History Of AIDS-defining Illness Research Articles

CD4/CD8 Ratio and Cancer Risk Among Adults With HIV.

Independent of CD4 cell count, a low CD4/CD8 ratioin people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV.

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve.

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/μL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/μL or AIDS. Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/μL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p=0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p=0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p=0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p=0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p=0.02). Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.

53. Sex and Race Disparities in Premature Mortality among People with HIV: A 21-Year Observational Cohort Study

BackgroundSince the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased; however, this trend may fail to quantify premature deaths among PWH. We assessed trends and disparities in all-cause and premature mortality by sex, HIV risk factor, and race, among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 – December 2018.MethodsWe examined mortality trends across calendar eras using person-time from clinic entry to date of death or December 31, 2018. We compared mortality rates by demographic and clinical factors and calculated adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) using multivariable Poisson regression. For individuals who died, years of potential life lost (YPLL) were obtained from the expected years of life remaining by referencing US sex-specific period life tables at age and year of death; age-adjusted YPLL (aYPLL) rates were also calculated. We examined patient factors associated with YPLL using multivariable linear regression. ResultsAmong the 6,531 individuals (51% non-Hispanic [NH] White race, 40% NH Black race, 21% female) included, 956 (14.6%) died. Mortality rates dramatically decreased during the study period (Figure). After adjusting for calendar era, age, injection drug use, hepatitis C virus (HCV), year of HIV diagnosis, history of AIDS-defining illness, CD4 cell count, and HIV RNA at clinic entry, only female sex (aIRR=1.32, 95% CI: 1.13–1.55 vs. males) but not NH Black race (aIRR=1.02, 95% CI: 0.88–1.17 vs. NH White race) was associated with increased mortality. In contrast, aYPLL per 1,000-person years was significantly higher for both female and NH Black PWH (Table 1). In adjusted models including CD4 cell count, HIV RNA, HCV, and year of clinic entry, higher YPLL remained associated with NH Black race, female sex regardless of HIV risk factor, and younger age at HIV diagnosis (Table 2). ConclusionDespite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in care in this cohort. YPLL is a useful measure for examining persistent gaps in longevity and premature mortality among PWH.Disclosures Peter F. Rebeiro, PhD, MHS, Gilead (Other Financial or Material Support, Single Honorarium for an Expert Panel)

Significant Psychosocial Influence in Frail People Living with HIV Independent of Frailty Instrument Used.

Antiretroviral therapy (ART) usage among people living with HIV (PLWH) has led to significant mortality declines and increasing lifespan. However, high incidence and early onset of aging-related conditions such as frailty, pose as a new threat to this population. We aimed to characterize frailty by comparing health domains consisting of psychosocial, functional and physical deficits between frail PLWH and matched uninfected controls; identify associated risk factors and the impact on negative health outcomes including mortality risk score, quality of life, healthcare utilization, functional disability and history of falls among virally suppressed PLWH. Cross-sectional study. Infectious disease clinic in a tertiary institution. Individuals aged >25 years, on ART >12 months, not pregnant and without acute illness; multi-ethnic, Asian. Frailty instruments included Frailty phenotype (FP), FRAIL scale (FS) and Frailty index (FI). FI health deficits were categorized into health domains (psychosocial, functional and physical) and used as standard comparator to characterize frailty. Health domains of frail PLWH were compared with frail matched, uninfected controls. Regression analyses were applied to explore associated risk factors and health-related frailty outcomes. We recruited 336 PLWH. Majority were male (83%), Chinese (71%) with CD4+ count 561 (397-738) cells/µl. Frailty prevalence among PLWH were 7% (FP); 16% (FS) and 22% (FI). Proportions of psychosocial, functional, and physical domains were similarly distributed among frail PLWH measured by different frailty instruments. When compared with matched controls, psychosocial dominance was significant among the PLWH, but not in functional and physical domains. Identified frailty risk factors included poor nutritional status, higher CD4+ count nadir, depression, metabolic syndrome, higher highly sensitive C-reactive protein (hsCRP) and history of AIDS-defining illness (ADI). Frailty influenced the risk for negative health outcomes including increased mortality risk scores, poor quality of life (QOL), frequent healthcare utilization and increased functional disability (p<0.05). This study highlighted the importance of psychosocial influence in the development of frailty among treated PLWH in a multi-ethnic, Asian setting.

Long-term trends in HIV care entry: over 15years of clinical experience from Poland.

