Effect of alcohol consumption on all-cause and liver-related mortality among HIV-infected individuals.

OBJECTIVES: The aim of the study was to examine the association between levels of past and current alcohol consumption and all-cause and liver-related mortality among people living with HIV (PLWH). METHODS: A prospective cohort study of 1855 PLWH in Baltimore, MD was carried out from 2000 to 2013. We ascertained alcohol use by (1) self-report (SR) through a computer-assisted self interview, and (2) medical record abstraction of provider-documented (PD) alcohol use. SR alcohol consumption was categorized as heavy (men: > 4 drinks/day or > 14 drinks/week; women: > 3 drinks/day or > 7 drinks/week), moderate (any alcohol consumption less than heavy), and none. We calculated the cumulative incidence of liver-related mortality and fitted adjusted cause-specific regression models to account for competing risks. RESULTS: All-cause and liver-related mortality rates (MRs) were 43.0 and 7.2 per 1000 person-years (PY), respectively. All-cause mortality was highest among SR nondrinkers with PD recent (< 6 months) heavy drinking (MR = 85.4 deaths/1000 PY) and lowest among SR moderate drinkers with no PD history of heavy drinking (MR = 23.0 deaths/1000 PY). Compared with SR moderate drinkers with no PD history of heavy drinking, SR nondrinkers and moderate drinkers with PD recent heavy drinking had higher liver-related mortality [hazard ratio (HR) = 7.28 and 3.52, respectively]. However, SR nondrinkers and moderate drinkers with a PD drinking history of > 6 months ago showed similar rates of liver-related mortality (HR = 1.06 and 2.00, respectively). CONCLUSIONS: Any heavy alcohol consumption was associated with all-cause mortality among HIV-infected individuals, while only recent heavy consumption was associated with liver-related mortality. Because mortality risk among nondrinkers varies substantially by drinking history, current consumption alone is insufficient to assess risk.

Racial and ethnic disparities in COVID-19 disease incidence independent of comorbidities, among people with HIV in the US.

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

Assessing effects of behavioral intervention on treatment outcomes among patients initiating HIV care: Rationale and design of iENGAGE intervention trial.

During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining "HIV adherence" and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or "treatment cascade," an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200 c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence.

Pneumocystis prophylaxis and survival in patients with advanced human immunodeficiency virus infection treated with zidovudine. The Zidovudine Epidemiology Group.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine. METHODS: A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome-related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival. RESULTS: Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim-sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim-sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP. DISCUSSION AND CONCLUSIONS: Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease.

Neutropenia and bacterial infection in acquired immunodeficiency syndrome.

BACKGROUND: In human immunodeficiency virus (HIV) disease, neutropenia occurs most commonly in patients who are also severely immunosuppressed. It is not currently known whether neutropenia is an independent risk factor for the development of bacterial infection, which is a potentially serious complication of advanced HIV disease. METHODS: We compared the incidence of bacterial infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1 x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use of injecting drugs, and follow-up time from a demographically heterogeneous urban cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins Hospital. The incidence of serious infection was analyzed separately for patients with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. RESULTS: There were no statistically significant associations found between neutropenia and several individual bacterial infections, including bacteremia, pneumonia, endocarditis, bacterial enterocolitis, and infection of normally sterile sites for any level of neutropenia. However, for all these infections combined, the adjusted relative risk for the occurrence of bacterial infection was 2.33 (95% confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than 1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial infection ranged from two to three infections per 100 person-months of neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five infections per 100 person-months of neutropenia for patients with an ANC of less than 0.5 x 10(9)/L for all bacterial infections combined. CONCLUSIONS: Our matched cohort analysis indicates that neutropenia is an independent risk factor for bacterial infection in patients with advanced HIV disease. Given the incidence of infection, the cost-effectiveness of interventions to prevent neutropenia in advanced HIV disease should be assessed.

Duration of the survival benefit of zidovudine therapy in HIV infection.

BACKGROUND: Zidovudine therapy improves survival in advanced human immunodeficiency virus (HIV) infection and delays progression from earlier stages to advanced stage of HIV disease. The duration of the benefit of zidovudine therapy, however, may be limited. OBJECTIVE: To quantitate the duration of the survival benefit of zidovudine therapy in a heterogeneous patient population receiving care for HIV infection in an urban clinic. METHODS: We analyzed data from 393 HIV-infected patients with CD4+ cell counts of 0.5 x 10(9)/L (500 cells/microliter.) or less who first presented for care at The Johns Hopkins HIV Clinic, Baltimore, Md, from July 1989 through December 1993. Follow-up extended to a maximum of 3 years (median, 2 years). Survival probabilities in patients who received and who did not receive zidovudine therapy were analyzed by Kaplan-Meier methods and by multivariate Cox proportional hazards regression analysis adjusting for both time-dependent and fixed prognostic covariates. RESULTS: Adjusting for baseline differences in CD4+ cell count, clinical stage of HIV disease, and prophylaxis for Pneumocystis carinii pneumonia, Cox regression analysis showed a significant effect of zidovudine compared with no treatment on the risk of dying during the first year of therapy (relative hazard for death, 0.32; 95% confidence interval [CI], 0.18 to 0.59). However, analysis of the time-dependent effect of zidovudine therapy showed that there was a diminishing relative hazard between treatment and no treatment of 0.75 (95% CI, 0.45 to 1.26) at 1 to 2 years of therapy and a relative hazard of 1.61 beyond 2 years (95% CI, 0.70 to 3.71). CONCLUSION: The survival advantage of zidovudine therapy is time dependent, lasting between 1 and 2 years in patients with CD4+ cell counts of 0.5 x 10(9)/L or less. Alternative antiretroviral treatment may be indicated at that time.

A case study of physicians' use of liver-spleen scans. Are we doing what we think we're doing?

We evaluated physicians' perceptions of the performance capabilities of the liver-spleen scan (LSS) in detecting metastases and the inferences physicians draw from LSS results. Physicians' perceptions of the sensitivity and specificity of the LSS in detection of metastases, as well as their estimates of likelihood ratios for various scan results, varied broadly over a range that could result in clinically important variations in patient treatment. In addition, independent of any variations in estimates of test performance characteristics, physicians had difficulty drawing appropriate probabilistic inferences from LSS results. Our findings suggest that data regarding the performance capabilities of the LSS and other diagnostic tests within a particular hospital should be made available to physicians and that physicians should be given microcomputer assistance in estimating the impact of test results on the probability of disease.

Risk factors for Kaposi's sarcoma in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group.

BACKGROUND: Although the cause of Kaposi's sarcoma (KS) is unknown, its unique epidemiology suggests that an infectious, sexually transmitted agent or agents may contribute to its pathogenesis. METHODS: To assess the natural history of KS associated with the acquired immunodeficiency syndrome and to identify factors associated with its development, data were analyzed from a multicenter, observational cohort study of 1044 persons with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex and a total CD4 cell count of less than 0.25 x 10(9)/L who were treated with zidovudine between April 1987 and April 1988. Records were reviewed bi-monthly. Follow-up continued for 2 years or until death. RESULTS: One hundred thirty-one patients (13%) had KS a study enrollment, and 143 developed KS (14%) during follow-up, with a 2-year actuarial risk of 21%. The probability of KS at 2 years for patients with initial CD4 cell counts of less than 0.1 x 10(9)/L was 25%, compared with 15% for those with counts of 0.1 x 10(9)/L or more. By logistic regression, a baseline CD4 cell count of less than 0.1 x 10(9)/L (relative odds, 1.43; 95% confidence interval, 1.04 to 1.95), homosexuality (relative odds, 3.71; 95% confidence interval, 1.82 to 7.56), cytomegalovirus disease (relative odds, 1.56; 95% confidence interval, 1.01 to 2.41), and white race (relative odds, 1.64; 95% confidence interval, 1.11 to 2.43) were independently associated with KS. Median survival after KS was 408 days, and KS was an independent predictor of death (relative hazard, 1.78; 95% confidence interval, 1.26 to 2.52). CONCLUSIONS: Kaposi's sarcoma contributes to human immunodeficiency virus-related morbidity and mortality, especially among male homosexuals. This large cohort study provides further evidence for an association between risk for cytomegalovirus infection and KS.

