years both in non-ART subjects (P<.05) TWBC was also higher in female controls than male (P<.05). Conclusion: CD4 count is generally lower in HIV subjects. TWBC is elevated in non-ART, while MXD is higher in ART and non-ART subjects. There is no difference in white cell parameters for ART subjects irrespective of differences in duration of HIV infection and antiretroviral therapy.

Comparative study of preinvasive and invasive lesions of the cervix in HIV-positive and HIV-negative women

Background: Evidence suggests that Human Immunodeficiency Virus (HIV) infection is a risk factor for preinvasive and invasive lesions of cervix but confusion regarding pathogenesis and progression of cervical neoplasia in HIV-positive women still prevails. Aims : To find the incidence of cervical neoplasia in HIV positive and HIV-negative women and to study the impact of CD4 counts, duration of HIV infection, and treatment with highly active antiretroviral therapy (HAART) on the incidence of cervical lesions in HIV positive women. Materials and Methods : It was an observational case control study carried over a period of one year at the Department of Obstetrics and Gynaecology and Department of Medicine, King George Medical University, Lucknow. Cases were HIV-positive women and controls were HIV negative women. Those with previous diagnosis or treatment for cervical neoplasia, history of total hysterectomy or coexistent immunosuppressive conditions were excluded. All subjects had cervical screening by Pap smear. Colposcopy and cervical biopsy were done if indicated. Statistical Analysis Used : Chi square test, univariate, and multivariate analysis. Results: The incidence of cervical lesions in HIV-positive women (159.66 per 1000 screened women) was higher compared to HIV-negative women (15.15 per 1000 screened women) ( P 3 were associated with an increased incidence of cervical neoplasia ( P P Conclusions: Seropositivity is associated with an increased incidence of cervical lesions. This risk is further enhanced by CD4 counts less than 500/mm 3 and duration of HIV infection of more than two years.

QTc interval prolongation in HIV-negative versus HIV-positive subjects with or without antiretroviral drugs.

QTc interval prolongation signifies an increased risk of life-threatening arrhythmia and sudden cardiac death. Cardiac manifestations of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome have become increasingly important causes of morbidity and mortality. We investigated HIV-positive patients to determine the effects of HIV infection, antiretroviral drugs, and identifiable confounders on QTc prolongation. A case-control study was conducted in a rural tertiary health center in Nigeria. Data collected included demographic variables, body mass index, blood pressure, HIV status, antiretroviral treatment (ART), duration of HIV infection and treatment, CD4 T-lymphocyte count, heart rate (HR), and QT interval. QT was corrected for HR using Bazett's formula. The sample frame comprised 89 (42.4%) HIV-negative subjects (39.3% male, 60.7% female; mean age, 36.28 ± 7.03 years); 45 (21.4%) HIV-positive, ART-naïve patients (31.1% male, 68.9% female; mean age, 36.48 ± 9.12 years); and 76 (36.2%) HIV-positive patients on ART (27.6% male, 72.4% female; mean age, 39.00 ± 7.68 years). The QTc interval and resting HR were higher in HIV-positive, drug-naïve patients than in the other two groups (P < 0.001). Female sex was associated with prolonged QTc intervals in all groups. HIV-positive patients may be at higher risk of sudden cardiac death due to fatal arrhythmia secondary to QTc interval-related cardiac events. Healthcare providers should be aware that a prolonged QTc interval is a potential indicator of increased cardiovascular risk and should exercise caution in prescribing potentially QT-prolonging medications to HIV-positive patients.

Impact of HIV infection on cardiac deformation

AimThe aim of this study was to detect abnormalities in left ventricular myocardial function due to HIV (human immunodeficiency virus) infection without established cardiovascular disease. MethodsAn echocardiogram was performed in 50 asymptomatic HIV-infected patients (age 41±6 years, 64% male) and in 20 healthy individuals. Conventional echocardiography and pulsed tissue Doppler imaging (TDI) were performed according to the guidelines. The strain rate of the basal segments was obtained with color tissue Doppler and used to evaluate systolic strain rate (SRS), early diastolic strain rate (SRE) and late diastolic strain rate (SRA). Longitudinal, radial and circumferential strain were assessed by 2D speckle tracking. ResultsThe mean duration of HIV infection was 10±5 years, CD4 count was 579±286 cells/mm3, 32% had detectable viral load, and 86% were under treatment. Of the HIV-infected patients, one had grade 1 diastolic dysfunction. The groups were not different except for E wave (HIV 0.72±0.17 m/s vs. control 0.84±0.16 m/s, p=0.01), longitudinal strain (−19.5±1.9% vs. −21±2%, p=0.005), SRS (−1.1±0.28 s−1 vs. −1.3±0.28 s−1, p=0.02) and SRE (1.8±0.4 s−1 vs. 2.2±0.4 s−1, p<0.001), but only SRS (p=0.03, 95% CI 0.036; 0.67) and SRE (p=0.001, 95% CI −0.599; −0.168) had independent value. ConclusionIn an HIV-infected population without established cardiovascular disease, myocardial deformation abnormalities can be detected with strain and strain rate, revealing markers of myocardial injury.

