Showing papers in "Journal of Acquired Immune Deficiency Syndromes in 2003"

Coronary heart disease in HIV-infected individuals.

Abstract: It is currently unknown whether there is an increased risk of coronary heart disease (CHD) in patients with HIV infection. In addition, the contribution of antiretroviral therapy (ART) to CHD risk has not been quantified. We reviewed administrative claims data for HIV-infected and -uninfected individuals from the California Medicaid population and compared the incidence of and relative risk (RR) for CHD using log-linear regression analyses between groups. The association between exposure to ART and CHD incidence was also assessed. Of 3,083,209 individuals analyzed, 28,513 were HIV-infected. The incidence of CHD among young men (up to age 34) and women (up to age 44) with HIV infection was significantly higher than that among non-HIV-infected individuals. The covariate-adjusted RR for the development of CHD in individuals receiving ART compared with those not receiving ART was 2.06 (P < 0.001) in HIV-infected individuals aged 18-33 years. There were no statistically significant associations between ART exposure and CHD in other age groups. CHD incidence appears accelerated among young HIV-infected individuals. Strategies to reduce CHD risk should be incorporated into HIV primary care.

Barriers to antiretroviral adherence for patients living with HIV infection and AIDS in Botswana.

Abstract: Background: Botswana has the highest rate of HIV infection in the world estimated at 36% among the population aged 15–49 years. To improve antiretroviral (ARV) treatment delivery we conducted a cross-sectional study of the social cultural and structural determinants of treatment adherence. Methods: We used both qualitative and quantitative research methodologies including questionnaires and interviews with patients receiving ARV treatment and their health care providers to elicit principal barriers to adherence. Patient report and provider estimate of adherence (>/95% doses) were the primary outcomes. Results: One hundred nine patients and 60 health care providers were interviewed between January and July 2000; 54% of patients were adherent by self-report while 56% were adherent by provider assessment. Observed agreement between patients and providers was 68%. Principal barriers to adherence included financial constraints (44%) stigma (15%) travel/migration (10%) and side effects (9%). On the basis of logistic regression if cost were removed as a barrier adherence is predicted to increase from 54% to 74%. Conclusions: ARV adherence rates in this study were comparable with those seen in developed countries. As elsewhere health care providers in Botswana were often unable to identify which patients adhere ad-here to their ARV regimens. The cost of ARV therapy was the most significant barrier to adherence. (authors)

Age differences in sexual partners and risk of HIV-1 infection in rural Uganda.

Abstract: Objectives: To assess whether differences in age between sexual partners affect the risk of HIV infection in female adolescents and young adults. Methods: A total of 6177 ever sexually active women aged 15 to 29 years completed a sociodemographic and sexual behavior questionnaire and provided a blood sample for HIV-1 serology. The age difference between partners was categorized as men 0 to 4 years older (referent group) 5 to 9 years older and 10 or more years older. HIV prevalence and incidence were assessed and adjusted RR was estimated by multivariate regression. Results: Prevalent HIV-1 infection in female participants increased with older male sexual partners. Among women aged 15 to 19 years the adjusted risk of HIV infection doubled (RR = 2.04; 95% CI: 1.29–3.22) among those reporting male partners 10 or more years older compared with those with male partners 0 to 4 years older; among women 20 to 24 years of age the RR was 1.24 (95% CI: 0.96–1.60). The attributable fraction (exposed) of prevalent HIV infection in women aged 15 to 24 years associated with partners 10 or more years older was 9.7% (95% CI: 5.2–14.0). HIV incidence did not increase with differences in age of partners. Conclusion: The age difference between young women and their male partners is a significant HIV risk factor suggesting that high HIV prevalence in younger women is caused in part by transmission from older male partners. (authors)

A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients.