Analysis of physician and hospital differences in 'negative' coronary angiogram rates.

A direct relationship has been postulated between high "negative" coronary angiogram rates and physician payment. We conducted a prospective study of coronary angiography in a teaching and community hospital staffed, respectively, by cardiologists who were performing cardiac catheterization as salaried or fee-for-service physicians. The lower overall rate of negative angiograms at the teaching hospital correlated with the presence of a cardiac surgery unit and the increased referral of patients with documented coronary artery disease. The percentage of completely normal angiograms did not differ significantly between hospitals. The number of angiograms positive by a 70% occlusion criterion in patients not previously known to have coronary artery disease also did not differ greatly. Negative angiogram rates appeared to vary inversely with physician ability to set preangiogram probabilities of coronary artery disease. Our findings do not discount reimbursement as a strong incentive, but suggest other important determinants of coronary angiographic variation.

Long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Zidovudine Epidemiology Study Group.

An epidemiologic study was initiated in 1987 to evaluate the long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Data from 886 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and CD4+ lymphocyte count less than 0.25 x 10(9)/L are reported. Eighteen-month survival was 67% for the cohort. Pretreatment factors associated with increased survival time included index diagnosis of AIDS-related complex, hematocrit of 0.35 or greater, CD4+ lymphocyte count of 0.15 x 10(9)/L or greater, high functional status, and time from diagnosis of AIDS to treatment of less than 60 days. By proportional hazards analysis, development of serious anemia was the most significant factor associated with early death. Receiving zidovudine for a high proportion of time significantly improved chances of survival even if anemia developed. Serious leukopenia occurring in 37% and serious anemia occurring in 32% of patients. Nonhematologic adverse events were uncommon and no previously unreported adverse events were seen.

Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs.

BACKGROUND: Pancreatitis is a known adverse effect of the nucleoside reverse transcriptase inhibitors, particularly didanosine. Hydroxyurea has been used to potentiate the antiviral efficacy of didanosine, but recently there has been concern that severe and even fatal pancreatitis may be more likely to occur when hydroxyurea is used in combination with didanosine. We investigated the incidence of pancreatitis in patients using nucleoside analogues with or without hydroxyurea. METHODS: Data were obtained from patients followed longitudinally on the Johns Hopkins HIV Clinic. Incidence rates of pancreatitis were calculated for each antiretroviral regimen that included zidovudine, stavudine, didanosine (+ hydroxyurea), and didanosine + stavudine (+ hydroxyurea). Poisson regression was used to compare the relative rate of pancreatitis for each regimen adjusting for other covariates. RESULTS: A total of 2613 patients received at least one of the nucleoside reverse transcriptase inhibitor-containing regimens. There were 33 cases of pancreatitis. The crude incidence rate of pancreatitis ranged from 0.18 cases per 100 person-years on therapy for zidovudine to 6.25 cases per 100 person-years for didanosine + hydroxyurea. Compared to didanosine alone, and adjusting for CD4 cell count and other variables, the relative risk (RR) of pancreatitis was 8.56 [95% confidence interval) CI, 1.85-35.59] for didanosine + hydroxyurea, and 2.35 (95% CI, 0.46-11.89) for didanosine + stavudine + hydroxyurea. For any use of hydroxyurea, the RR = 4.01 (95% CI, 1.02-15.89). Other risk factors for pancreatitis included a CD4 cell count < 200 x 106 cells/l, female sex, and a history of pancreatitis. CONCLUSIONS: Our data show that the risk of pancreatitis is four-fold higher when hydroxyurea is used. The use of hydroxyurea with didanosine should probably be discouraged if other treatment options are available.