Impact of HIV infection on cardiac deformation

AimThe aim of this study was to detect abnormalities in left ventricular myocardial function due to HIV (human immunodeficiency virus) infection without established cardiovascular disease. MethodsAn echocardiogram was performed in 50 asymptomatic HIV-infected patients (age 41±6 years, 64% male) and in 20 healthy individuals. Conventional echocardiography and pulsed tissue Doppler imaging (TDI) were performed according to the guidelines. The strain rate of the basal segments was obtained with color tissue Doppler and used to evaluate systolic strain rate (SRS), early diastolic strain rate (SRE) and late diastolic strain rate (SRA). Longitudinal, radial and circumferential strain were assessed by 2D speckle tracking. ResultsThe mean duration of HIV infection was 10±5 years, CD4 count was 579±286 cells/mm3, 32% had detectable viral load, and 86% were under treatment. Of the HIV-infected patients, one had grade 1 diastolic dysfunction. The groups were not different except for E wave (HIV 0.72±0.17 m/s vs. control 0.84±0.16 m/s, p=0.01), longitudinal strain (−19.5±1.9% vs. −21±2%, p=0.005), SRS (−1.1±0.28 s−1 vs. −1.3±0.28 s−1, p=0.02) and SRE (1.8±0.4 s−1 vs. 2.2±0.4 s−1, p<0.001), but only SRS (p=0.03, 95% CI 0.036; 0.67) and SRE (p=0.001, 95% CI −0.599; −0.168) had independent value. ConclusionIn an HIV-infected population without established cardiovascular disease, myocardial deformation abnormalities can be detected with strain and strain rate, revealing markers of myocardial injury.

Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals.

Cognitive and functional neural correlates of human immunodeficiency virus (HIV) are only partially understood at present. Variability in neural response, which has been noted in the literature, may relate to clinical factors associated with HIV, including time since HIV diagnosis, CD4 count and nadir, HIV viral load, and comorbid infectious processes, especially hepatitis C. The present investigation evaluated working memory-related functional neural activation in 26 HIV+ participants, 28 demographically matched HIV-seronegative individuals, and 8 HIV+ individuals with hepatitis C coinfection. Analyses examined impact of HIV infection duration, CD4 count and nadir, HIV viral load, and hepatitis C serostatus. Results showed that HIV-seronegative participants had fastest reaction times, and during the working memory task, HIV+ participants with hepatitis C coinfection showed strongest bias toward commission errors; however, signal detection (i.e., overall task performance) was equivalent across groups. Functional magnetic resonance imaging (fMRI) results showed HIV-related greater activation to an easier vigilance task and HIV-related lower activation to a more difficult working memory task, consistent with reduced cognitive reserve. Hepatitis C coinfection related to diffuse neural dysregulation. Correlational analyses suggested relationships of increasingly severe disease with poorer functioning in brain regions linked to error monitoring and attention regulation.

Evaluation of Human Immunodeficiency Virus Infection‐Related Left Ventricular Systolic Dysfunction by Tissue Doppler Strain Echocardiography