Abstract: All classes of antiretroviral (ARV) therapy have been associated with asymptomatic elevations of alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels, and much less frequently with serious, and at times life threatening, clinical liver hepatotoxicity. The relationship between the risk of developing serious clinical liver injury and the rate and severity of elevated asymptomatic ALT/AST levels is poorly understood. Boehringer Ingelheim has recently completed the Viramune® Hepatic Safety Project; its primary objective was to identify risk factors for antiretroviral-associated hepatotoxicity. Data from 1731 nevirapine-treated patients and 1912 control patients who took part in Boehringer Ingelheim-controlled clinical trials as well as 814 nevirapine-treated patients in uncontrolled trials were analyzed. Risk factors for asymptomatic ALT/AST elevations during nevirapine therapy included baseline elevations of ALT/AST levels >2.5x upper limit of normal (RR = 4.3, p 5× ULN for patients stratified by baseline CD4 cell count demonstrated that men with ≥400 CD4 cells/mm 3 were at increased risk of asymptomatic transaminase elevations while taking nevirapine (RR = 1.6, p <.01). No consistent CD4 cell count cutoff could be identified in women that was associated with an increased risk of ALT/AST elevations. Analyses from five large observational cohorts (N = 8711) demonstrated no significant differences in the rate of serious hepatic events among antiretroviral regimens, including between the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Use of nevirapine was not associated with a significantly increased risk of clinical hepatotoxic events, including liver failure or liver related death, compared to therapy with other antiretroviral drugs.

Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort.

Abstract: Objectives To describe the patterns and correlates of discontinuation of the initial highly active antiretroviral therapy (HAART) regimen in an urban, outpatient cohort of antiretroviral-naive patients. Design Retrospective cohort of 345 randomly selected antiretroviral-naive patients who initiated HAART on 6 selected regimens between January 1997 and May 2001 in New Orleans, LA. Methods An investigator reviewed medical records to collect information on concurrent medications, symptoms/diagnoses, staging indicators, and reasons for HAART discontinuation. Proportional hazards regression methods were used to identify predictors of discontinuation. Results After a median follow-up of 8.1 months, 61% of patients changed or discontinued their initial HAART regimen; 24% did so because of an adverse event. The events most commonly cited as the cause for discontinuation were nausea, vomiting, and diarrhea. A detectable viral load was associated with discontinuation at any time, while reporting nausea/vomiting or dizziness at the previous visit were associated with discontinuation during the first 3 months on HAART. Nausea/vomiting and not having AIDS at the time of HAART initiation were associated with discontinuation due to an adverse event at any time, while a high viral load, and dizziness or anorexia/weight loss at the previous visit were associated with discontinuation due to an adverse event in the first 3 months on HAART. Conclusions Gastrointestinal adverse events of HAART are the most frequently cited reason for discontinuation of HAART. An effort should be made to educate patients about these events and to encourage continued adherence. Additionally, appropriate prophylaxes for these events are warranted.

Immune deficiency and risk for malignancy among persons with AIDS.

Abstract: Background: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset. Methods: We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm 3 , 50-99 cells/mm 3 , 100-199 cells/mm 3 , and ≥200 cells/mm 3 ) was modeled using Poisson regression. Results: The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm 3 , RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR = 1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm 3 ) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p =.74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts. Conclusions: KS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.

Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects.

Abstract: Three dose levels of the protease inhibitor (PI) atazanavir (200, 400, and 500 mg once daily) were compared with nelfinavir (750 mg three times daily) when given both as monotherapy and in combination with didanosine and stavudine in 420 antiretroviral-naive subjects infected with HIV-1. Subjects received monotherapy for 2 weeks, followed by combination therapy for 46 weeks. After 48 weeks, mean change from baseline in HIV RNA (-2.57 to -2.33 log 10 copies/mL), the proportion of subjects with HIV RNA <400 copies/mL (56%-64%) and <50 copies/mL (28%-42%), and mean increases in CD4 cell count (185-221 cells/mm 3) were comparable across treatment groups. Diarrhea was two to three times more common in the nelfinavir group (61% of subjects) than in the atazanavir groups (23%-30% of subjects, <.0001 versus nelfinavir), and jaundice occurred only in atazanavir-treated subjects (6%, 6%, and 12% in the 200-, 400-, and 500-mg groups, respectively) ( <.03 for all atazanavir regimens vs. nelfinavir). Mean percent change from baseline in fasting low-density lipoprotein (LDL) cholesterol was significantly less in the atazanavir groups (-7% to 4%) than in the nelfinavir group (31%) ( <.0001). In conclusion, once-daily atazanavir is a potent, safe, and well tolerated PI that rapidly and durably suppresses HIV RNA and durably increases CD4 cell count in antiretroviral-naive subjects. Through 48 weeks, atazanavir was not associated with clinically relevant increases in total cholesterol, fasting LDL cholesterol, or fasting triglycerides. In comparison, nelfinavir was associated with prompt, marked, and sustained elevations in these parameters of a magnitude that suggests they are clinically relevant.