Delay in HIV diagnosis and consequently late care entry with low CD4 counts remain a major challenge for the control of the HIV/AIDS epidemic. The aim of this study was to analyse the evolution of characteristics of the HIV epidemic in Poland. Cross-sectional data were collected for 3972 HIV-infected patients followed up in 14 of 17 Polish HIV treatment centres in the years 2000-2015. Clinical data were analysed and factors associated with late presentation (baseline CD4 count<350cells/μL or history of AIDS-defining illness) and advanced HIV disease (baseline CD4 count<200cells/μL or history of AIDS) were identified. The majority (57.6%) of patients entered care late, while 35.6% presented with advanced HIV disease. The odds of being linked to care late or with advanced HIV disease increased consistently across age categories, increasing from 2.55 [95% confidence interval (CI) 1.46-4.47] for late presentation and 3.13 (95% CI 1.49-6.58) for advanced disease for the 21-30-year-old category to 5.2 (95% CI 1.94-14.04) and 8.15 (95% CI 2.88-23.01), respectively, for individuals>60years of age. Increased risks of late entry and advanced HIV disease were also observed for injecting drug users [adjusted odds ratio (aOR) 1.74 (95% CI 1.16-2.60) and 1.55 (95% CI 1.05-2.30), respectively], with lower aOR associated with the men who have sex with men transmission route [aOR 0.3 (95% CI 0.31-0.59) and 0.39 (95% CI 0.29-0.53), respectively]. The frequencies of cases in which patients were linked to care late and with advanced HIV disease decreased over time from 67.6% (2000) to 53.5% (2015) (P<0.0001) and from 43.5% (2000) to 28.4% (2015) (P=0.001), respectively. Despite improvements over time, most patients diagnosed with HIV infection entered care late, with a third presenting with advanced HIV disease. Late care entry remains common among people who inject drugs and heterosexual groups.

Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis.

It is not known whether immune dysfunction is associated with increased risk of death after cancer diagnosis in persons with HIV (PWH). AIDS-defining illness (ADI) can signal significant immunosuppression. Our objective was to determine differences in cancer stage and mortality rates in PWH with and without history of ADI. PWH with anal, oropharynx, cervical, lung cancers, or Hodgkin lymphoma diagnoses from January 2000 to December 2009 in the North American AIDS Cohort Collaboration on Research and Design were included. Among 81,865 PWH, 814 had diagnoses included in the study; 341 (39%) had a history of ADI at time of cancer diagnosis. For each cancer type, stage at diagnosis did not differ by ADI (P > 0.05). Mortality and survival estimates for cervical cancer were limited by n = 5 diagnoses. Adjusted mortality rate ratios showed a 30%-70% increase in mortality among those with ADI for all cancer diagnoses, although only lung cancer was statistically significant. Survival after lung cancer diagnosis was poorer in PWH with ADI vs. without (P = 0.0001); the probability of survival was also poorer in those with ADI at, or before other cancers although not statistically significant. PWH with a history of ADI at lung cancer diagnosis had higher mortality and poorer survival after diagnosis compared to those without. Although not statistically significant, the findings of increased mortality and decreased survival among those with ADI (vs. without) were consistent for all other cancers, suggesting the need for further investigations into the role of HIV-related immune suppression and cancer outcomes.

Factors associated with fractures in HIV-infected persons: which factors matter?

Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk. We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV. We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43years, and 72% were male. The hepatitis C co-infection rate was 28%, about 40% had nadir CD4 count <200, and about 40% had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95% CI 0.6-1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95% CI 1.1-2.3), as did nadir CD4 count <200 (aRR 3.1, 95% CI 1.9-5.0) and history of AIDS-defining illness (aRR 1.6, 95% CI 1.1-2.2). There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.

P17.32 Risk factors for nevirapine-associated rash and/or hepatopatotoxicity among hiv-infected patients in indonesia

Introduction Nevirapine (NVP) is commonly used as a component of first-line antiretroviral therapy in Indonesia. We aimed to determine the risk factors for NVP-associated rash and/or heaptotoxicity among HIV-infected patients in Indonesia. Methods A case-control study was conducted in HIV-infected patients who developed rash after taking NVP or increasing level of transaminase enzim (case) and those who did not have rash or increasing level of transaminase enzim (control). Results A total of 149 patients with a mean (SD) age of 35.2 (10.2) years; 84 (56.4%) male, 56 (37.6%) female and 9 (6.0%) transgender were included in the study. Mean body weight (SD) was 56.7 (38.8) kg. Of all, 9 (6.0%) patients had a history of AIDS-defining illness and 12 (8.1%) patients had history of drug allergy. Mean CD4 cell counts at the time of NVP initiation was 147.3 (2–615) cells/mm3. There were 49 patients in case group and 100 patients in control group. In case group,18.4%, 73.9%, 18.4% and 18.4% of patients developed grade 1, 2, 3, and 4 of rash, 57.1%, 21.4%, 7.1% and 14.3% of patients developed grade 1, 2, 3, and 4 of hepatotoxicity, respectively. Mean time to develop rash was 19.4 (5–52) days. By logistic regression, history of drug allergy (OR, 4.20; 95% CI, 0.64–27.84) body weight (OR, 1.15; 95% CI, 0.72–1.82), CD4 cells counts (OR, 0.85; 95% CI, 0.54–1.35), and AIDS-defining illness (OR, 0.99; 95% CI, 0.38–2.56) were not significantly associated with nevirapine-associated rash and/or hepatotoxicity among HIV-infected patients in Indonesia. Conclusion In Indonesia settings where patients were initiated NVP, history of drug allergy, lower body weight, and higher CD4 cell count are not the risk factors for NVP-associated rash and/or hepatotoxicity. Disclosure of interest statement Authors declare that there is no conflict of interest regarding the publication of the paper.

