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PubMed2002

Prospective study of infective endocarditis among injection drug users.

To determine the effect of human immunodeficiency virus (HIV) infection and other factors on infective endocarditis (IE) among injection drug users (IDUs), the incidence of IE was determined according to HIV status in a cohort of IDUs. A nested case-control study assessed IE risk factors. IE incidence (117 cases) was higher among HIV-seropositive than HIV-seronegative IDUs (13.8 vs. 3.3 cases/1000 person-years) during 1988-1998. Multivariate analysis of HIV-infected case patients revealed an inverse association between IE and CD4 lymphocyte count (odds ratio [OR] for 200-499 cells/mm(3), 2.01; OR for <200 cells/mm(3), 3.61) and with alcohol intake (OR for 1-21 drinks/week, 0.43; OR for >21 drinks/week, 0.32). Women had an increased risk of IE (OR, 3.26), as did persons with increasing injection drug use frequency (OR for less than daily use, 3.15; OR for at least daily use, 6.07). This study confirms that IE is more common among IDUs with advanced HIV immunosuppression even after accounting for injection drug use behaviors.

Adult↗
PubMed2002

Long-term metabolic consequences of switching from protease inhibitors to efavirenz in therapy for human immunodeficiency virus-infected patients with lipoatrophy.

The roles of nucleoside analogues and protease inhibitors (PIs) in the development of metabolic complications and fat-distribution abnormalities associated with highly active antiretroviral therapy (HAART) are not well known. We performed an observational study in which efavirenz was substituted for a PI for 41 patients receiving HAART who had prolonged virus suppression, clinical signs of severe lipoatrophy, hyperlipidemia, and insulin resistance. Clinical follow-up was performed for 1 year. Virus suppression was maintained in most of the patients, and a significant increase in CD4(+) lymphocyte count was observed, but no change in lipid profile or insulin resistance was observed. Abdominal fat content did not change, and subcutaneous fat depletion was even more pronounced >1 year after the switch. We conclude that, for PI-treated patients who present with lipoatrophy, hyperlipidemia, and insulin resistance, substituting efavirenz for PIs can maintain virus suppression and immunologic response to HAART, but it does not improve the lipid profile or resolve insulin resistance or lipoatrophy.

Adult↗
PubMed2002

Crack cocaine use and other risk factors for tuberculin positivity in drug users.

Two-step tuberculin testing and standardized interviews of 793 current and former drug users were performed to determine the risk factors for tuberculin positivity. The prevalence of tuberculin positivity was 25%. Factors independently associated with tuberculin positivity among participants seronegative for human immunodeficiency virus (HIV) included crack cocaine use (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.5), employment as a home health aide (adjusted OR, 2.1; 95% CI, 1.0-4.1), birth in Puerto Rico (adjusted OR, 2.2; 95% CI, 1.3-3.6), foreign birthplace (adjusted OR, 4.7; 95% CI, 1.6-13.6), African American race (adjusted OR, 2.5; 95% CI, 1.2-5.0), reported tuberculosis exposure (adjusted OR, 2.3; 95% CI, 1.2-4.4), and older age (adjusted OR, 2.9; 95% CI, 1.2-6.7). Additional risk factors among HIV-infected participants included alcoholism (adjusted OR, 2.4; 95% CI, 1.0-5.8) and high CD4(+) lymphocyte count. Identification of and administration of appropriate chemoprophylaxis to drug users with these risk factors should be given high priority.

Adult↗
PubMed2003

Relationship of Kaposi sarcoma (KS)-associated herpesvirus viremia and KS disease in Zimbabwe.

The relationship between Kaposi sarcoma-associated herpesvirus (KSHV) viremia and KS disease was investigated in 500 subjects who received treatment in Harare, Zimbabwe. Subjects were grouped by results of human immunodeficiency virus (HIV) type 1 serological tests, KS diagnosis, and KS clinical stage. The plasma KSHV DNA concentration was associated with concomitant KS and HIV-1 infection (AIDS-KS; P<.001) and AIDS-KS clinical stage (P=.01). Plasma KSHV DNA levels were greater in AIDS-KS than in matched HIV-1-seronegative KS (P=.04). The plasma KSHV DNA level was not associated with age, sex, systemic symptoms, or CD4+ lymphocyte count. Plasma and peripheral blood mononuclear cell KSHV DNA concentrations were linearly related (r2=.44; P<.001), and the nucleotide sequence of the K1 gene highly variable region was identical in both compartments. These findings provide evidence that KSHV viremia is common in advanced AIDS-KS in Zimbabwe and suggest a relationship between KSHV lytic replication and untreated HIV-1 infection.