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.

Effectiveness of supervised, intermittent therapy for tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the effectiveness of supervised therapy for tuberculosis (TB) in patients with HIV infection. DESIGN: Retrospective, chart review. PATIENTS: Patients with TB and HIV infection. SETTING: Urban, public TB clinic. MAIN MEASURES AND RESULTS: A total of 107 patients with TB and HIV infection were studied. Most were men (78%), African American (91%), uninsured or on Medicaid (88%), and 67% were injecting drug users. TB was diagnosed before AIDS in 31% of subjects, at the time of AIDS in 32%, and after AIDS in 37%. Clinical features varied by stage of HIV disease. Sixteen patients received no therapy and died before TB was diagnosed, 10 died during the first 8 weeks of treatment. Seventy-eight patients received > 8 weeks therapy, of whom 48 (62%) were given directly observed therapy twice weekly and 30 (38%) received self-administered daily therapy. Patients who received directly observed therapy were more likely to complete 6 months of therapy (96 versus 76%, P = 0.02) and more likely to survive after therapy ended (85 versus 57%, P = 0.01). By logistic regression, directly observed therapy, AIDS diagnosed before TB, and age were significantly associated with survival outcome. CONCLUSION: Directly observed therapy for TB in patients with HIV infection is highly effective and associated with better adherence to therapy and survival.

Impact of opportunistic disease on survival in patients with HIV infection.

OBJECTIVE: To assess the impact of opportunistic diseases on survival in patients with HIV disease. METHODS: A cohort of 2081 patients followed for a mean of 30 months was studied. Time-dependent Cox proportional hazards analyses were performed using incident opportunistic diseases and CD4 cell counts as independent variables. RESULTS: During follow-up, 730 (35%) patients died. The occurrence of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) disease, Mycobacterium avium complex (MAC) disease, Candida esophagitis, Kaposi's sarcoma, lymphoma, progressive multifocal leukoencephalopathy (PML), dementia, wasting, toxoplasmosis, and cryptosporidiosis were all significantly associated with death, independently of CD4 cell count (all P<0.001 for opportunistic diseases controlling for CD4 cell count). The magnitude of increased risk was greatest for lymphoma [relative hazard (RH), 7.2], PML (RH, 3.9), MAC (RH, 3.0) and CMV (RH, 2.2). Cryptococcosis (RH, 0.94) and herpes zoster (RH, 0.85) were not associated with death. In a multivariate Cox proportional hazards analysis, MAC [RH, 2.56; 95% confidence interval (CI), 2.1-3.1], CMV (RH, 1.63; 95% CI, 1.3-2.1), toxoplasmosis (RH, 1.85; 95% CI, 1.3-2.6), PCP (RH, 1.29; 95% CI, 1.1-1.5), and CD4 cell count were significantly associated with death. Patients who had opportunistic diseases had significantly greatly monthly declines in CD4 counts (-11 x 10(6)/l per month) than those who did not (-6 x 10(6)/l per month; P <0.001). CONCLUSION: Most opportunistic diseases increase the risk of death independently of CD4 cell count. These data support the hypothesis that opportunistic diseases enhance HIV pathogenesis and further underscore the importance of prophylaxis.

Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea.