Cognitive function in women with HIV: findings from the Women's Interagency HIV Study.

In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2). From 2009 to 2011, 1,521 (1,019 HIV-infected) participants from the Women's Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional. The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in well-matched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition.

A rapid progressive and fatal case of Non-Hodgkin’s lymphoma in a newly diagnosed HIV patient

Background Non-Hodgkin’s lymphoma (NHL) is one of the frequent and severe oncologic pathologies associated with HIV infection. Unlike in immunocompetent patients, this pathology manifests more aggressively in HIV-positive patients, frequently with severe systemic extranodal involvement, affecting the gastrointestinal tract, liver, bone marrow, central nervous system (CNS). Along extranodal involvement, the low level of CD4 at diagnosis, previous history of AIDS-defining illness, the NHL advanced stage, high LDH level and advanced age, are unfavorable prognostic factors for NHL associated with HIV infection.

Mean platelet volume is decreased in HIV-infected women

HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/μL (95% confidence interval (CI) 238, 259 cells/μL) vs. 276 cells/μL (95% CI 265, 287 cells/μL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.

Fracture incidence in HIV-infected women: results from the Women's Interagency HIV Study

The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited. We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women's Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture. At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P < 0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4(+) cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture. Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women

We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.

Late Presentation for Human Immunodeficiency Virus Care in the United States and Canada

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

The Association of HIV Infection with Left Ventricular Mass/Hypertrophy

Left ventricular hypertrophy (LVH) is an independent predictor of major cardiovascular events. Cardiovascular risk is increased among human immunodeficiency virus (HIV)-infected patients. To assess LV mass/hypertrophy in HIV infection, 654 women enrolled in the Women's Interagency HIV Study underwent transthoracic echocardiography. There were 454 HIV-infected and 200 uninfected women, mean age 40.8 +/- 9.3 years. LV mass/height(2.7) was similar between the HIV-infected and the HIV-uninfected groups (41.4 +/- 11.1 vs. 39.9 +/- 10.3 g/h(2.7); p = 0.37). The prevalence of LVH was similar between the two groups (LVH by LV mass/height(2.7) criteria 15.0% vs. 13.0%, p = 0.29). Relative wall thickness (RWT), defined as the ratio of LV wall thickness to cavity diameter, was also similar between the HIV-infected and HIV-uninfected groups (0.36 +/- 0.05 vs. 0.37 +/- 0.06, p = 0.16). On multiple linear regression analysis adjusting for age, W/H ratio, triceps skinfold thickness, systolic/diastolic BP, diabetes, hypertension and dyslipidemia; HIV status (b = 2.08, p = 0.02, CI 0.27-3.88); weight (b per kg = 0.15, p < 0.01, CI 0.08-0.22); and smoking duration (b per one-year increase = 0.08, p = 0.03, CI 0.01-0.16) were independent correlates of LV mass/height(2.7) (Model R(2) = 0.20, p < 0.001). Weight (aOR = 1.04, CI 1.01-1.06) and smoking duration (aOR = 1.03, CI 1.01-1.06) were independent correlates of LVH. Being HIV negative, increased age, increased triceps skinfold thickness, and higher W/H ratio were independent correlates of higher RWT. Among HIV-infected women, higher LV mass was not associated with a history of AIDS-defining illness, nadir CD4(+) count <200 cells/microl, or with the duration of highly active antiretroviral therapy (HAART). Women taking NRTIs had higher LV mass. Higher RWT was associated with current CD4(+) count. In conclusion, HIV infection is associated with greater LV mass but not with a higher prevalence of LVH. Among HIV-infected women, RWT, but not LV mass, is associated with the degree of immunosuppression.