Adolescent↗
PubMed2003

Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.

Adolescent↗
PubMed2003

Fluoroquinolone resistance in patients with newly diagnosed tuberculosis.

Fluoroquinolones are widely used for the treatment of bacterial infections and are also second-line therapy for tuberculosis. However, fluoroquinolone resistance in patients with newly diagnosed cases of tuberculosis is not routinely assessed. We performed in vitro susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones for all culture-confirmed tuberculosis cases in adults that were diagnosed at Johns Hopkins Hospital (Baltimore) between January 1998 and March 2002. Fifty-five patients were included in the study; 19 received fluoroquinolone monotherapy before the initiation of antituberculosis therapy. Two of 55 M. tuberculosis isolates (4%; 95% CI, 1%-13%) had decreased susceptibility to fluoroquinolones, including 2 of 19 of those from patients who had received fluoroquinolones (11%; 95% CI, 1%-33%) and 0 of 36 isolates from those who had not (95% CI, 0%-10%). The 2 fluoroquinolone-resistant M. tuberculosis strains were both from patients with acquired immunodeficiency syndrome and a CD4+ lymphocyte count of <50 cells/mm3. The incidence of M. tuberculosis fluoroquinolone resistance in this small sample of patients with newly diagnosed tuberculosis was high, particularly among patients with prior fluoroquinolone exposure.

Adult↗
PubMed2004

Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy.

Among 470 patients with acquired immune deficiency syndrome and/or human immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M mutation. The Q151M mutation was associated with younger age, lower CD4(+) lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens. By contrast, the Q151M mutation was inversely associated with lamivudine administration. A full reversion of the Q151M mutation was observed in 5 of 5 patients who underwent treatment interruption after GRT. The reversion was followed by a response to salvage therapy in 4 (80%) of 5 patients.

Adult↗
PubMed2004

Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy.

BACKGROUND: The associations of proteinuria and an elevated creatinine level with progression to acquired immunodeficiency syndrome (AIDS) and death in the era of highly antiretroviral therapy (HAART) have not been fully described. METHODS: This analysis includes 2038 human immunodeficiency virus (HIV)-infected women from the Women's Interagency HIV Study. Time to the development of a new AIDS-defining illness (ADI) and death was modeled using proportional hazards regression before the widespread availability of HAART and after initiation of HAART. RESULTS: Of the 2038 subjects, the 14.1% of women with proteinuria had lower CD4 lymphocyte counts and higher viral loads (P<.0001 for all) at baseline and before initiation of HAART. Before the widespread availability of HAART, proteinuria was associated with an increased risk for development of ADI (hazard ratio [HR], 1.37; P=.005), and proteinuria and an elevated creatinine level were both associated with an increased risk of death (for proteinuria: HR, 1.35 [P=.04]; for creatinine: HR, 1.72 per decrease in the inverse unit [P=.02]). Among women initiating HAART, an elevated creatinine level remained associated with an increased risk of development of ADI (HR, 1.54 per decrease in the inverse unit; P=.03), and proteinuria and an elevated creatinine level were associated with an increased risk of death (for proteinuria: HR, 2.07 [P=.005]; for creatinine: HR, 1.96 per decrease in the inverse unit [P=.04]). CONCLUSIONS: Proteinuria and an elevated creatinine level were associated with an increased risk of death and development of ADI. These associations may reflect the direct role of the kidney in modulating HIV disease, or they may act as markers of greater comorbidity.

Adult↗
PubMed2005

Coccidioidomycosis in persons infected with HIV type 1.

Coccidioidomycosis is a recognized opportunistic infection among persons infected with human immunodeficiency virus (HIV). Early in the HIV epidemic, most cases presented as overwhelming diffuse pulmonary disease with a high mortality rate. Although these cases are still seen, patients without significant immunodeficiency frequently present with a community-acquired pneumonia syndrome. Diagnosis can be established by cytological staining, culture, or serologic testing. All patients with HIV infection and symptomatic coccidioidomycosis should be treated with antifungal therapy. Severe cases frequently require a combination of therapy with amphotericin B and a triazole antifungal. Therapy for at least 1 year is recommended, but for patients with a focal pulmonary infection and peripheral blood CD4 lymphocyte counts of >250 cells/microL, it may be reasonable to stop therapy after this time. Other manifestations of coccidioidomycosis require prolonged therapy, and life-long treatment is recommended for persons with meningitis.

Antifungal Agents↗
PubMed1997

Mycobacterium kansasii disease in patients infected with human immunodeficiency virus.

We evaluated the presenting characteristics, response to therapy, and outcome for 46 patients infected with Mycobacterium kansasii and human immunodeficiency virus (HIV). M. kansasii infection occurred late in HIV disease (mean CD4 lymphocyte count, 52.4/mm3), when most patients had already developed AIDS; 91.3% of the patients had pulmonary involvement, and 21.7% had disseminated disease. Clinical and radiographic findings were consistent with pulmonary disease and had been present for approximately 4 weeks. Fourteen of the treated patients had disease that resolved or abated (mean survival +/- SE, 73.7 weeks +/- 14.6 weeks), and 13 had disease that persisted unchanged or worsened (mean survival +/- SE, 57.3 +/- 15.8 weeks). The outcome was poor for 17 patients who did not receive effective therapy (mean survival +/- SE, 14.1 +/- 5.3 weeks). M. kansasii infection presents late in the course of HIV disease, and the lung is the organ most frequently involved. Survival is clearly influenced by therapy, and even patients who respond poorly to therapy survive longer than those who are not treated.

AIDS-Related Opportunistic Infections↗
PubMed1997

Comparison of combination therapy regimens for treatment of human immunodeficiency virus-infected patients with disseminated bacteremia due to Mycobacterium avium. ANRS Trial 033 Curavium Group. Agence Nationale de Recherche sur le Sida.

We conducted a randomized, open-label trial in 42 French hospitals to compare the clinical and bacteriologic efficacy of combination therapy with clarithromycin/clofazimine (Clm/Clof) with that of combination therapy with clarithromycin/rifabutin/ethambutol (Clm/Rib/Eth) as treatment for Mycobacterium avium bacteremia. One hundred forty-four human immunodeficiency virus-seropositive patients older than 18 years of age who had CD4 lymphocyte counts of <100/mm3 and a blood culture positive for M. avium were enrolled in the study. The main measures of outcome were blood cultures, abatement of clinical symptoms (fever), and survival. Treatment success (defined as patient living, either no fever or a reduction of > or = 1 degrees C in initial body temperature, and a blood culture negative for M. avium) was similar in both treatment groups at months 2 and 6. However, following initial resolution of infection, relapse of M. avium bacteremia occurred in more patients in the Clm/Clof group than in the Clm/Rib/Eth group (22 vs. six, respectively; P < .001); these relapses were accompanied by emergence of strains resistant to clarithromycin in 21 and two patients, respectively. In conclusion, combination therapy with Clm/Rib/Eth prevented relapse of mycobacterial disease and, compared with combination therapy with Clm/Clof, was associated with a significant decrease in the emergence of resistant M. avium strains in HIV-infected patients treated for at least 28 weeks.

AIDS-Related Opportunistic Infections↗
PubMed1998

Favorable prognosis of purulent meningitis in patients infected with human immunodeficiency virus.