Cardiovascular involvement causes significant morbidity and mortality among patients with human immunodeficiency virus (HIV) infection. Since the introduction of highly active antiretroviral treatment (HAART), subtle changes in left ventricular (LV) function, which may be clinically silent, have become more pronounced in HIV patients. Echocardiographic strain imaging (SI) may detect subclinical myocardial dysfunction at an earlier stage compared with conventional echocardiography. The aim of this study was to evaluate tissue Doppler-derived LV strain and strain rate (SR) along with conventional measures of LV function in asymptomatic, stable adult HIV patients on HAART. Twenty-one patients with HIV infection (mean age: 37.8 ± 11.9 years, 11 males) who had no cardiovascular complaints and 27 healthy volunteers (mean age: 40.9 ± 5.8 years, 14 males) were enrolled. Traditional parameters including LV ejection fraction (EF) were measured along with tissue velocity imaging (TVI) and tissue Doppler SI parameters using transthoracic echocardiography. The mean duration of HIV infection was 30.8 ± 25.1 (3-120) months. The mean LVEF in HIV group was within normal limits but lower than controls (64.5% ± 10.2% vs. 72.2% ± 6.4%, P = 0.003). There were no differences in other major traditional measures, as well as TVI parameters between groups. LV systolic strain and SR parameters were impaired indicating subtle LV systolic dysfunction in HIV group. No difference in diastolic function was observed between groups. Left ventricular systolic strain parameters may be utilized to demonstrate subtle LV systolic dysfunction in asymptomatic HIV patients.

Prevalence, Awareness, Treatment, and Control Rate of Hypertension in HIV-Infected Patients: The HIV-HY Study

We aimed to assess the prevalence of hypertension in an unselected human immunodeficiency virus (HIV)-infected population and to identify factors associated with hypertension prevalence, treatment, and control. We used a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected, consecutive, HIV-infected patients. Office blood pressure was accurately measured with standard procedures. Patients were 71% men and 92% white, with a median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive. The overall prevalence of hypertension was 29.3%; high-normal pressure accounted for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were the most frequently used drugs (76.1%: monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression models, hypertension was independently predicted by traditional risk factors, including age ≥50 years, male sex, family history of cardiovascular disease, body mass index ≥25 kg/m2, previous cardiovascular events, diabetes, central obesity, and metabolic syndrome, as well as by duration of HIV infection, duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/μl. The choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors as a third antiretroviral drug was irrelevant. Hypertension affects nearly 30% of HIV adult outpatients in Italy. More than one-third of the hypertensive subjects are unaware of their condition, and more than two-thirds are uncontrolled. A higher level of attention to the diagnosis and treatment of hypertension is mandatory in this setting.

A Randomized Controlled Pilot Trial of Valacyclovir for Attenuating Inflammation and Immune Activation in HIV/Herpes Simplex Virus 2–Coinfected Adults on Suppressive Antiretroviral Therapy

Human immunodeficiency virus (HIV) is associated with increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy (ART). Herpes simplex virus type 2 (HSV-2) is a common coinfection that may contribute to this inflammation. Sixty HIV type 1 (HIV-1)/HSV-2-coinfected adults on suppressive ART were randomized 1:1:1 to 12 weeks of placebo, low-dose valacyclovir (500 mg twice daily), or high-dose valacyclovir (1 g twice daily) in this 18-week trial. Co-primary outcome measures were the percentage of activated (CD38(+)HLA-DR(+)) CD8 T cells in blood, and highly sensitive C-reactive protein, interleukin 6, and soluble intercellular adhesion molecule 1 in plasma. Secondary outcomes included additional immune, inflammatory cytokine, and endothelial activation markers. The impact of valacyclovir (both groups combined) on each outcome was estimated using treatment × time interaction terms in generalized estimating equation regression models. Participants were mostly white (75%) men who have sex with men (80%). Median age was 51 (interquartile range [IQR], 47-56) years, median duration of HIV infection was 15 (IQR, 8-21) years, median CD4 count at enrollment was 520 (IQR, 392-719) cells/µL, and median nadir CD4 count was 142 (IQR, 42-240) cells/µL. Valacyclovir was not associated with significant changes in any primary or secondary immunological outcomes in bivariate or multivariable models. Medication adherence was 97% by self-report, 96% by pill count, and 84% by urine monitoring. Eight patients had adverse events deemed possibly related to the study drug (5 placebo, 1 low-dose, 2 high-dose), and 6 patients reported at least 1 HSV outbreak (3 placebo, 3 low-dose, 0 high-dose). Valacyclovir did not decrease systemic immune activation or inflammatory biomarkers in HIV-1/HSV-2-coinfected adults on suppressive ART. NCT01176409.