Risk Factors for Nevirapine-Associated Rash Among HIV-Infected Patients with Low CD4 Cell Counts in Resource-Limited Settings

Nevirapine (NVP) is commonly used as a component of first-line antiretroviral therapy in resource-limited countries. We aimed to determine the risk factors for NVP-associated rash among HIV-infected patients who were initiated NVP at low CD4 cell counts in a resource-limited setting. A case-control study was conducted in HIV-infected patients who developed rash after taking NVP (case) and those who did not have rash (control). A total of 357 patients with a mean (SD) age of 36.4 (7.5) years and 52.1% male were included in the study. Mean body weight (SD) was 55.5 (10.5) kg. Of all, 179 (49.0%) patients had a history of AIDS-defining illness and 57 (16.0%) patients had history of drug allergy. Median (IQR) CD4 cell counts at the time of NVP initiation was 95 (31-226) cells/mm(3). There were 115 patients in case group and 242 patients in control group. In case group, 43.0%, 54.4%, and 2.6% of patients developed grade 2, 3, and 4 of rash, respectively. Median time to develop rash was 12 (95%CI, 10.5-13.5) days. By logistic regression, history of drug allergy (OR, 3.41; 95%CI, 1.79-6.52), body weight (OR, 1.22 per each 5 kg decrement; 95%CI, 1.08-1.38), CD4 cells counts (OR, 1.20 per each 50 cells/mm(3) increment; 95%CI, 1.12-1.30), and AIDS-defining illness (OR, 0.42; 95%CI, 0.25-0.70) were significantly associated with rash. In resource-limited settings where patients were initiated NVP at low CD4 cell counts, history of drug allergy, lower body weight, and higher CD4 cell count are the risk factors for NVP-associated rash. Initiation of NVP in patients with these risks needs closed monitoring.

Central activation, muscle performance, and physical function in men infected with human immunodeficiency virus.

Loss of muscle mass and limitations in activity have been reported in persons infected with human immunodeficiency virus (HIV), even those who are otherwise asymptomatic. The extent to which factors other than muscle atrophy impair muscle performance has not been addressed in depth. The purpose of this study was to determine the extent of neuromuscular activation of the knee extensors and ankle dorsiflexors of 27 men infected with HIV receiving antiretroviral therapy and its relationship to muscle performance. The central activation ratio (CAR) was determined using superimposed electrical stimulation during maximum voluntary contractions. In addition to force and power measurements, muscle cross-sectional area and composition was evaluated using computed tomography. Aerobic capacity was determined from treadmill exercise testing. Eleven of the subjects had an impaired ability to activate the knee extensors (CAR = 0.72 +/- 0.12) that was associated with weakness and decreased specific force. The reduced central activation was not associated with muscle area, body composition, aerobic capacity, CD4 count, or medication regimen. Those individuals with low central activation had higher HIV-1 viral loads and were more likely to have a history of AIDS-defining illness. These results suggest the possibility of a different mechanism contributing to muscle impairment in the current treatment era that is associated with impairment of central motor function rather than atrophy. Further investigation is warranted in a larger, more diverse population before more definitive claims are made.

Gender and long‐term metabolic toxicities from antiretroviral therapy in HIV‐1 infected persons

Gender differences in a large population-based cohort of HIV-1 infected patients (245 women and 723 men) were examined with respect to the incidence of metabolic and morphologic alterations after initiation of highly active antiretroviral therapy (HAART). Patients initiated HAART between January 1996 and December 2003. The outcome measures were the incidence of hyperglycemia, hypercholesterolemia, symptomatic lactic acidosis, treatment-limiting lipodystrophy, and hypersensitivity reaction. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios of reaching the endpoints for exposures and covariates. Women were younger than men (35 +/- 9.8 vs. 40 +/- 8.2 years, P < 0.001) and more frequently from Haiti or Africa (59%), whereas 76% of men were Canadian-born. Type of initial HAART regimen did not differ between women and men. There were no gender differences in the overall incidence of hyperglycemia, hypercholesterolemia, or treatment-limiting lipodystrophy, even after adjusting for age, CD4 cell count, viral load, time since HIV diagnosis, history of AIDS-defining illness and year of HAART initiation. In contrast, women had significantly higher risk of developing lactic acidosis than men (P = 0.0009). Hypersensitivity reactions were also more frequent in women than men (adjusted hazard ratio = 4.4 (95% CI: 2.1-9.3)). Collectively, these data suggest that metabolic toxicities after HAART do not differ by gender but that lactic acidosis and hypersensitivity reactions are more frequent in women than men.

Evaluation of Subcutaneous Proleukin (Interleukin-2) in a Randomized International Trial (ESPRIT): Geographical and Gender Differences in the Baseline Characteristics of Participants

Background: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells ≥300 cells/μL. Objectives: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. Method: Baseline characteristics of randomized participants were summarized by region. Results: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/μL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). Conclusion: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability.