HIV-negative Adults Research Articles

Oral Human Papillomavirus Infection

OVER THE PAST 40 YEARS, HUMAN PAPILLOMAVIRUS (HPV) has been identified as an important pathogen. Upward of 100 types of HPV have been documented and broadly categorized into high-risk and low-risk subtypes on the basis of their association with high-grade dysplasia vs condylomata and mostly low-grade dysplasia, respectively. Infection with HPV, the most common sexually transmitted disease, begins with direct skin/mucosal contact and inoculation of immortalized basal lamina cells through the microabrasions that accompany sexual behaviors. As infected basal cells ascend the epidermal strata, HPV stimulates cell proliferation into condylomata or dysplasia, completes its life cycle, and sheds further virions. Although most people are able to clear the potential pathogen, others develop persistent infection, which if caused by a high-risk subtype, in particular HPV type 16 (HPV-16), may progress from low-grade dysplasia to a highgrade form and become malignant with local invasion across the basement membrane. Although HPV was initially seen as simply the cause of the common skin wart or anogenital wart and the rare skin cancer, the more widespread effect of the damaging potential of HPV was first recognized by zur Hausen et al in the late 1970s and early 1980s with studies linking cervical cancer to HPV infection; this work was recognized with the Nobel Prize in Medicine awarded in 2008. These discoveries spurred further investigation into the oncologic effects of HPV. Subsequent research has linked HPV to most squamous cell cancers of the vagina and anus; many cancers of the vulva and penis; and, more recently, oropharyngeal cancers. Human papillomavirus–positive oropharyngeal tumors are increasing in incidence and exceed the number of oropharyngeal tumors caused by the more traditional risk factors of tobacco and alcohol abuse. Following confirmation of the oncologic potential of HPV at each of these sites, surveys assessed the prevalence among the general population and high-risk groups, leading to longitudinal studies and targeted screening efforts. In this issue of JAMA, Gillison and colleagues report the first major prevalence study of oral HPV infection for the US population through analysis of National Health and Nutrition Examination Survey (NHANES) 2009-2010 data. The investigators studied 5579 participants aged 14 to 69 years who provided a 30-second oral rinse for HPV DNA polymerase chain reaction and type-specific hybridization. Study participants also provided interviewer-derived sociodemographic data and computer-assisted, self-interview– derived data about substance use and sexual history. The investigators found an overall prevalence of oral HPV infection of 6.9%. Prevalence peaked for ages 30 to 34 years and 60 to 64 years; with stratification by sex, this bimodal distribution was present only for men. Men had a higher overall HPV prevalence than women (10.1% vs 3.6%, respectively), and behaviors associated with higher oral prevalence were similar to those for HPV infection at other bodily sites: a history of sexual activity vs none, smoking, and a higher number of lifetime sexual partners. The study reports an overall HPV-16 oral prevalence of 1.0%, which is important because 85% of HPV-related oropharyngeal cancers are positive for this subtype. These results are remarkable for a number of reasons. Along with a recent study of HIV-positive and at-risk HIVnegative adults, the results allow estimation of oral HPV prevalence based on sexual experience, smoking status, and immune suppression. The general adult population has an oral HPV prevalence of 6.9% (men 10.1%, women 3.6%); at-risk HIV-negative adults, 25% (men 28%, women 18%); and HIV-positive adults, 40% (men 45%, women 35%). The corresponding oral HPV-16 prevalence rates are 1.0%, 5.3%, and 6.1%, respectively. The authors also report that the rate of HPV infection of the mouth was much lower than that at other sites in HIV-negative individuals. The prevalence of cervicovaginal HPV was 42% in women aged 14 to 59 years; penile/ scrotal HPV prevalences ranged from 14% to 51%; anal HPV prevalence rates ranged from 42% to 57% in

Risk Factors for Oral HPV Infection among a High Prevalence Population of HIV-Positive and At-Risk HIV-Negative Adults

Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals. This study was nested within the Multicenter AIDS Cohort Study (MACS; men) and Women Interagency HIV Study (WIHS; women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations in this cross-sectional analysis. Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared with HIV-negative individuals [adjusted OR = 2.1; 95% confidence interval (CI), 1.6-2.8]. Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each P(trend) < 0.01). In contrast, among HIV-positive individuals, lower CD4 T-cell count (P(trend) < 0.001) and higher number of lifetime sexual partners (P(trend) = 0.03) were strong risk factors. Oral HPV prevalence was elevated in HIV-positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV. Immunosuppression may contribute to increased persistence or progression of oral HPV infection.