We prospectively reviewed all cases of purulent meningitis among human immunodeficiency virus (HIV) type 1-infected patients > 14 years old that occurred at the Hospital General Vall d'Hebron (Barcelona) during the period 1 January 1985 through 31 March 1997. There were 12 episodes of purulent meningitis in nine of 2,150 HIV-1-infected patients. The annual rate of purulent meningitis was 0.465 cases per 1,000 patients, a rate that is 150 times higher than that for the general population. During 10 episodes, CD4+ lymphocyte counts were < 200/mm3. The etiologic organism was Streptococcus pneumoniae in nine episodes (seven episodes occurred in four splenectomized patients), and Escherichia coli, Streptococcus agalactiae, and Enterococcus faecium each caused one episode. Clinical features and cerebrospinal fluid abnormalities were similar to those observed among patients without HIV-1 infection. All patients had bacteremia. The overall mortality was 8.3%. We conclude that purulent meningitis, particularly pneumococcal meningitis, is more frequent among HIV-1-infected patients than in the general population. The prognosis for HIV-1-infected patients is better than for HIV-1-negative patients.

Adult↗
PubMed1997

Endogenous interleukin-2 serum levels in children infected with human immunodeficiency virus.

Levels of interleukin-2 (IL-2) in serum obtained from human immunodeficiency virus (HIV)-infected children at health maintenance visits were measured to characterize endogenous IL-2 responses and to examine the association between these responses and progression of immunosuppression. IL-2 was detectable (level >8.7 pg/mL) in the serum of 28 of 45 HIV-infected children; 42% (19 of 45) had serum IL-2 levels of >39 pg/mL. Children without evidence of immunosuppression (Centers for Disease Control and Prevention Pediatric HIV Classification Immunologic Category 1, n = 15) and children with severe immunosuppression (immunologic category 3, n = 20) had statistically significant lower serum IL-2 levels (mean +/- [SD], 134.4 +/- 227.3 pg/mL and 18.2 +/- 30.3 pg/mL, respectively) than those with moderate immunosuppression (mean +/- [SD], 450.5 +/- 311.8 pg/ml; immunologic category 2, n = 10) (P < .05, Wilcoxon rank sum test). In those children in whom immunosuppression was evident, decreasing serum IL-2 levels correlated with depletion of CD4+ lymphocytes (r = 0.74), whereas there was an inverse correlation between serum IL-2 levels and CD4+ lymphocyte counts (r = -0.47) in children with no or moderate immunosuppression.

Child↗
PubMed1997

Effect of treatment with zidovudine on subsequent incidence of Kaposi's sarcoma.

Despite much investigation of zidovudine, little has been reported regarding its effect on the development of most individual AIDS-defining illnesses, including Kaposi's sarcoma (KS). We used observational data from the Multicenter AIDS Cohort Study (MACS) to estimate the effect of zidovudine use on the subsequent incidence of KS. To do this, we examined and adjusted for predictors of zidovudine use. CD4 lymphocyte counts, the development of HIV-related symptoms and AIDS, and changes in these factors were important predictors of zidovudine use. We used these associations to control for confounding by these and other factors with the G-estimation approach. We found no evidence that zidovudine use affected the time to KS in the MACS; the point estimate (95% confidence interval [CI]) for increase in time to KS was zero (-28%-68%). The relative risk was 1.0 (95% CI, 0.54-1.84). Randomized trials suggest that zidovudine may prevent KS. We discuss possible explanations for differences between results.

AIDS-Related Opportunistic Infections↗
PubMed1997

Reactivation of Chagas' disease in patients with AIDS: report of three new cases and review of the literature.

Three new cases of reactivation of Chagas' disease in patients with AIDS, with central nervous system and/or cardiac involvement, are reported. One patient had histological evidence of acute esophageal and gastric Trypanosoma cruzi myositis, a previously unrecognized finding in patients with reactivated Chagas' disease. The patients had a low CD4 lymphocyte count and had other AIDS-defining opportunistic infections. One patient's condition improved with benznidazole therapy. Analysis of these three cases and review of the 13 others published in the literature revealed that the central nervous system is the most commonly involved site (75%), followed by the heart (44%). Early diagnosis and treatment with benznidazole or nifurtimox probably improve the survival rate. Long-term secondary prophylaxis should be recommended for patients who respond to therapy, although it is uncertain which drug to use for this purpose. T. cruzi should be included in the list of opportunistic pathogens causing infection in severely immunocompromised patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2000

Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals.

