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Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis.

RATIONALE: Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. OBJECTIVE: To evaluate the activity of intermittent rifabutin-based therapy. METHODS: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. MEASUREMENTS: Culture-positive treatment failure or relapse. MAIN RESULTS: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10 copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs. CONCLUSIONS: Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.

AIDS-Related Opportunistic Infections↗

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

Adolescent↗

Influence of a monocyte chemoattractant protein 1 mutated allele on the response to protease inhibitor-based antiretroviral therapy.

BACKGROUND: Antiretroviral drug efficacy has been widely studied in relation to viral factors. Mutations in the HIV co-receptors and their natural chemokines, however, may be critical in HIV infection and treatment response. We compared the efficacy of protease inhibitor (PI) treatment among PI-naïve patients grouped according to whether they carried the chemokine CC motif receptor 2 (CCR-2) 64I and monocyte chemoattractant protein 1 (MCP-1)-2518G alleles. METHODS AND RESULTS: HIV-infected patients who were PI-naive were selected for the study (n=164) but there was no restriction on lymphocyte CD4 count or plasma HIV viral load. Follow-up was for the first 24 months of treatment. Clinical and laboratory data were obtained every 3 months. All the participants were genotyped for the MCP-1-2518G, CCR-2 64I, CCR-5Delta32 and stromal derived factor 1 (SDF1) 3'A mutated alleles. The results indicated that patients carrying the mutated allele of MCP-1 had a higher mean CD4 cell count throughout the follow-up period than those with the common allele (P=0.01). Also, patients with the MCP-1 and CCR-2 mutated alleles were more likely to continue to have an undetectable viral load following treatment (P=0.05). CONCLUSION: A better response to PI treatment appears to be conferred by mutations in the host MCP-1 and CCR-2 genes, and may be related to the cellular axis-of-entry used by the retrovirus.

Adult↗

CD4+ lymphocyte response to zidovudine as a predictor of AIDS-free time and survival time.

It is unknown whether the early rise in CD4+ lymphocyte count seen in zidovudine-treated patients is associated with increased AIDS-free time and survival time. To determine the association of this and other changes in immunologic and hematologic markers with prognosis for time to AIDS and survival, we followed 747 AIDS-free patients from initiation of zidovudine therapy in the Multicenter AIDS Cohort Study (MACS). Participants were seen semiannually and had data collected on medication use, immunologic and hematologic variables, and clinical outcomes. AIDS was diagnosed in 216 participants and 165 died during the median follow-up period of 2.0 years. Duration of zidovudine use was categorized into 1-6 months (after 6 months of follow-up) and 7-12 months (12 months of follow-up). During the 6-month follow-up period in which zidovudine was first used, CD4+ lymphocyte levels rose by 17 cells/microliters compared with a mean decrease of 30 cells/microliters/6 months in untreated individuals (after adjusting for baseline CD4+ lymphocyte count). Baseline levels of CD4+ lymphocytes, platelets, and hemoglobin were significant predictors of AIDS and death. After 1-6 months with patients taking zidovudine and controlling for baseline (pretreatment) variables, change in markers after 6 months of follow-up and use of Pneumocystis carinii pneumonia prophylaxis and other antivirals, change in CD4+ lymphocyte count significantly predicted progression to AIDS [relative hazard (RH) = 0.71 for each 100 cell/microliters increase, p = 0.0001] and survival (RH = 0.78 per 100 cell/microliters increase; p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[Osteonecrosis in HIV-infected patients and its correlation with highly active antiretroviral therapy (HAART)].

INTRODUCTION: The incidence of osteonecrosis has increased in HIV-infected patients over the last few years, and has been considered as a side effect of highly active antiretroviral therapy (HAART), possibly related to drug-induced hyperlipidemia. We report seven cases. OBSERVATIONS: Seven HIV-infected persons, 6 males and one female, aged 29 to 49 years, and with advanced immunodeficiency (lymphocyte CD4 count<250 cells/mm3 in all the cases). Osteonecrosis generally involved the head of the femoral, clinically presented pain and difficulty walking, and was diagnosed by magnetic resonance imaging or skeletal scintigraphy. COMMENTS: Among these 7 patients with osteonecrosis, only 4 received antiretroviral therapy at the time of the diagnosis, one presented moderate hypertriglyceridemia, and 3 had positivity for the anti-phospholipid antibodies. Hence, HAART, dyslipidemia, and auto-immunity may enhance, but are not necessarily elements in the onset of HIV-associated avascular bone necrosis.

Acquired Immunodeficiency Syndrome↗

Bacterial pneumonia in hospitalized patients with HIV infection: the Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study.