HTLV-I in the general population of Salvador, Brazil: a city with African ethnic and sociodemographic characteristics.

Abstract: The city of Salvador has the highest prevalence of HTLV-I among blood donors in Brazil. To study the prevalence of HTLV-I among the general population of Salvador, 30 "sentinel surveillance areas" were selected for the investigation of various infectious diseases, and 1385 individuals within these areas were surveyed according to a simple random sample procedure. ELISA was used to screen plasma samples for antibodies to HTLV-I, and the positive samples were tested by a confirmatory assay (Western blotting). The overall prevalence of HTLV-I was 1.76% (23/1385). Infection rates were 1.2% for males and 2.0% for females. Specific prevalence demonstrated an increasing linear trend with age. No one younger than 13 years of age was infected. Multivariate analysis estimated adjusted odds ratios for the association of HTLV-I with age of 9.7 (3.3; 30.4) for females and 12.3 (1.47; 103.1) for males. Less education and income might be associated with HTLV-I infection in females. Phylogenetic analysis of the long terminal repeat fragments showed that most of the samples belonged to the Latin American cluster of the Transcontinental subgroup (Cosmopolitan subtype). For the entire city of Salvador, it is estimated that approximately 40000 individuals are infected with HTLV-I. Our results suggest multiple post-Colombian introductions of African HTLV-Ia strains in Salvador.

Overcoming barriers to HIV testing: Preferences for new strategies among clients of a needle exchange, a sexually transmitted disease clinic, and sex venues for men who have sex with men

Abstract: Objective: To determine strategies to overcome barriers to HIV testing among persons at risk. Methods: We developed a survey that elicited testing motivators, barrier, and preferences for new strategies among 460 participants at a needle exchange, three sex venues for men who have sex with men, and a sexually transmitted disease clinic. Results: Barriers to testing included factors influenced by individual concern (fear and discrimination); by programs, policies, and laws (named reporting and inability to afford treatment); and by counseling and testing strategies (dislike of counseling, anxiety waiting for results, and venipuncture). The largest proportions of participants preferred rapid testing strategies, including clinic-based testing (27%) and home self-testing (20%); roughly equal proportions preferred oral fluid testing (18%), urine testing (17%), and standard blood testing (17%). One percent preferred home specimen collection. Participants who had never tested before were significantly more likely to prefer home self-testing compared with other strategies. Blacks were significantly more likely to prefer urine testing. Conclusions: Strategies for improving acceptance of HIV counseling and testing include information about access to anonymous testing and early treatment. Expanding options for rapid testing, urine testing, and home self-testing; providing alternatives to venipuncture; making pretest counseling optional; and allowing telephone results disclosure may encourage more persons to learn their HIV status.

Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women

Abstract: Objective To assess the association between protease inhibitor (PI) use and the incidence of diabetes mellitus (DM) among participants in the Women's Interagency HIV Study. Design Prospective multicenter cohort study. The diagnosis of DM was based on self-report at semiannual interviews conducted from 1994 to 1998. Setting Six inner-city clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA). Participants A total of 1785 nonpregnant women who had no history of prior DM. The women made up four groups: 1) PI users (n = 609, person-years [PY] at risk = 707); 2) reverse transcriptase inhibitor (RTI)-only users (n = 932, PY = 1486); 3) HIV-infected women reporting no antiretroviral therapy (ART) ever (n = 816, PY = 1480); and 4) HIV-uninfected women (n = 350, PY = 905). Main outcomes Incidence of DM and median body mass index (BMI) from 1995 to 1998 were compared among the four groups. Results Sixty-nine incident cases of DM occurred among 1785 women (1.5 cases per 100 PY; 95% CI: 1.2-1.9). The incidence of DM among PI users was 2.8 cases per 100 PY (2.8%) versus 1.2% among both RTI users and women on no ART (95% CI: 1.6-4.1 [PI]; 0.7-1.8 [RTI and no ART]; P = 0.01 for comparison of the PI group with the RTI group) and 1.4% among HIV-uninfected women (95% CI: 0.7-2.2, P = 0.06 for comparison with PI group). Weight gain was not associated with either PI or RTI use. Multivariate models identified PI use (hazard ratio [HR] = 2.90 [95% CI: 1.50-5.60]; P = 0.002), age (HR = 1.75 per 10 years [95% CI: 1.31-2.34]; P = 0.0002) and BMI as independent risk factors for DM. Conclusions PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.