BACKGROUND: Sensory neuropathy is a common adverse effect of the nucleoside analogue anti-retroviral drugs didanosine (ddl) and stauvudine (d4T). These drugs are increasingly being used in combination, and it is not currently known whether the incidence of neuropathy is higher with combination compared to individual drug use. It is also not known if hydroxyurea, used to potentiate the antiviral efficacy of these drugs, may also increase the risk of neuropathy. The purpose of this analysis is to investigate if the combination of ddl and d4T, with or without hydroxyurea, has a higher incidence of neuropathy than a single drug regimen. METHODS: Data were obtained from patients followed longitudinally by the Johns Hopkins AIDS Services. Incidence rates of development of neuropathy were calculated for each of five regimens: ddl (+/- hydroxyurea), ddl + d4T (+/- hydroxyurea), and d4T. Cox proportional hazard regression was used to compare the relative risk of neuropathy for each regimen adjusting for CD4 cell count, other drugs received, and time on therapy. RESULTS: A total of 1116 patients received at least one of the five regimens. There were 117 cases of neuropathy. The crude incidence rate of neuropathy ranged from 6.8 cases per 100 person-years for ddl to 28.6 cases per 100 person-years for ddl + d4T + hydroxyurea. Compared with ddl alone, and adjusting for CD4 cell counts and other variables, the relative risk of neuropathy was 1.39 [95% confidence interval (CI): 0.84-2.32] for d4T alone, 2.35 (95% CI: 0.69-8.07) for ddl + hydroxyurea, 3.50 (95% CI: 1.81-6.77) for ddl + d4T, and 7.80 (95% CI: 3.92-15.5) for ddl + d4T + hydroxyurea. CONCLUSIONS: Based on the data, the risk of neuropathy is additive or even synergistic for ddl + d4T + hydroxyurea compared with ddl or d4T alone. The combination of ddl + d4T also increases the risk of neuropathy but less than when hydroxyurea is included.

Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients.

OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from prospective observational database. METHODS: Patients were ZDV-experienced if they had previously received more than 90 days of ZDV and ZDV-naive if they had never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12 months after initiation of D4T. Univariate and multivariate analyses were performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race, HIV transmission category, time since enrollment, and protease inhibitor use. RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n = 98) patients in age, sex, race, transmission category, use of a concurrent protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39), in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or 6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a repeated measures analysis, there was no significant difference in achieving undetectable HIV-1 RNA or in CD4 cell response between experienced and naive patients. CONCLUSION: No difference in response to a D4T-containing regimen between ZDV-experienced and naive patients was found over a 1-year period. In contrast to previous trials, most patients in this study also received a protease inhibitor. These findings may be more relevant in the current era of highly active antiretroviral therapy.

Adverse events from drug therapy for human immunodeficiency virus disease.

PURPOSE: Drug therapies for patients with human immunodeficiency virus (HIV) infection are associated with adverse events that can potentially limit their effectiveness. We sought to quantify the incidence of these events in clinical practice and determine whether there were demographic and clinical differences in adverse event rates for these drugs. PATIENT AND METHODS: We calculated specific and overall adverse event rates from use of zidovudine, didanosine, zalcitabine, cotrimoxazole, and dapsone in an observational urban cohort of 1,450 HIV-infected patients with a CD4+ count of 500 cells/mm3 or less. We compared adverse event rates by gender, race, age, injecting drug use, and CD4+ count. RESULTS: Overall adverse event rates in order of incidence were dapsone, 16.2 per 100 person-years (PY); didanosine, 24.1 per 100 PY; zidovudine, 26.3 per 100 PY; cotrimoxazole, 26.3 per 100 PY; and zalcitabine, 37.0 per 100 PY. Rates increased significantly with decline in CD4+ count from > 200 to < 100 cells/mm3 for all drugs but dapsone. In addition, women were more likely than men to have an adverse event for didanosine (relative risk [RR] = 2.7, P = 0.03) and from cotrimoxazole (RR 1.5; P = 0.05). Whites were at greater risk than blacks for adverse events from cotrimoxazole (RR = 1.6, P = 0.03). Only 22 of 357 total events (6%) required hospitalization, and there were no deaths. CONCLUSIONS: Adverse events from antiretroviral drugs and Pneumocystis carinii pneumonia prophylaxis that interrupt therapy are relatively common, although serious events requiring hospitalization are rare. Adverse event rates increase progressively with decline in CD4+ count. The gender and race of the patient modify the risk of adverse events for some drugs.