Gender, HIV Status, and Psychiatric Disorders

More than 30 years after the onset of the human immunodeficiency virus (HIV) epidemic, there is no information on the prevalence of psychiatric disorders among HIV-positive individuals in the general population. We sought to compare the prevalence of 12-month psychiatric disorders among HIV-positive and HIV-negative adults stratified by sex and to examine the differential increase in risk of a psychiatric disorder as a function of the interaction of sex and HIV status. Face-to-face interviews were conducted between 2004 and 2005 with participants in the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2, a large nationally representative sample of US adults (34,653). The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. When compared with their HIV-negative same-sex counterparts, HIV-positive men were more likely to have any mood disorder (odds ratio [OR] = 6.10; 95% confidence interval [CI], 2.99-12.44), major depressive disorder/dysthymia (OR = 3.77; 95% CI, 1.16-12.27), any anxiety disorder (OR = 4.02; 95% CI, 2.12-7.64), and any personality disorder (OR = 2.50; 95% CI, 1.34-4.67). In relation to their same-sex HIV-negative counterparts, the effect of HIV status on the odds of any mood disorder (OR = 7.17; 95% CI, 2.52-20.41), any anxiety disorder (OR = 3.45; 95% CI, 1.27-9.38), and any personality disorder (OR = 2.66; 95% CI, 1.16-6.10) was significantly greater for men than women. HIV status was significantly more strongly associated with psychiatric disorders in men than in women. HIV-positive men had a higher prevalence than HIV-negative men of most psychiatric disorders. By contrast, HIV-positive women were not significantly more likely than HIV-negative women to have psychiatric disorders.

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania

Patients with tuberculosis (TB) often suffer from profound malnutrition. To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.

Timing of Plasmid Cytokine (IL-2/Ig) Administration Affects HIV-1 Vaccine Immunogenicity in HIV-Seronegative Subjects

To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig). This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5). No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) γ and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/10⁶ peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/10⁶ PBMCs (P = .003; T4 vs T5) for the IFN-γ ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4. Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies. NCT00069030.

Cognitive and Everyday Functioning in Older and Younger Adults With and Without HIV

The purpose of this study was to: (1) examine cognitive performance differences in older and younger adults with and without HIV, and (2) determine if such differences were related to a laboratory measure of instrumental activities of daily living. Ninety-eight HIV-positive (69 younger, 29 older) and 103 HIV-negative (84 younger, 19 older) adults were evaluated on a number of cognitive measures. Controlling for a number of confounders, age by HIV status interactions were found on two cognitive measures, indicating poorer cognitive performance for those aging with HIV. Poorer performance on these cognitive measures corresponded with poorer performance on the Timed Instrumental Activities of Daily Living test. These findings suggest that as adults age with HIV, they may be at risk for cognitive declines that would impair their ability to engage in activities important for maintaining independent living.

Normal Range of CD4 Cell Counts and Temporal Changes in Two HIVNegative Malawian Populations.

Longitudinal studies were carried out to determine trends in CD4 cell counts over a four year period in healthy HIV-negative adults in a rural (134 individuals) and an urban (80 individuals) site in Malawi, using TruCountTM and FACScountTM platforms. At baseline, median counts and 95% ranges were 890 (359-1954) cells per microlitre (μl) and 725 (114-1074) cells/μl respectively. 1.5% and 6% respectively had baseline counts below 350 cells/μl and 1.5% and 2.5% below 250 cells per μl. Transient dips to below 250 cells/μl were observed in seven individuals, with two individuals having persistently low CD4 counts over more than one year. Women and individuals from the urban site were significantly more likely to have “low CD4 count” (< 500 cells/μl) even when adjusted for other factors. In common with neighbouring countries, HIV-negative populations in Malawi have CD4 counts considerably lower than European reference ranges, and healthy individuals may have persistently or transiently low counts. Within Malawi, ranges differ according to the selected population.