Exposure to antiretroviral therapy in utero or early life: The health of uninfected children born to HIV-infected women

Abstract: Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life (p

Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients.

Abstract: To identify clinical factors associated with the incidence of HIV-1-associated lipoatrophy, HIV-1-infected patients in the HIV Outpatient Study (HOPS) were prospectively evaluated for clinical signs of lipoatrophy at two visits about 21 months apart. Development of lipoatrophy was analyzed in stratified and multivariate analyses for its relationship to immunologic, virologic, clinical, and drug treatment information for each patient. Of 337 patients with no lipoatrophy at Survey 1, 44 (13.1%) developed moderate or severe lipoatrophy between the two surveys. In multivariate analyses, significant risk factors for incident lipoatrophy were white race (OR = 5.2; 95% CI: 1.9-17.1; p =.003), CD4 T-lymphocyte count at Survey 2 less than 100 cells/mm 3 (OR = 4.2; 95% CI: 1.3-13.1; p =.013), and body mass index (BMI) less than 24 kg/m 2 (OR = 2.4; 95% CI: 1.1-5.4; p =.024). Analyses that controlled for the severity of HIV illness demonstrated no significant association with use of or time on any antiretroviral agent or class of agents and the development of lipoatrophy. Some host factors and factors associated with previous or current severity of HIV infection, especially CD4 T-lymphocyte cell count, appeared to have the strongest association with incidence of lipoatrophy.

Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers.

Abstract: Although children born to HIV-infected (HIV+) women receiving antiretroviral therapy during pregnancy show virtually no adverse clinical effects at birth, the antiretroviral nucleoside analog drugs are known to damage nuclear and mitochondrial DNA. In this study, biomarkers of mitochondrial toxicity and genotoxicity have been examined in a well-characterized sample set consisting of infants born to HIV-uninfected (HIV-) mothers (n = 30), and HIV- infants (n = 20) born to HIV-infected (HIV+) mothers who received either no antiretroviral therapy (n = 10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) during pregnancy (n = 10). DNA from cord blood leukocytes and peripheral blood leukocytes taken at 1 and 2 years of age was examined for loss of mitochondrial DNA (mtDNA) and telomere integrity. Telomere length, a measure of nuclear DNA damage, was the same in all infants at birth and at age 1 year. The quantity of mtDNA was assessed relative to nuclear DNA using a polymerase chain reaction-based chemiluminescence detection (PCR-CID) method that determined mitochondrial D Loop gene copies relative to nuclear 18S RNA gene copies by comparison with a standard curve. MtDNA quantity was expressed as a ratio of gene copy numbers. In infants of uninfected mothers (AZT-/HIV-) at the three time points, the ratios were 442 to 515, whereas in infants of untreated AZT-/HIV+ mothers the ratios were 261 to 297, and in infants of AZT-treated (AZT+/HIV+) mothers the ratios were 146 to 203. At all three time points, differences between the AZT-/HIV- group and the two HIV+ groups were statistically significant (p <.05), and differences between the AZT-/HIV+ and AZT+/HIV+ groups were also statistically significant (p <.05), demonstrating that AZT exposure causes a persistent depletion of mtDNA. The study shows that children of HIV+ mothers are at risk for mitochondrial damage that is further increased in infants of mothers receiving AZT during pregnancy.

Review of medical encounters in the 5 years before a diagnosis of HIV-1 infection: implications for early detection.

Abstract: Early detection of HIV infection improves prognosis and reduces transmission, but 30%-40% of cases are diagnosed late. A comprehensive and systematic review of medical encounters before diagnosis has not been done. This study reviews 5 years of medical encounters before the diagnosis of HIV infection in members of a large managed care organization where access to care is reasonably good. Patient characteristics, HIV risk factors, and clinical events preceding diagnosis were examined and tested for association with late diagnosis (CD4 cell count of 1 year before diagnosis. Only 22% of patients had one of eight clinical indicators suggested in the literature as reasons to test for HIV >1 year before diagnosis. In multiple logistic regression, older age, male sex, race, risk group, no prior HIV testing, physician-initiated testing, and having any of eight clinical indicators before diagnosis were each associated with late diagnosis (p

AIDS and older Americans at the end of the Twentieth Century.