STUDY OBJECTIVES: To describe the causative organisms and factors associated with bacterial pneumonia and to assess its impact on the outcome of hospitalized patients with HIV. DESIGN: Prospective, observational. SETTING: A university-affiliated medical center. METHODS: We included 1,225 consecutive hospital admissions, from April 1995 through March 1998, of 599 adults with HIV. We collected data on APACHE II (acute physiology and chronic health evaluation II) score, leukocyte and CD4+ lymphocyte counts, length of hospital stay, ICU admission rate, and case-fatality rate. Chest radiographs and laboratory results were reviewed. The presence of bacterial pneumonia was noted. RESULTS: Bacterial pneumonia was diagnosed in 111 hospitalizations (9%): 80 (72%) were community-acquired infections. The CD4+ lymphocyte count was lower (median, 38 vs 66/microL, p = 0.0027), APACHE II score higher (17 vs 13, p < 0. 0001), length of hospital stay longer (median, 6 vs 4), and ICU admission (28% vs 9%) and case-fatality rates (21% vs 4%) higher in patients with bacterial pneumonia compared with those without bacterial pneumonia. The most common pathogen was Pseudomonas aeruginosa (32 admissions), followed by Streptococcus pneumoniae (22 admissions), Staphylococcus aureus (16 admissions), and Haemophilus influenzae (11 admissions). Thirty-three (30%) of the pneumonias were bacteremic. Bacteremia was more common in pneumococcal than in pseudomonal pneumonia (95% vs 9%, p < 0.0001). Compared with patients with pneumococcal pneumonia, patients with pseudomonal pneumonia had lower leukocyte and CD4+ lymphocyte counts, longer hospital stay, and similar case-fatality rate. CONCLUSIONS: P aeruginosa is becoming a common cause of both community-acquired and nosocomial bacterial pneumonia in hospitalized patients with HIV, especially in those with low leukocyte and CD4+ lymphocyte counts.

AIDS-Related Opportunistic Infections↗

Etiologies and manifestations of persistent diarrhea in adults with HIV-1 infection: a case-control study in Lima, Peru.

UNLABELLED: OBJECTIVE We sought to determine the etiologies, manifestations, and risk factors for persistent (> or =7 days) diarrhea in human immunodeficiency virus type 1 (HIV-1)-infected persons in Peru. DESIGN: The present study is a case-control study of 147 HIV-1-infected case subjects with persistent diarrhea and 147 HIV-1-infected control subjects without diarrhea. METHODS: We obtained clinical, demographic, and exposure data, CD4 lymphocyte counts, and stool samples for detection of enteric parasitic and bacterial pathogens and rotavirus. RESULTS: One or more enteric pathogen was identified in 55% of case subjects and 21% of control subjects (odds ratio adjusted for CD4 lymphocyte count, 3.8; 95% confidence interval, 2.2-6.5). The median CD4 lymphocyte count was highest with pathogen-free diarrhea and lowest with Cryptosporidium infection. Cryptosporidium species (the most frequent pathogen), Giardia lamblia, Aeromonas species, Campylobacter species, and rotavirus were all significantly associated with diarrhea. Bacterial pathogens were significantly associated with G. lamblia and rotavirus infection. Of the bacterial pathogens (Aeromonas, Campylobacter, Salmonella, and Vibrio species and enterotoxigenic Escherichia coli), only 24% were susceptible to cotrimoxazole, whereas 90% were susceptible to ciprofloxacin. In no case did the sensitivity or positive predictive value of specific clinical and laboratory findings for curable enteric infections exceed 50%. CONCLUSIONS: Several enteric pathogens were associated with diarrhea in HIV-1-infected case subjects in Peru, especially among those who were heterosexual. Clinical findings were poor predictors of detectable microbial etiology. The guidelines for initial management of chronic diarrhea with sulfamethoxazole-trimethoprim in HIV-1-infected persons require revision, at least in settings where prophylaxis with this agent is common.

Adult↗

Changes in AIDS-defining illnesses in a London Clinic, 1987-1998.

OBJECTIVES: To describe the incidence of AIDS-defining illnesses within a single large clinic setting, to describe temporal changes over a 10-year period in the overall incidence and of individual AIDS-defining illnesses and to investigate the impact of HIV treatment regimen on the incidence of AIDS-defining illnesses. SUBJECTS AND METHODS: A person-years analysis was used to determine the incidence of AIDS-defining illnesses according to calendar year and stratification by CD4 lymphocyte count and treatment regimen in 1806 patients from the Royal Free Centre for HIV Medicine with at least one CD4 lymphocyte count and follow-up visit. RESULTS: Prior to 1992, the incidence of all AIDS-defining illnesses was 27.4/100 person-years of follow-up (PYFU; 95% confidence interval [CI], 22.8-32.0) and during 1997 this incidence had dropped to 6.9/100 PYFU (95% CI, 4.7-9.1; p < .0001, test for trend). The decline in incidence over time occurred in esophageal candidiasis, cytomegalovirus disease (including retinitis), Kaposi's sarcoma, lymphoma, wasting syndrome, and Pneumocystis carinii pneumonia (p < .05, test for trend), but there was no evidence of a decline in AIDS dementia or in Mycobacterium avium complex. In 1997, among patients with CD4 lymphocyte counts of < or =200 cells/mm3, the incidence rates for any AIDS-defining illness was 51.1/100 PYFU for patients taking no therapy (95% CI, 27.9-85.7), 34.5 among patients on monotherapy (95% CI, 4.2-124.6), 13.2 among patients taking dual combination therapy (95% CI, 3.6-33.8) and 6.1 among patients taking triple therapy or more complex regimens (95% CI, 0.7-22.0; p < .0001, test for trend). CONCLUSIONS: There was a considerable decline in AIDS-defining illnesses during 1996 and 1997, coinciding with the rapid development of new antiretroviral treatments and combinations of treatment. Further follow-up of large observational cohorts is essential to monitor the incidence of diagnoses less common than we were able to consider, such as tuberculosis, cryptosporidiosis, and cryptococcosis, and also to investigate whether the incidence of disease continues to fall, or whether it starts to rise again, as toxicities, compliance, drug resistance, and long-term side effects begin to appear.