Comparison of cognitive performance in HIV or HCV mono-infected and HIV–HCV co-infected patients

Our aim was to explore the interplay between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in the expression of cognitive disorders. We performed a multi-centre cross-sectional study, enrolling three groups of asymptomatic outpatients matched for age and education: (1) HIV mono-infected; (2) HCV mono-infected; (3) HIV-HCV co-infected. All subjects were subjected to the Zung depression scale and a comprehensive neuropsychological battery. A total of 50 patients for each group were enrolled. Patients in the three groups did not significantly differ in the main common demographic and clinical characteristics, except for a lower proportion of past injecting drug use (IDU) in group 1 (4%) in comparison to groups 2 (38%, p<0.001) and 3 (78%, p<0.001), a longer duration of HIV infection in group 3 in comparison to group 1 (p<0.001) and a longer duration of HCV infection in group 3 in comparison to group 2 (p=0.028). Overall, 39.3% of patients showed minor cognitive impairment, with a higher proportion in group 3 (54%) when compared to groups 1 (28%, p=0.015) or 2 (36%, p=0.108). Patients in group 3 [odds ratio (OR) 3.35, p=0.038 when compared to group 1] and those with higher depression scores (OR 1.05, p=0.017) showed an increased risk of cognitive impairment after adjusting for education and past injection drug use. In particular, group 3 showed worse performance in psychomotor speed tasks when compared to group 1 (p=0.033). A worse cognitive performance in HIV-HCV co-infected patients was observed, suggesting an additive role of the two viruses in the pathogenesis of cognitive disorders.

CD8 Encephalitis in HIV-Infected Patients Receiving cART: A Treatable Entity

Despite its overall efficacy, combined antiretroviral therapy (cART) has failed to control human immunodeficiency virus (HIV) infection of the central nervous system (CNS). New acute and chronic neurological complications continue to be reported. We conducted a retrospective study of 14 HIV-infected patients with documented encephalitis, which was initially attributed to an undetermined origin. Brain magnetic resonance imaging (MRI) uniformly revealed unusual, multiple linear gadolinium-enhanced perivascular lesions. All patients had manifested acute or subacute neurological symptoms; the brain MRIs indicating diffuse brain damage. The mean duration of HIV infection was approximately 10 years, and 8 patients were immunovirologically stable. Cerebrospinal fluid abnormalities with mildly elevated protein and pleocytosis with >90% lymphocytes, predominantly CD8, were found in all but 1 patient. The mean cerebral spinal fluid HIV load was 5949 copies/mL. Six patients reported a minor infection a few days prior to neurological symptoms, 2 patients presented criteria for the immune reconstitution inflammatory syndrome of the CNS, 2 were in virological escape, and 1 developed encephalitis after interruption of cART. Brain biopsies revealed inflammatory encephalitis associated with astrocytic and microglial activation as well as massive perivascular infiltration by polyclonal CD8(+) lymphocytes. All patients had been treated with glucocorticosteroids. The long-term therapeutic response varied from excellent, with no sequalae (n = 5), to moderate, with cognitive disorders (n = 4). The mean survival time was 8 years; however, 5 patients died within 13 months of initiation of treatment. CD8 encephalitis in HIV-infected patients receiving cART is a clinical entity that should be added to the list of HIV complications.

Risk factors for liver fibrosis among human immunodeficiency virus monoinfected patients using the FIB4 index in Morocco

To study the prevalence and risk factors of significant hepatic fibrosis in Moroccan human immunodeficiency virus (HIV) monoinfected patients. We conducted a cross-sectional study among HIV monoinfected patients (negative for hepatitis B surface antigen and hepatitis C antibody). Clinical and laboratory data were collected from the data base of the Infectious Diseases Unit in Ibn Rochd Hospital Center [age, gender, duration of HIV infection, CD4 T lymphocyte count, HIV viral load, glycemia and current or prior use of antiretroviral and antiretroviral therapy (ART) duration]. The primary outcome was a FIB4 score > 1.45. Multivariable logistic regression identified independent risk factors for FIB4 > 1.45. A FIB4 score > 1.45 was identified in 96 among 619 (15.5%). HIV monoinfected patients followed up between September 1990 and September 2012. Multivariate analysis showed that only a viral load > 75 (OR = 2.23, 95%CI: 1.36-3.67), CD4 > 200 cells/mm(3) (OR = 0.39, 95%CI: 0.21-0.72) and age at FIB4 index calculation (OR = 1.10, 95%CI: 1.07-1.13) were independently associated with the occurrence of FIB4 index (> 1.45). Gender, duration of HIV infection, glycemia, use of antiretroviral therapy and ART duration were not associated with significant fibrosis by FIB4. FIB4 score > 1.45 was found in 15.5% of Moroccan HIV monoinfected patients. Age, HIV viremia > 75 copies/mL and CD4 count > 200 cells/mm(3) are associated with liver fibrosis. Further studies are needed to explore mechanisms for fibrosis in HIV monoinfected patients.