HIV infection as a predictor of methadone maintenance outcomes in Chinese injection drug users

This paper's design is descriptive and correlational based on retrospective self-report survey data collected in Kunming city, China. The study investigated the difference between a group of Chinese HIV positive (N=36) and negative (N=131) opioid dependent adults maintained on methadone treatment. Comparisons were based on their quality of life (QOL), methadone treatment adherence, adverse symptom occurrence related to methadone treatment, and HIV-related behavior changes. No significant differences were found between the two groups in age, methadone maintenance dose, methadone adherence, sex desire, and drug craving level. Participants who were HIV positive reported significantly lower scores on physical health and total health-related qualify of life. They also reported greater engagement in injection related risk behavior before methadone treatment than those who tested HIV negative. For both groups, sexual and injection risk behavior significantly decreased following initiation of methadone treatment. A regression model revealed that those infected with HIV, associated significantly with higher likelihood of reporting constipation and lack of appetite, and higher frequency of reporting abdominal pain and nausea than HIV negative patients. The primary implication of these findings is that HIV positive persons in methadone treatment may require more focused services to meet their special HIV care and substance treatment needs.

Determinants of health-related quality of life in adults living with HIV in Vietnam

Health-related quality of life (HRQL) is a good indicator to monitor and evaluate healthcare services for adults with HIV/AIDS. This study described HRQL of adults with HIV and its determinants, and compared it with HRQL for the general population. A cross-sectional study with a national multistage sampling of households with and without HIV-positive people was conducted in 2008. Six provinces were purposively selected to represent areas of the country and progressions of HIV epidemics. Households were sampled with probability-proportional-to-size, following the selection of rural and urban districts. A total of 820 HIV-positive and HIV-negative adults (mean age: 32.5; 38.7% female) were interviewed. Among 400 HIV-positive people, 52.3% had a history of injecting drugs, and 56.3% were at AIDS stage and receiving antiretroviral treatment (ART). HRQL was measured using the EuroQOL five-dimension questionnaire (EQ-5D). Multiple regression models were purposefully constructed to examine the determinants of HRQL. The EQ-5D index and visual analog scale (VAS) score in less advanced HIV people (0.90, 69.3) and AIDS patients (0.88, 65.2) were significantly lower than those of the general population (0.96, 81.6) (p<0.001). The frequency of reported problems across EQ-5D dimensions in the HIV population (2.4–30.9%) was significantly higher than in the general population (0.7–12.1%). Compared to ART patients, those at earlier HIV stages reported having problems at similar proportions across four HRQL dimensions, except pain/discomfort, where ART patients had a significantly higher proportion. Injecting drug users taking ART perceived lower HRQL score than non-injecting drug users. Multiple regression determined that joblessness (p<0.01) and inaccessibility to health services (p<0.05) were associated with lower HRQL. In addition, involvements in self-help groups significantly improved HRQL among HIV-positive participants (p<0.05). The findings highlight the need to improve the health service referral system and enhance psychological and social supports for patients in early stages of HIV infection in Vietnam.

The contribution of HIV-discordant relationships to new HIV infections: a rebuttal

This letter responds to the previous letter about HIV discordant couples and their role in the HIV epidemic. The authors here state that the HIV discordant couples have been misclassified. Instead the HIV couples should be regarded as couples who voluntarily sought out counseling and testing. These couples indicate high interest in condition disclosure and counseling. This population does not include individuals who resisted testing disclosure or counseling. Thus this report cannot and does not attempt to discuss HIV-discordant couples who refrain from being identified.

Why Take an HIV Test? Concerns, Benefits, and Strategies to Promote HIV Testing Among Low-Income Heterosexual African American Young Adults

A qualitative study examined perceptions of HIV testing and strategies to enhance HIV testing among HIV-negative African American heterosexual young adults (ages 18-25 years). Twenty-six focus groups (13 male groups, 13 female groups) were conducted in two low-income communities (urban and rural). All sessions were audio-recorded and transcribed. Data analysis was completed using AnSWR software. Many participants expressed that learning one's HIV status, regardless of the result, was a benefit of taking an HIV test because this was perceived to produce emotional relief. Additional benefits included the avoidance of unknowingly spreading the virus, being offered treatment access if HIV-positive, and taking time to assess and modify risky sexual behaviors if HIV-negative. If diagnosed HIV-positive, HIV testing concerns included the recognition of one's mortality, the experience of social stigma, and concerns about accessing affordable treatment. Recommended promotion strategies included the use of HIV-positive individuals, pop culture icons, and the media to promote HIV testing messages.

