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Treatment of human immunodeficiency virus (HIV) infection with highly active combination antiretroviral therapy has increased survival and shifted the spectrum of HIV-associated morbidity and mortality from opportunistic infections toward a variety of other medical conditions. The prospective cohort Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) monitors the clinical course of HIV-infected individuals treated with combination antiretroviral therapy in 4 US cities. Every 6 months, clinical assessments, medical record abstraction, audio computer-assisted self-interview, and neurocognitive measurements are completed and blood and urine specimens are banked centrally. At enrollment and periodically thereafter, additional techniques such as anal cytology, dual energy x-ray absorptiometry, carotid ultrasonography, echocardiography, and abdominal and cardiac computed tomography are performed. From March 2004 through June 2006, 700 participants were enrolled; median age was 41 years, 76% were men, 58% were non-Hispanic white, 62% were men who have sex with men, 78% were taking combination antiretroviral therapy (of whom 86% had an HIV viral load of <400 copies/mL), and median CD4+ T-lymphocyte count was 459 cells/mm(3) (interquartile range: 324-660). The SUN Study provides a wealth of data that will inform and improve the clinical management of HIV-infected individuals in the modern era. [ABSTRACT FROM AUTHOR]

In the United States, transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) from health care exposures has been considered uncommon. However, a review of outbreak information revealed 33 outbreaks in nonhospital health care settings in the past decade: 12 in outpatient clinics, 6 in hemodialysis centers, and 15 in long-term care facilities, resulting in 448 persons acquiring HBV or HCV infection. In each setting, the putative mechanism of infection was patient-to-patient transmission through failure of health care personnel to adhere to fundamental principles of infection control and aseptic technique (for example, reuse of syringes or lancing devices). Difficult to detect and investigate, these recognized outbreaks indicate a wider and growing problem as health care is increasingly provided in outpatient settings in which infection control training and oversight may be inadequate. A comprehensive approach involving better viral hepatitis surveillance and case investigation, health care provider education and training, professional oversight, licensing, and public awareness is needed to ensure that patients are always afforded basic levels of protection against viral hepatitis transmission. [ABSTRACT FROM AUTHOR]

Background: Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population.Objective: To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003.Design: Prospective observational cohort studies.Setting: United States.Patients: 54,780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47,832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157,819 person-years of follow-up from 1992 to 2003, and 334,802,121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries.Measurements: Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population.Results: The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time.Limitations: Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated.Conclusion: The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003. [ABSTRACT FROM AUTHOR]

The syphilis epidemic among men who have sex with men (MSM) in major US cities and concomitant increases in high-risk sexual behavior, have raised concerns of increased HIV transmission in this population. Therefore, to provide information for health promotion and disease awareness efforts, we investigated sexual behaviors, partner selection preferences and HIV serostatus disclosure practices of MSM at the White Party in Palm Springs, California. Circuit party attendees reported engaging in unprotected anal sex, however, a high proportion reported disclosing their HIV status. These findings suggest that some gay men are serosorting as a risk reduction strategy or implementing sexual risk reduction strategies to protect themselves and their partners. In our study, HIV-negative men were nine times more likely to report a preference for a seroconcordant sexual partner. The self-protecting attitudes of HIV-negative men in our sample outweighed the partner-protecting attitudes of HIV-positive men. This suggests that prevention interventions focusing on HIV-positive persons are warranted. [ABSTRACT FROM AUTHOR]

Objectives Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). Methods We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n=165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF–) group; n=90], and who had normal baseline phosphate and creatinine values. Results The TDF+and TDF−groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P=0.18) and number of phosphate measurements (median=3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF−patients developed grade 2 hypophosphataemia (2.0–2.4 mg/dL), and 2.4% of TDF+patients vs 0% of TDF−patients developed grade 3 hypophosphataemia (1.0–1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+patients vs 8.0 per 100 person-years among TDF−patients ( P=0.11). Conclusions The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia. [ABSTRACT FROM AUTHOR]

Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum concentrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100-250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [OR(unadj)] 3.0, 95% confidence interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens (OR(unadj) 3.57; 95% CI, 0.72-24.1; p = 0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens (OR(adj) and 95% CIs undefined; p = 0.08). Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event--discontinuation for toxicity, treatment- emergent adverse event or abnormal laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI versus 13 (12%) of 105 on low-dose ddI developed any event (OR(unadj) 2.81; 95% CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was more frequently associated with drug-related toxicity, adverse events, and treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF was generally well tolerated in these HIV-infected persons. [ABSTRACT FROM AUTHOR]