Treatment of anemia in patients with HIV infection, Part 1: The need for adequate guidelines.

Anemia in HIV-infected individuals, still a common hematologic complication in the highly active antiretroviral therapy (HAART) era, is associated with shortened survival, increases in the rate of disease progression, and reduction in quality of life. Based on a thorough review of the literature, guidelines were developed for the assessment, diagnosis, monitoring, and treatment of anemia in patients with HIV/AIDS by a consensus committee consisting of nurses from academia and clinical practice. A major goal of this committee is to increase awareness within the nursing community of the prevalence of anemia in HIV-infected patients and its impact on their lives. Anemia developed in close to 90% of HIV-infected patients before the introduction of HAART, and it is still found in up to 46% of patients in the HAART era. Another goal is to encourage screening for anemia and the adaptation of a proposed classification system of anemia based on a graded decrease in hemoglobin levels.

Effects of age and sex on immunological and virological responses to initial highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has increased longevity. Currently, women comprise >50% of HIV-infected individuals worldwide. It is not known if there are differences between the sexes in the immunological and virological responses to HAART across the age strata. METHODS: Immunological reconstitution and virological response in the first 6 months of a first HAART regimen in two observational clinical HIV-infected cohorts were compared by both sex and age (>or=50 vs. <50 years old). RESULTS: A total of 246 individuals (28% women) were included in the study; 63 cases (>or=50 years old) and 183 controls (<50 years old). Over two-thirds of patients had HIV RNA levels <400 HIV-1 RNA copies/mL and CD4 count increases >or=50 cells/microL at 6 months from therapy initiation. There were no differences in immunological reconstitution across age and sex strata (P=0.81) and no differences in virological suppression, even after adjusting for type of HAART (P=0.68) or restricting the analysis to women only (P=0.81). These results suggest that younger and older women and men may have similar short-term initial HAART outcomes. CONCLUSIONS: Further evaluation of longer term clinical response to initial HAART regimen based on sex and age is indicated, especially with more efficacious and simplified antiretroviral regimens and the associated decrease in mortality.

Body shape and composition in HIV-infected women: an urban cohort.

OBJECTIVES: Alterations in body shape and composition are associated with HIV/AIDS. Wasting remains prevalent; increasingly, lipodystrophy is reported. Obesity is also epidemic in the USA. In this study, we sought to characterize the body changes reported by women attending a US urban clinic, and to evaluate contributing factors using inexpensive methods that are readily available in clinical practice. METHODS: In an urban Maryland clinic, a cross-section of HIV-infected women were evaluated by self report, anthropomorphic measurements, bioelectric impedance analysis (BIA) and chart review; they were categorized as no change, lipodystrophy, weight loss/wasting or weight gain/obesity. RESULTS: One hundred and sixty-one women were evaluated: 144 (89%) were African-American; 100 (62%) had used intravenous drugs and 40 (25%) were actively injecting drugs, while 39 (24%) smoked crack. Ninety-five (59%) were on highly active antiretroviral therapy (HAART) for a median period of 11.7 months [interquartile range (IQR)=4.5-24.2]. Since starting current HAART or in the previous year, 12 (7.4%) reported lipodystrophy changes, 85 (52.8%) weight gain, 27 (16.8%) overall weight loss, and 37 (23.0%) no change. Lipodystrophy was associated with higher CD4 percentage (P=0.03), lower frequency of crack use (P=0.04) and higher educational level (P=0.03). Weight loss correlated with longer duration of infection (P=0.01), select BIA results and increased rate of crack use (P=0.005). Weight gain was associated with higher fat mass (P=0.005), higher peak viral load (P=0.02), and lower rate of intravenous drug use (P=0.03). CONCLUSIONS: Self-reported changes in body shape were common. Obesity and complications of illicit drug use were more prevalent than lipodystrophy in this inner-city population of HIV-positive women.