Pharmacokinetic Parameters of Once-Daily Rilpivirine following Administration of Efavirenz in Healthy Subjects

Rilpivirine and efavirenz share metabolic pathways (CYP3A), potentially leading to drug-drug interactions. We report the pharmacokinetics, ex vivo antiviral activity and safety of rilpivirine, following efavirenz treatment. HIV-negative adults received in fixed sequence: treatment A (rilpivirine 25 mg once daily for 14 days, followed by a washout), treatment B (efavirenz 600 mg once daily for 14 days), immediately followed by treatment C (rilpivirine 25 mg once daily for 28 days). Rilpivirine pharmacokinetic profiles were determined on days 1 and 14 of treatment A and days 1, 14, 21 and 28 of treatment C. Ex vivo antiviral activity was measured in treatments A and C using an exploratory assay. Safety was evaluated throughout. From days 1 to 21, higher mean rilpivirine exposure was observed with treatment A compared with treatment C. The area under the concentration-time curve (AUC(24 h)) least squares (LS) means ratio (90% CI) for treatment C versus treatment A was 0.54 (0.46, 0.64; Day 1), 0.82 (0.75, 0.89; Day 14) and 0.84 (0.74, 0.94; Day 21). By day 28 of treatment C, the main rilpivirine pharmacokinetic parameters were similar to day 14 of treatment A (AUC(24 h) LS means ratio [90% CI], 0.91 [0.82, 1.01]), except for the minimum plasma concentration. At each time point in treatment C, samples of >80% of subjects demonstrated similar ex vivo antiviral activity compared with treatment A. All adverse events were grade 1 or 2. These results provide useful information supporting a clinical study evaluating HIV-1-positive subjects switching from efavirenz to rilpivirine.

Lack of a pharmacokinetic interaction between steady-state tipranavir/ritonavir and single-dose valacyclovir in healthy volunteers

This study assessed the single-dose pharmacokinetics of the herpes antiviral acyclovir (administered as the pro-drug valacyclovir) alone and in combination with twice-daily 200 mg ritonavir-boosted tipranavir (500 mg) at steady state. The study was an open label, one-sequence cross-over pharmacokinetic study in HIV-negative adults. Plasma drug concentrations were measured by validated LC/MS/MS assays; pharmacokinetics (AUC, C(max)) were determined using noncompartmental methods. The geometric mean ratio and 90% confidence interval [GMR, 90% CI] were used to evaluate the drug interaction. Twenty-six of 29 subjects completed the trial. With steady-state tipranavir/ritonavir, acyclovir C(max) decreased 4.9% [0.95, 0.88-1.02] and AUC increased 6.6% [1.07, 1.04-1.09]. The majority of subjects experienced at least one adverse event, most of which were mild gastrointestinal disorders. Three subjects discontinued tipranavir/ritonavir treatment as a result of drug-related increases in ALT/AST, including one subject who experienced mild upper abdominal pain. All subjects recovered without sequelae. When administered as a single dose of valacyclovir with steady-state tipranavir/ritonavir, there were no clinically important changes in acyclovir pharmacokinetics. This result indicates that valacyclovir can be co-administered safely with no dose adjustments.

Pattern of demographic risk factors in the seroprevalence of Anti-Toxopasma Gondii antibodies in HIV infected patients at the Lagos University Teaching Hospital

The Apicomplexan protozoan, Toxoplasma gondii, is a human parasite, with an ubiquitous distribution. Prevalence of the infection varies widely, depending on cultural, geographic and climatic factors. More often asymptomatic, T. gondii infection may be a severe and life-threatening disease. This study was conducted to determine the seroprevalence of Toxoplasma gondii IgG antibody (TIgG) among HIV infected persons at the Lagos University Teaching Hospital PEPFAR site, and the demographic characteristics of the study group. 460 plasma specimens were tested for TIgG antibodies by enzyme immuno assay technique and close ended questionnaires were applied on all respondents to obtain relevant data on demographics. Plasma was obtained from two study groups comprising of 380 HIV positive patients and 80 HIV negative adults who served as the control group. The overall seroprevalence was 30% in the immunocompetent control group (37.5% of the males tested and 16.7% among the females). The over all seroprevalence of TIgG antibody among the HIV positive respondents was 54% (206 Of 380). The study therefore showed statistically significant difference between the seroprevalence of TIgG antibody among the immunocompetent control group and HIV positive study group (p = 0.00356). Seroprevalence of TIgG antibody was lowest among the educated subjects (19% of subjects with tertiary education). T. gondii antibody seroprevalence for males, married respondents and rural dwellers were 70.4%, 72.3% and 69% respectively, and were all statistically significant at p < 0.000. Moreso, a significant association was observed between the seroprevalence of anti toxoplasma gondii IgG antibody and the consumption of beef among the study groups. (P < 0.0001). Socio-cultural and nutritional habits,contribute significantly to the prevalence of Toxoplasmosis and thus any effective control must be centred around these issues.