Abstract: In the past 11 years, the cumulative number of AIDS cases reported to the Centers for Disease Control and Prevention in adults aged 50 years or older quintupled, from 16,288 in 1990 to 90,513 by the end of December 2001. This article provides an overview of AIDS cases through 2001, shows the growing totals of AIDS cases among persons aged 50 years or older, and describes and compares these cases with those among younger people. It also reviews work on perceptions of persons aged 50 years or older on their risk for contracting HIV and their preventive health practices. Most of the data for this article came from the CDC web site and the AIDS public use data set. Although the incidence of AIDS appears to be leveling off in the general population, the data show that older people as a group represent a substantial share of new cases. There are currently more than 60,000 persons estimated to be aged 50 years or older living with AIDS in the United States; more than 50,000 persons with AIDS in this age group have died since the epidemic began. In light of the new era of highly active antiretroviral therapy, it can be expected that the AIDS epidemic will continue to age in multifaceted ways.

Assessment of adherence to antiviral therapy in HIV-infected children using the Medication Event Monitoring System, pharmacy refill, provider assessment, caregiver self-report, and appointment keeping.

Abstract: The authors sought to assess the utility of the electronic Medication Event Monitoring System (MEMS) in monitoring adherence to highly active antiretroviral therapy (HAART) in HIV-infected children and to compare this with other methods of adherence assessment. Twenty-six perinatally HIV-infected children being treated with three or more antiretroviral medications and their caregivers were enrolled and prospectively followed-up for 6 months. Adherence was assessed using MEMS monitoring of one antiretroviral, pharmacy refill records of all antiretrovirals, a caregiver self-report interview, a physician/nurse questionnaire, and appointment-keeping behavior. Viral loads measured at the end of the 6-month period were compared with the various adherence assessment methods. Adherence rates for the MEMS-monitored medication ranged from 12.7% to 97.9% (median = 81.4%), and 11 of the participants (42%) had less than 80% adherence using this method. A MEMS adherence rate greater than 80% was associated with viral load below the threshold of detection 6 months after enrollment (p <.001). Although not as robust, pharmacy refill rates for all antiretroviral medications were also associated with virologic response. The highest specificity was attained when both MEMS and pharmacy refill were used in combination. Physician assessment of adherence rate as well as appointment-keeping behavior was associated with virologic response, whereas caregiver self-report was not.

Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women

Abstract: Background: Data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited. Objective: To determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women. Design: The incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women. Setting: Women from the general community or HIV care clinics in four urban locations in the United States. Outcome Measures: Creatinine of ≥1.4 mg/dL, proteinuria 2 + or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%). Results: At baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9-3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2,7%), p <.0001) in HIV-infected women with, compared with those without these renal abnormalities. Conclusions: Proteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons.

Impact of a patient education program on adherence to HIV medication: a randomized clinical trial.

Abstract: Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.

Performance characteristics of a new less sensitive HIV-1 enzyme immunoassay for use in estimating HIV seroincidence.

Abstract: Less sensitive (LS) HIV-1 enzyme immunoassays (EIAs) have significantly improved the quantity and quality of HIV surveillance data. The first LS-HIV-1 EIA, the Abbott 3A11-LS, provided reliable incidence data, but the assay required specialized equipment, and the lack of available reagents made testing difficult. This study evaluated the use of an alternate assay, a modified version of the Vironostika HIV-1 EIA (Vironostika-LS), to be used for LS testing. The Vironostika-LS has similar performance characteristics to the Abbott 3A11-LS with additional advantages. This 96-well formatted assay is commonly found in public health laboratories for routine HIV-1 testing and can be used with both serum and dried blood spot specimens. The estimated mean time from seroconversion (defined using a standardized optical density cutoff of 1.0) with the Vironostika-LS was 170 days (95% CI, 145-200 days). When the Vironostika-LS was applied to a matched serum set previously tested with the Abbott 3A11-LS, the Vironostika-LS accurately identified 97% of specimens with recent or long-standing HIV infection. The paper also reports Vironostika-LS quality control guidelines and the results from 3 rounds of proficiency testing.

Virologic, immunologic, and clinical response to highly active antiretroviral therapy: the gender issue revisited.