A 32-amino acid HIV-1 Gag immunogen was assessed for its ability to augment existing virus-specific CTL responses in chronically HIV-1-infected individuals. The immunogen was an HIV-1 synthetic lipopeptide conjugate composed of an N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R)-propyl-N-(R)-cysteinyl] group covalently coupled to a synthetic 32-amino acid Gag peptide containing at least 5 CTL epitopes known to be restricted by HLA-A33, -B8, -B27, -B35, and -Bw62. This potential immunotherapeutic was first determined to be safe in six HIV-1-seropositive subjects, with no adverse clinical effects noted during a 182-day period after administration of a dose of 350 microg. The immunogenicity of this lipopeptide conjugate was then assessed in a pilot study in nine HIV-1-seropositive volunteers with peripheral blood CD4+ lymphocyte counts of >500/microl. Three groups of individuals were studied: HLA-selected subjects who received 350 microg of the immunogen on days 0, 28, and 56 (four subjects); HLA-selected subjects who received a placebo according to a similar inoculation schedule (three subjects); and HLA-mismatched subjects who received the experimental immunogen (two subjects). All subjects were monitored for 26 weeks. After treatment, PBLs from two of the four HLA-selected subjects who received the experimental immunogen showed a transient increase in Gag peptide-specific bulk CTL activity. None of the placebo-vaccinated or vaccinated HLA-mismatched subjects showed any change in bulk Gag peptide-specific CTL activity. However, no consistent decrease in plasma HIV-1 RNA levels was noted in any of the subjects. The present study illustrates that this peptide formulation may not be a sufficiently potent immunogen to significantly augment HIV-1-specific CTLs and to decrease virus load in HIV-1-seropositive individuals.

AIDS Vaccines↗
PubMed2002

Determination of genetic subtypes of HIV type 1 isolated from Korean AIDS patients.

To determine HIV-1 subtypes in Korean patients, we analyzed the nucleotide sequences of the HIV-1 env gene isolated from 19 Korean patients. DNA was extracted from cultured lymphocytes and the proviral V3 env gene was amplified by nested polymerase chain reaction. DNA sequences were determined using a cycle sequencer with fluorescence-labeled dye terminators, and aligned using a set of reference sequences. The phylogenetic tree was constructed by the neighbor-joining method. Most of the enrolled patients were in the advanced stage of AIDS with CD4+ lymphocyte counts ranging from 10 to 560 (median 50) per mm3. Eighteen of the nineteen patients' sequences fall into subtype B (95%) and one was subtype A (5%). The tetrameric motifs at the tip of the V3 loop were comprised of GPGR (10 cases, 53%), GPGS (5 cases, 26%), and GPGQ, GPGG, GQGR, and APGS (one case each, 5%). Subtype B was found to be the most predominant clade of HIV-1 in our AIDS patients.

Adult↗
PubMed2001

Gender differences in perceived health-related quality of life among patients with HIV infection.

This article explores how a group of human immunodeficiency virus (HIV)-infected patients perceived their health-related quality of life (HRQOL) in relation to their coping capacity expressed as sense of coherence. The emphasis was on gender differences. The sample consisted of 55 women (29%) and 134 men (71%), receiving outpatient medical care in a hospital. Self-report instruments, the health index, the HIV symptom scale, the well-being scale, the sense of coherence (SOC) scale and the Interview Schedule for Social Interaction were used. Disease status (HIV CDC classification, absolute CD4+ lymphocyte count and HIV/RNA) was also measured, and demographic data were collected. The total sample scored significantly worse self-rated health and weaker SOC than healthy controls. The HIV-infected women were significantly younger than the men (p < 0.0001). The majority of the women (60%) were infected by heterosexual transmission and of the men (58%) by homosexual/bisexual contacts. In the univariate analysis the women scored significantly less positive well-being (p < 0.05), weaker SOC (p < 0.05), and less social support (p < 0.01) than the men despite less advanced disease. Multiple regression analyses revealed that SOC was the strongest predictor of subjective HRQOL in both genders. The results suggest that health professionals who individualize their care of HIV-infected patients should try to be sensitive to the different ways in which men and women express their HRQOL.

Antiviral Agents↗