Viral and Host Factors Associated With the HIV-1 Viral Load Setpoint in Adults From Mbeya Region, Tanzania

The viral load setpoint (VLS) is an important predictor of HIV disease progression, but there is a lack of information regarding the VLS and its possible determinants in African populations. Initially HIV-negative adults from 3 distinct groups(female bar workers, females, and males from the general population)were followed for up to 4 years. The VLS was calculated for 108 seroconverters and associations of the VLS with possible risk factors were analyzed using univariate and multivariate regression. The median VLS for female bar workers, females, and males from the general population were 69,850, 28,600, and 158,000 RNA copies per milliliter, respectively. Significant associations with an elevated viral load were observed for male gender [risk ratio(RR) = 1.83, 95% confidence interval (95% CI) = 1.14 to 2.93], the expression of harmful HLA I alleles (RR = 1.73, 95% CI = 1.13 to 2.66) and multiple infection with different HIV-1 subtypes (RR =1.65, 95% CI = 1.03 to 2.66). Bar workers were considerably more often infected with different HIV-1 subtypes than participants from the general population. Our study confirms that gender and the expression of different HLA class I alleles are important determinants of the viremia at VLS, and it also corroborates an earlier finding that multiple infection with different HIV-1 subtypes is associated with a higher VLS.

Prevalence and Factors Associated with Renal Dysfunction in HIV Positive and Negative Adults at the University Teaching Hospital, in Lusaka.

Despite having the highest disease burden of HIV, Sub-Saharan Africa has limited data on HIV related kidney disease with most available data coming from the developed countries. Kidney disease is a recognised complication in HIV infected patients presenting with acute renal failure (ARF) or chronic kidney disease (CKD). This study investigated the prevalence and risk factors associated with renal dysfunction among hospitalised HIV infected patients at the University Teaching Hospital (UTH), Lusaka. We conducted a cross sectional study at the University Teaching Hospital Lusaka, in Zambia. Inclusion criteria were hospitalised patients aged 16years and above who consented to the study. Both HIV infected and uninfected patients were included in the study. After obtaining demographic information, study participants were screened for HIV upon their consenting for the test. A full clinical history and examination was done by study physician to determine factors associated with renal dysfunction. Of the 300 recruited hospitalised patients in this cross sectional study, 142(47%) were HIV infected. We observed a high prevalence of renal dysfunction among hospitalised HIV infected patients compared to uninfected patients (42% vs. 27%, adjusted OR 1.99, 95% CI 1.20-3.28). They had a twofold increased likelihood of developing kidney dysfunction (OR 1.96,95 CI%; 1.21-3.17). The presence of vomiting was strongly associated with renal dysfunction in both HIV positive (AOR 7.77, 95% CI 2.46-24-53) and negative (AOR4.83, 95%CI 1.40-16.66) subgroups. WHO stage III was associated with renal dysfunction in HIV infected patients. Tenofovir use, (a first line antiretroviral drug in Zambia) and hypotension were not significant factors associated with kidney disease after adjusting for other clinical parameters. Renal dysfunction is significantly higher among hospitalised HIV infected compared to uninfected, however tenofovir and hypotension were not associated with renal dysfunction.

High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya

BackgroundAlthough causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons ≥5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008.MethodsBlood cultures were done on patients meeting pre-defined criteria - severe acute respiratory illness (SARI), fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates.ResultsAmong 1,301 blood cultures among persons ≥5 years, 52 (4%) yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those ≥18 years than 5-17 years (6.9% versus 1.6%, p < 0.001). The highest yield was for inpatients with SARI (10%), compared with SARI outpatients (3%) and acute febrile outpatients (1%). Serotype 1 pneumococcus was most common (42% isolates) and 71% were serotypes included in the 10-valent pneumococcal conjugate vaccine (PCV10). Non-susceptibility to beta-lactam antibiotics was low (<5%), but to trimethoprim-sulfamethoxazole was high (>95%). The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61%) of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1). We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010.ConclusionsPneumococcal bacteremia rates were high among persons ≥5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral treatment for HIV and introduction of PCV10 for Kenyan children (anticipated in late 2010) result in substantial secondary benefits by reducing pneumococcal disease in adults.

CD4+ T cell depletion, immune activation and increased production of regulatory T cells in the thymus of HIV-infected individuals.

Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation.