Abstract: Background: Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis for patients with HIV. There is ongoing debate over a potential gender effect on patient outcome after HAART.Methods: Individuals were from the EuroSIDA cohort, naive to protease inhibitors and nonnucleoside reverse transcriptase inhibitors, and had at least one viral load and CD4 measurement prior to starting HAART. Endpoints were virologic (time to 500 copies/mL]), immunologic (time to a 100/mm cell rise in CD4 count) and clinical (time to new AIDS and death).Hazard ratios (HR), derived using Cox regression models, compared female to male rates of achieving endpoints.Results: Of 2547 patients, 20% (511) were female. Significantly more females than males were nonwhite (24% vs. 10%, p <.001). Males were older (median age 39 vs. 35 years, p <.0001), had lower CD4 counts (211 vs. 240/mm, p =.03), higher viral loads (4.6 vs. 4.4 log copies/mL, p <.0001), were more likely to have a history of AIDS (26% vs. 18%, p <.001) and were more likely to be treatment-naive (34% vs. 29%, p =.03). Adjusted HR for association between gender (comparing females with males) and the outcomes studied were as follows: for reaching <500 copies/mL 0.91 (0.81-1.03, p =.17), rebound 1.17 (0.95-1.44, p =.15), for 100 cell CD4 count rise 1.02 (0.88-1.14, p =.99), for progression to new AIDS 1.12 (0.73-1.71, p =.59) and for time to death 1.15 (0.69-1.92, p =.57).Conclusions: We found no significant evidence of a gender difference in virologic, immunologic, or clinical outcomes after starting HAART.

How harmful is hazardous alcohol use and abuse in HIV infection: do health care providers know who is at risk?

Abstract: We conducted a prospective cohort study to describe the association between alcohol use, HIV disease progression, and drug toxicity and to determine health care provider awareness of excessive alcohol use by recruiting 881 HIV-infected veterans (median age, 49 years; 99% male; 54% African American) from 3 VA HIV clinics. Twenty percent of patients were hazardous drinkers by the Alcohol Use Disorders Identification Test, 33% were binge drinkers, 32% had a chart ICD-9 alcohol diagnosis, and 12.5% and 66.7%, respectively, were described by their health care providers as currently and ever drinking "too much." Hazardous/binge drinkers more often had detectable viral loads (P 200/mL. We conclude that in HIV-positive veterans, hazardous drinking and alcohol diagnoses were common and associated with HIV disease progression and/or hepatic comorbidity and anemia. Health care providers more often missed alcohol problems in patients with less severe HIV infection and those without evidence of liver disease. Health care providers should routinely screen and counsel patients regarding alcohol problems as part of standard of care to minimize disease progression and bone marrow and hepatic toxicity.

Concurrent partnerships among rural African Americans with recently reported heterosexually transmitted HIV infection.

Abstract: Objectives To investigate concurrent sexual partnerships among African Americans in North Carolina with recently reported heterosexually transmitted HIV infection. Design Population-based case series of persons with newly reported HIV infection. Methods Household interviews concerning sexual and other risk behaviors for HIV transmission were conducted among African Americans, 18–59 years old, who had been reported to the state health department within the preceding 6 months as having heterosexually acquired HIV infection. Dates of sexual partnerships were analyzed to identify concurrency among the 3 most recent partnerships. Results Concurrency prevalence in the past 1 and 5 years, respectively, was 45 and 63% for men and 37 and 58% for women. Most respondents (87%) believed that a recent partner had had a concurrent partnership. Multivariate analysis revealed associations between concurrency and male gender, youth, crack cocaine smoking, and incarceration of a sex partner. Conclusions Concurrent partnerships likely accelerate heterosexual HIV transmission among blacks in the rural southeastern United States. Future research should examine the socioeconomic context that supports this network pattern.

Health-related quality of life after 1 year of highly active antiretroviral therapy.

Abstract: Objective: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health-related quality of life (HRQL). Methods: Medical data for patients in the French APROCO cohort were collected at enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey) and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a normal HRQL. Results: Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm 3 , time since HIV diagnosis <8 years, undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12. Conclusion: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long-term strategies properly and to optimize the durability of response to antiretroviral therapy.