Effect of HCV Infection on Cause-Specific Mortality After HIV Seroconversion, Before and After 1997

Individuals with human immunodeficiency virus (HIV) infection frequently also are infected with hepatitis C virus (HCV) (co-infection), but little is known about its effects on the progression of HIV-associated disease. We aimed to determine the effects of co-infection on mortality from HIV and/or acquired immune deficiency syndrome (AIDS), and hepatitis or liver disease, adjusting for the duration of HIV infection. We analyzed data from the 16 cohorts of the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) collaboration, which included information on HCV infection and cause of death. A competing-risks proportional subdistribution hazards model was used to evaluate the effect of HCV infection on the following causes of death: HIV- and/or AIDS-related, hepatitis- or liver-related, natural, and non-natural. Of 9164 individuals with HIV infection and a known date of seroconversion, 2015 (22.0%) also were infected with HCV. Of 718 deaths, 395 (55.0%) were caused by HIV infection and/or AIDS, and 39 (5.4%) were caused by hepatitis or liver-related disease. Among individuals infected with only HIV or with co-infection, the mortality from HIV infection and/or AIDS-related causes and hepatitis or liver disease decreased significantly after 1997, when combination antiretroviral therapy became widely available. However, after 1997, HIV and/or AIDS-related mortality was higher among co-infected individuals than those with only HIV infection in each risk group: injection drug use (adjusted hazard ratio [aHR], 2.43; 95% confidence interval [CI], 1.14-5.20), sex between men and women or hemophilia (aHR, 3.43; 95% CI, 1.70-6.93), and sex between men (aHR, 3.11; 95% CI, 1.49-6.48). Compared with individuals infected with only HIV, co-infected individuals had a higher risk of death from hepatitis or liver disease. Based on analysis of data from the CASCADE collaboration, since 1997, when combination antiretroviral therapy became widely available, individuals co-infected with HIV and HCV have had a higher risk of death from HIV and/or AIDS, and from hepatitis or liver disease, than patients infected with only HIV. It is necessary to evaluate the effects of HCV therapy on HIV progression.

HIV Incidence Determination in the United States: A Multiassay Approach

Accurate testing algorithms are needed for estimating human immunodeficiency virus (HIV) incidence from cross-sectional surveys. We developed a multiassay algorithm (MAA) for HIV incidence that includes the BED capture enzyme immunoassay (BED-CEIA), an antibody avidity assay, HIV load, and CD4(+) T-cell count. We analyzed 1782 samples from 709 individuals in the United States who had a known duration of HIV infection (range, 0 to >8 years). Logistic regression with cubic splines was used to compare the performance of the MAA to the BED-CEIA and to determine the window period of the MAA. We compared the annual incidence estimated with the MAA to the annual incidence based on HIV seroconversion in a longitudinal cohort. The MAA had a window period of 141 days (95% confidence interval [CI], 94-150) and a very low false-recent misclassification rate (only 0.4% of 1474 samples from subjects infected for >1 year were misclassified as indicative of recent infection). In a cohort study, annual incidence based on HIV seroconversion was 1.04% (95% CI, .70%-1.55%). The incidence estimate obtained using the MAA was essentially identical: 0.97% (95% CI, .51%-1.71%). The MAA is as sensitive for detecting recent HIV infection as the BED-CEIA and has a very low rate of false-recent misclassification. It provides a powerful tool for cross-sectional HIV incidence determination.

Genetic Diversity as a Marker for Timing Infection in HIV-Infected Patients: Evaluation of a 6-Month Window and Comparison With BED

It has been reported that the increase in human immunodeficiency virus (HIV) sequence diversity in drug resistance surveillance specimens may be used to classify the duration of HIV infection as <1 or >1 year. We describe a mixed base classifier (MBC) optimized to categorize the duration of subtype B infections as <6 or >6 months on the basis of sequences for drug resistance surveillance specimens and compared MBC findings with those of serologic methods. The behavior of the MBC was examined across a range of thresholds for calling mixed bases. MBC performance was then evaluated using either complete pol sequences or sites reflecting evolutionary pressures (HLA selection sites, sites that increased in entropy over the course of infection, and codon positions). The MBC performance was optimal when secondary peaks on the sequencing chromatogram accounted for at least 15% of the area of primary peaks. A cutoff of <0.45% mixed bases in the pol region best identified recent infections (sensitivity = 82.7%, specificity = 78.8%), with improvement achieved by analyzing only sites that increased in entropy. In an extended data set of 1354 specimens classified by BED, the optimized MBC performed significantly better than a simple MBC (agreement, 68.98% vs 67.13%). If further validated, the MBC may prove beneficial for detecting recent infection and estimating the incidence of HIV infection.