Considerations on ankle-brachial index interpretation in HIV-1 infected patients

In a study published recently in HIV Medicine, Olalla et al. [1] measured ankle–brachial index (ABI) in 147 HIV-infected patients and found that 33 (22.4%) had an ‘altered’ ABI, according to the definition used by the authors ( 0.9 or 1.3). Thus, the prevalence of peripheral vascular disease (PAD) was much higher than in previous studies [2–4]. Whereas investigations validating ABI have found consistently that a decreased ABI ( 0.9) is a powerful predictor of death from cardiovascular causes in HIV-negative adults [5–8], the significance of high ABI (41.40) as a predictor of atherosclerosis remains controversial, and additional noninvasive diagnostic testing is needed to diagnose PAD in that setting [6]. Although clinical validation of ABI in patients with HIV is lacking, when ABI measurements were compared to carotid intima-media thickness (IMT), a well-established marker of sub-clinical atherosclerosis, only patients with low ABI had a high carotid IMT [9]. Given the usual late onset of clinical events in the course of systemic atherosclerosis, HIV clinicians would welcome disease surrogate markers. ABI is a simple, non-invasive test that may become useful for this purpose, but it should be remembered that only a low ABI ( 0.9) is a reliable indicator of systemic atherosclerosis and PAD.

Obesity and lymphocyte subsets in virologically suppressed HIV-infected patients

The prevalence of obesity is increasing among HIVpositive patients, with current estimates—20% to 30%— rivaling estimates for the general US population [1-3]. Obesity is associated with a chronic, systemic state of inflammation that may contribute to the development of many obesity-related comorbidities. Obesity increases the risk of hypertension, diabetes, myocardial infarction, heart failure, stroke, and some malignancies [4-6]. Because adipocytes are metabolically active, obesity also increases the production of a number of substances with proinflammatory or immune-modulating functions, which might mediate the adverse health effects: adipokines, such as leptin and adiponectin; C-reactive protein; interleukin (IL)-6; tumor necrosis factor–α; and IL-1-R agonist [4,7,8] .I n a large cohort study of subjects without HIV, obesity was associated with higher CD3, CD4, and CD8 counts [9]. The treatment of morbid obesity with gastric bypass surgery in HIV-negative adults has also been reported in small studies to change cytokine levels and a number of immune markers [10,11]. In the first study, abnormal CD95 antigen expression on Tcells was reversed with surgical weight loss [10]; and in the second study, C-reactive protein levels decreased significantly postsurgery as did lymphocyte subsets CD4 and CD8 [11]. Little is known about specific effects of obesity on the immune system in HIV-positive patients. The aim of our study was to explore the effects of obesity on lymphocyte subsets in HIV-positive patients with diabetes. 2. Methods We conducted a cross-sectional study in a cohort of 216 HIV-positive patients with diabetes at the CORE Center in Chicago. The study was approved by the Cook County Bureau of Health Services institutional review board. Patients were eligible for study if they were taking highly active antiretroviral therapy (HAART) and had undetectable HIV RNA for at least 6 months. We chose to include only patients who had well-controlled HIV infection, as ongoing HIV viremia is known to cause elevations in CD8 levels. The measure of obesity was based on body mass index (BMI), calculated as weight in kilograms divided by height in meters squared: normal weight, BMI 18.5 to 24.9; overweight, BMI 25 to 29.9; obese, BMI 30 to 34.9; and morbidly obese, BMI of at least 35. Our dependent variables were the white blood cell count and the following lymphocyte subgroups, defined by surface antigens: CD3 (Tcells), CD4 (helper Tcells), CD8 (cytotoxic or suppressor T cells), CD19 (B cells), and CD56 (natural killer cells). We used linear regression models to test bivariate relationships between BMI and the concentrations of the different cell types, after visually inspecting locally weighted scatterplot smoothercurvestoensurethatlinearmodelswereappropriate. Because of consistently nonlinear relationships at BMI greater than 40, we restricted the analysis to patients with a BMI of 40 or less. We then used multivariable linear models to test the same relationships after adjusting for age, sex, ethnic group, renal function (inverse of serum creatinine), hemoglobin A1c (HbA1c) (measureofaverageglucosecontrol),andthenumber of years since HIV diagnosis. To meet model distribution assumptions,wetransformeddependent,predictor,andcontrol variables to best approximate the normal distribution (square root transformations for HIV duration and CD3, CD4, CD8, and total lymphocyte counts; log transformations for BMI and