Effect of Maternal HIV and Malaria Infection on Pregnancy and Perinatal Outcome in Zimbabwe

Abstract: Objective: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. Methods: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. Results: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7% respectively. HIV infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96 95% confidence interval (CI): 2.42–6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74 95% CI: 1.34–16.78) and preterm delivery (OR = 4.10 95% CI: 2.17–7.75) respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09 95% CI: 6.50–15.65; HIV: OR = 3.16 95% CI: 1.80–5.54) and very low birth weight (malaria: OR = 5.04 95% CI: 1.00–25.43; HIV: OR = 10.74 95% CI: 2.12– 54.41) low Apgar score (malaria: OR = 4.45 95% CI: 1.42–13.94; HIV: OR = 5.94 95% CI: 1.66–21.30) and fetal growth restriction (malaria: OR = 3.98 95% CI: 2.51–6.30; HIV: OR = 4.07 95% CI: 2.40–6.92). Dual infection with malaria and HIV was associated with increased risk of maternal perinatal and early infant death. Conclusions: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist. (authors)

Impaired virologic response to highly active antiretroviral therapy associated with ongoing injection drug use.

Abstract: Injection drug users who continue to use drugs may not respond to highly active antiretroviral therapy (HAART) as well as other HIV-infected individuals, even after adjusting for a reliable measure of adherence. We therefore compared the virologic response among participants in a population-based HIV/AIDS Drug Treatment Program in British Columbia, Canada, by injection drug use activity. Participants who were HIV infected and naive to antiretroviral therapy and who were prescribed antiretroviral treatment between August 1996 and December 2000 were eligible for this study. They were classified as current, former, or non-injection drug users. The main outcome was having two consecutive HIV-1 RNA levels less than 500 copies/mL. We used logistic regression to adjust for baseline HIV-1 RNA, type of antiretroviral regimen (2 nucleosides + nonnucleoside reverse transcriptase inhibitor versus 2 nucleosides + protease inhibitor), duration of therapy (months), adherence (derived from refill compliance data), and age. A total of 578 participants were first prescribed HAART during the study period. Among them, 78 (13%) were current injection drug users, 96 (17%) were former injection drug users, and 404 (70%) never injected drugs. In the multivariable logistic regression, relative to non-drug users, current injection drug users were significantly less likely to suppress their HIV-1 RNA (adjusted OR [AOR] = 0.30, 95% CI: 0.13-0.67), and former injection drug users were not significantly different from non-drug users (AOR = 0.56, 95% CI: 0.24-1.34). There was a significant interaction between drug use and adherence. In the analyses stratified by drug use, the adherence of former and non-drug users was positively associated with HIV-1 RNA suppression (AOR = 1.33, 95% CI: 1.14-1.55), whereas for current drug users, it was not (AOR = 1.07, 95% CI: 0.87-1.33). Current injection drug users were less likely to achieve HIV-1 RNA suppression compared with non-drug users. Adherence as measured by pharmacy refill compliance was not a reliable measure in this subpopulation.

Grade 4 events are as important as AIDS events in the era of HAART.

Abstract: Objective To estimate incidence and predictors of serious or life-threatening events that are not AIDS defining, AIDS events, and death among patients treated with highly active antiretroviral therapy (HAART) in the setting of 5 large multicenter randomized treatment trials conducted in the United States. Methods Data were analyzed from 2,947 patients enrolled from December 1996 through December 2001. All patients were to receive antiretrovirals throughout follow-up. Data collection was uniform for all main outcome measures: serious or life-threatening (grade 4) events, AIDS, and death. Results During follow-up, 675 patients experienced a grade 4 event (11.4 per 100 person-years); 332 developed an AIDS event (5.6 per 100 person-years); and 272 died (4.6 per 100 person-years). The most common grade 4 events were liver related (148 patients, 2.6 per 100 person-years). Cardiovascular events were associated with the greatest risk of death (hazard ratio = 8.64; 95% CI: 5.1 to 14.5). The first grade 4 event and the first AIDS event were associated with similar risks of death, 5.68 and 6.95, respectively. Conclusions Grade 4 events are as important as AIDS events in the era of HAART. To adequately evaluate the impact of HAART on morbidity, comorbidities and other key factors must be carefully assessed.

Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover.