To study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients.We estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV-infected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted.Of a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person–years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P=0.0008). PI exposure≥60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HRadj) 1.71; 95% confidence interval (CI) 1.08–2.74;P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HRadj 1.90; 95% CI 1.13–3.20;P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD.Patients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: Optimal timing of antiretroviral therapy (ART) initiation for HIV-infected persons remains unclear.Objective: To assess survival benefit of initiating ART at different CD4+ cell counts.Design: Prospective observational study.Setting: U.S. clinics in the HIV Outpatient Study (HOPS).Patients: HIV-infected patients with CD4+ cell counts, plasma HIV RNA viral load, and ART use recorded from January 1994 through March 2002.Measurements: Before initiation of ART, patients were grouped by their CD4+ cell counts into three subgroups: 0.201 to 0.350 x 10(9) cells/L (n = 399), 0.351 to 0.500 x 10(9) cells/L (n = 327), and 0.501 to 0.750 x 10(9) cells/L (n = 122). We compared mortality rates for each CD4+ subgroup among patients who initiated ART and patients who delayed ART until reaching a lower CD4+ subgroup.Results: Mortality rates for 340 patients who initiated ART and 59 who delayed ART in the CD4+ subgroup of 0.201 to 0.350 x 10(9) cells/L were 15.4 and 56.4 deaths per 1000 person-years, respectively (rate ratio, 0.27 [95% CI, 0.14 to 0.55]; P < 0.001). For the CD4+ subgroup of 0.351 to 0.500 x 10(9) cells/L, mortality rates for 240 patients who initiated ART and 887 who delayed ART were 10.0 and 16.6 deaths per 1000 person-years, respectively (rate ratio, 0.61 [CI, 0.22 to 1.67]; P = 0.17). For the CD4+ subgroup of 0.501 to 0.750 x 10(9) cells/L, mortality rates in 55 patients who initiated ART and 67 who delayed ART were 7.5 and 3.1 deaths per 1000 person-years, respectively (rate ratio, 1.20 [CI, 0.17 to 8.53]; P > 0.2). Patients in the 0.201 to 0.350 x 10(9) cells/L and 0.351 to 0.500 x 10(9) cells/L CD4+ subgroups who initiated ART were more likely than those who delayed ART to achieve an undetectable HIV viral load (P = 0.03 and 0.04, respectively).Conclusions: Among HIV-infected persons with CD4+ cell counts of 0.201 to 0.350 x 10(9) cells/L, initiating ART is associated with reduced mortality compared with delaying such therapy. Survival benefits of earlier ART initiation (at CD4+ cell counts of 0.351 to 0.500 x 10(9) cells/L) are possible. [ABSTRACT FROM AUTHOR]

Context: During the past decade, knowledge of human immunodeficiency virus (HIV) infection in women has expanded considerably but may not be easily accessible for use in understanding and prioritizing the clinical needs of HIV-infected women.Objectives: To perform a comprehensive review of epidemiologic, clinical, psychosocial, and behavioral information about HIV in women, and to recommend an agenda for future activities.Data Sources: A computerized search, using MEDLINE and AIDSline, of published literature was conducted; journal articles from January 1981 through July 2000 and scientific conference presentations from January 1999 through July 2000 were retrieved and reviewed for content; article reference lists were used to identify additional articles and presentations of interest.Study Selection: Data from surveillance and prospective cohort studies with at least 20 HIV-infected women and appropriate comparison groups were preferentially included.Data Extraction: Included studies of historical importance and subsequent refined analyses of topics covered therein; these and studies with more current data were given preference. Four studies involving fewer than 20 women were included; 2 studies were of men only.Data Synthesis: Women account for an increasing percentage of all acquired immunodeficiency syndrome (AIDS) cases, from 6.7% (1819/27 140 cases) in 1986 to 18% (119 810/724 656 cases) in 1999. By the end of 1998, of all newly reported AIDS cases among women, proportionally more were in the South (41%), among black women (61%), and from heterosexual transmission (38%). Of note, increasingly more women have no identified or reported risk, about half or more of whom are estimated to be infected heterosexually. It is estimated that a total of at least 54% of women newly reported with AIDS in 1998 acquired HIV through heterosexual sex, including women in the no identified or reported risk category estimated to have been infected heterosexually, meeting the surveillance heterosexual risk definition. Natural history, progression, survival, and HIV-associated illnesses-except for those of the reproductive tract-thus far appear to be similar in HIV-infected women and men. Although antiretroviral therapy has proven to be highly effective in improving HIV-related morbidity and mortality rates, women may be less likely than men to use these therapies. Drug use, high-risk sex behaviors, depression, and unmet social needs interfere with women's use of available HIV prevention and treatment resources.Conclusions: Continued research on HIV pathogenesis and treatment is needed; however, emphasis should also be placed on using existing knowledge to improve the clinical care of women by enhancing use of available services and including greater use of antiretroviral therapy options, treating depression and drug use, facilitating educational efforts, and providing social support for HIV-infected women. [ABSTRACT FROM AUTHOR]

Health care needs of those infected with the human immunodeficiency virus (HIV) and subsequent transmission dynamics are altered by migration after infection. We interviewed 760 HIV-infected persons attending HIV-specialty clinics living in non-urban Alabama and Mississippi to ascertain the likely geographic origins of their infections, determine their post-HIV diagnosis mobility, and identify predictors of this mobility. Most subjects (81%) were living in these two states when diagnosed and have not moved since learning of their HIV status (70%). Of those who moved their primary residence post-HIV diagnosis (25% of the entire study population), the majority in-migrated to Alabama or Mississippi from elsewhere. Persons who had moved post-HIV diagnosis were more likely to be male, an injection drug user, an urban resident at HIV diagnosis, have an AIDS-defining condition, and have moved prior to HIV diagnosis. We conclude that most HIV transmission in non-urban Alabama and Mississippi is acquired locally. These results underline the need to expand HIV prevention programs in the Deep South. [ABSTRACT FROM AUTHOR]

Health care needs of those infected with the human immunodeficiency virus (HIV) and subsequent transmission dynamics are altered by migration after infection. We interviewed 760 HIV-infected persons attending HIV-specialty clinics living in non-urban Alabama and Mississippi to ascertain the likely geographic origins of their infections, determine their post-HIV diagnosis mobility, and identify predictors of this mobility. Most subjects (81%) were living in these two states when diagnosed and have not moved since learning of their HIV status (70%). Of those who moved their primary residence post-HIV diagnosis (25% of the entire study population), the majority in-migrated to Alabama or Mississippi from elsewhere. Persons who had moved post-HIV diagnosis were more likely to be male, an injection drug user, an urban resident at HIV diagnosis, have an AIDS-defining condition, and have moved prior to HIV diagnosis. We conclude that most HIV transmission in non-urban Alabama and Mississippi is acquired locally. These results underline the need to expand HIV prevention programs in the Deep South. [ABSTRACT FROM AUTHOR]