Impact of xerostomia on oral health and quality of life among adults infected with HIV‐1

The study investigated the impact of xerostomia on oral health and quality of life (QoL) among patients infected with human immunodeficiency virus (HIV) who were attending for routine HIV monitoring in Australia. This cross-sectional, self-administered questionnaire survey and oral screening (OS) included 100 subjects who were HIV positive. The OS was conducted by a dentist blinded to the subject's survey responses. Xerostomia was determined by asking the subjects a single question. Subjects with xerostomia were found to have increased caries activity and poorer QoL, especially in the psychological dimensions of the oral health impact profile. Age and duration of HIV infection were associated with xerostomia. Early diagnosis of xerostomia and intervention with preventive dental care would potentially reduce caries and improve QoL among patients infected with HIV-1. Ongoing chronic inflammation of salivary glands despite the beneficial effects of antiretroviral therapy may play a role in the etiology of xerostomia in patients infected with HIV and requires further study.

Human immunodeficiency virus and cancer. A population of HIV-infected patients at Hospital de Santa Maria and predictors of cancer.

Cancer has become a growing burden on morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals in the era of highly active antiretroviral therapy (HAART). The objectives of this study were to determine the rates and cancer predictors of a population of HIV-infected individuals and to draw some recommendations for cancer screening in these patients. This retrospective case-control study describes malignant cancers diagnosed in HIV-infected subjects at Hospital de Santa Maria and assesses cancer predictors in HIV-infected subjects using HIV-infected controls without cancer. A total of 225 patients were included in this study: 25 cancer cases and 200 controls. Eight HIV-infected controls without cancer diagnosis were selected for each cancer case. Besides cancer´s date of diagnosis and its histological type, we also recorded demographic data, medical history and HIV-related information. Cancers were grouped as AIDS-defining cancers (ADCs), and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR) and unrelated (NADC-IUR). The majority of cancer cases were diagnosed in male patients (84%). The mean age of patients was higher in NADCs, mostly in NADCs-IUR, where almost half (43%) were infected with type 2 HIV. About half (52%) of cancer cases were ADCs (32% Kaposi sarcoma, 16% non-Hodgkin's lymphoma, and 4% cervical cancer). The most common NADCs were: lung, skin and hepatocellular carcinoma (8% each). In univariate analyses, immunosuppression, HBV coinfection, smoking and alcoholism were associated with ADCs. In multivariate analysis, alcoholism and higher HIV viral load remained independent predictors of ADCs. Longer duration of HIV infection, type 2 HIV and a longer history of HAART were associated with NADCs, in univariate analyses. Besides the evident multifactorial etiology, in this study ADCs appeared to be associated with immunosuppression, while NADCs seemed to be correlated by other oncogenic mechanisms such as chronic inflammation. Based on this study, cancer screening should be performed in these patients in Portugal.

Substance abuse increases the risk of neuropathy in an HIV‐infected cohort

Human immunodeficiency virus (HIV)-infected patients commonly develop distal symmetric polyneuropathy (DSP). Age, ethnicity, and toxic exposures may influence the risk. In this study we examined the association between substance use, antiretrovirals, ethnicity, and incident neuropathy in an HIV-infected cohort. Data were obtained from the National NeuroAIDS Tissue Consortium (NNTC), an ongoing, prospective cohort started in 1998. Cox proportional hazards models were used to examine the association of substance use, demographics, neurotoxic antiretrovirals, and laboratory parameters with incident neuropathy in 636 participants who were neuropathy-free at baseline. The cumulative incidence of DSP was 41%. Substance use (P = 0.04), number of substances used (P = 0.04), and longer duration of HIV infection (P = 0.05) were associated with incident DSP, but demographic factors, use of neurotoxic antiretrovirals, and laboratory parameters were not. Substance use and longer duration of HIV infection are risk factors for DSP in HIV-infected patients. Use of multiple substances may be particularly risky.