Abstract: To evaluate the relationship between T cell turnover, immune activation, and CD4 recovery in HIV infection, 32 antiretroviral-naive HIV-1-infected patients were studied before and after initiation of highly active antiretroviral therapy (HAART). Elevated CD4 and CD8 T cell turnover (measured by Ki67) in HIV infection decreased with HAART in blood and lymphoid tissue. Increased peripheral CD4 T cell turnover was strongly associated with immune activation even after viral suppression to less than 50 copies/mL (R = 0.8; p <.001). Increased CD4 T cell turnover correlated strongly with CD4 cell counts both before (R = -0.6; p <.001) and after (R = -0.4; p =.05) HAART. In patients with baseline CD4 cell counts of less than 350/microL, decreases in CD4 T cell turnover with HAART significantly correlated with increases in CD4 cell counts. In addition, persistently elevated levels of CD4 T cell turnover after HAART were associated with incomplete CD4 T cell recovery despite HIV RNA levels of less than 50 copies/mL. These data suggest that immune activation is central to CD4 cell depletion in HIV infection and immune reconstitution with HAART.

A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy

Abstract: Background: The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear. No treatment of lipoatrophy is currently established. Methods: This was an open-label randomized study of HIV-positive individuals on a first-line therapy containing stavudine (d4T) with either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180 mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients switched d4T to abacavir (ABC) (group I ), a PI or NNRTI to ABC (group 2), or d4T and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomography (CT) scans for 48 weeks. Results: Thirty patients were included, with 27 completing 48 weeks of therapy. One ABC hypersensitivity reaction was the only serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low-density lipoprotein cholesterol improved significantly in groups 2 and 3. Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3. Visceral adiposity (by CT scan) was unaffected in all groups. Conclusions: Abacavir represents a virologically effective replacement for d4T, PI, or NNRTI in persons on successful first-line therapy. Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides. Replacement of d4T with ABC leads to modest improvements in fat mass.

Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns.

Abstract: Adipose tissue alterations (ATAs) were clinically assessed in 2258 HIV-1-infected outpatients consecutively observed in 6 Italian clinical centers and were found to be present in 29.5% of the men and 41.9% of the women. A logistic regression model including age, HIV disease Centers for Disease Control stage, CD4 cell counts, HIV RNA load, the duration of antiretroviral therapy, the number of drugs taken, and the use of d4T showed that men had a 0.47 adjusted risk of presenting with ATAs (95% CI: 0.38-0.58, P < 0.0001). The risks of having ATAs (except circumscribed lipomas) in any body region, presenting with fat accumulation, or being affected by combined forms of ATA were also lower in men, whereas the risk of developing pure lipoatrophy was similar in the 2 genders. Our results indicate that women are at higher risk of developing antiretroviral treatment-related ATAs and show a particular and complex ATA pattern.

Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome.

Abstract: Objectives: To assess incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART). Methods: Seven hundred fifty-five HIV-seropositive patients consecutively prescribed new ART were selected. Liver function tests were assessed at baseline, after I month, and every 4 months thereafter. Liver biopsy was recommended in case of SH (i.e., increase in liver enzymes ≥ 10 times the upper limit of normal or 5 times baseline if markedly abnormal). Results: Twenty-six cases of SH were observed with an incidence of 4.2% person-years. Liver failure (LF) was rarely seen (1.1 per 100 person-years). Liver damage was invariably observed in patients with chronic viral hepatitis. Liver histology showed exacerbation of viral hepatitis in all 16 patients for whom a liver biopsy was available at the time of SH. A direct correlation was found between alanine aminotransferase increase and increase in CD 4+ T-cell count in patients with SH (r = 0.53, p <.001). Death occurred during follow-up in 7 of 26 (27%) patients, all of whom showed LF and baseline CD 4+ count less than 20 cells/mm 3 (7/7 patients = 100% vs. 8/19 patients without LF; p <.01). Relapse of SH was observed after ART was recommenced in 7 of 17 (41% patients. Five of these 7 patients did not show further SH relapse after treatment with interferon. Conclusions: This study provides estimates of SH and LF in a large population-based setting where hepatitis C virus coinfection is highly prevalent and provides indications that liver damage may be caused by immune reconstitution and related exacerbation of viral hepatitis. A strict follow-up for hepatotoxicity is mandatory when ART is initiated in patients with <200 CD4 + T cell/mm 3 . Antihepatitis pre- or co-medication could be an effective preventive or curative measure.