AIDS Dementia Complex↗

[Correlation between mantoux and tuberculin's fraction from delayed hypersensitivity skin test, in a cohort from HIV-1 positive patients, in function of immunodeficiency level, and active tuberculosis incidence].

OBJECTIVES: The aim of this work was to assess cellular immunity using the multitest CMI and relate its results with lymphocyte CD4 counts, and the risk to developed active tuberculosis if the multi-test's tuberculosis pápula was positive. METHODS: Prospective longitudinal follow-up of 342 IDU patients, 210 infected with HIV-1 and seronegative 132 patients. The cohort study was 165 IDU HIV-1 positive patients (128 men, 37 female). Ages was 18 to 45 years. Study time were 25 months (8-25). Tuberculin skin tests and multitest IMC were performed at baseline and each three months, and screening from active tuberculosis were performed all study when necessary was considered. RESULTS: Actived tuberculosis developed in 9.25 cases per one hundred persons and year from follow-up in the ranges with better immunologic status (Score from PHR > 10 mm). There are an significative correlation between tuberculosis skin test diameter and PHR tuberculin fraction papula. CONCLUSIONS: PHR performed with Multitest IMC is an useful test to evaluate cellular immune system, and HIV-1 positive patients with energy in this test or positive tuberculine fraction must be considered to isoniazid (9 months) prophylaxis.

AIDS-Related Opportunistic Infections↗

Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+ T lymphocyte count and detection of EBV, CMV and HSV.

Viral coinfection in the oral cavity associated to HIV infection was evaluated in 180 children from birth to 13 years of age of both sexes. The oral examinations were performed at the Pediatric AIDS Outpatient Clinic, São Lucas Hospital and Clinic Hospital, both in Porto Alegre, Brazil and at the School of Dental Medicine, University Hospital Center, State University of New York at Stony Brook, USA. The aim of this study was to identify the presence of viral infections in the oral cavity. PCR technique was used to determine opportunistic viral infections caused by CMV, EBV, and HSV in mucosal swabs. A high frequency of viral infection was detected in the oral cavity of HIV-infected children determined by the PCR technique. HIV-infected children with viruses had a favorable CD4+ T lymphocyte count and unfavorable viral load.

AIDS-Related Opportunistic Infections↗

[Influenza vaccination in HIV infected children: immunologic and viral load changes].

OBJECTIVE: To identify whether influenza immunization in HIV infected children could increase HIV viral load and decrease CD4+ lymphocytes count as a consequence of the response induced by a T cell-dependent antigen. METHODS: Prospective, descriptive study, with 51 HIV infected children, vaccinated against influenza in 1999, in Florianópolis, Brazil. Blood samples were collected at three different moments: on the immunization day; between 14 and 20 days later; between 60 and 90 days later. Plasma levels of HIV viral load and CD4+ lymphocytes count were determined. Friedman ANOVA test, Student t test for dependent samples, Bonferroni correction and Wilcoxon matched test were performed for statistical analysis. RESULTS: Children's mean age was 6.08 years (1 to 12.9 years). The medians of CD4+ lymphocyte count on vaccination day and at the other two moments were 789, 645 and 768 cells/mm(3), respectively. A significant reduction was observed in the CD4+ lymphocyte count between the first and the second analyses, but the same did not happen between the first and the third analyses. There was no significant difference of CD4+ lymphocyte percentage between the first and the second analyses. The median of HIV viral load values in log10 copies/ml was 4.38, 4.30 and 4.25, at the three moments respectively. Eight out of 44 patients (18.2%) showed increase > or =0.5 log 10 copies/ml in HIV viral load between the first and the second analysis and among these, four returned to levels close to their base levels in the third analysis. CONCLUSIONS: There was no significant change in the CD4+ lymphocyte percentage, in spite of a transitory increase in HIV viral load after influenza vaccination. Caution should be used when administering vaccine against flu to children with no stable clinical and immunological conditions, mainly if they are not under effective anti-retroviral therapeutics.

CD4 Lymphocyte Count↗

Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort.

BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.

Adult↗

Schistocytosis and a thrombotic microangiopathy-like syndrome in hospitalized HIV-infected patients.

Approximately 150 human immunodeficiency virus (HIV)-infected patients with a thrombotic microangiopathy (TMA)-like syndrome have been reported in the literature since the early 1980s. The prevalence of a TMA-like syndrome in our hospitalized patients was determined to discern whether it is a more common occurrence than previously recognized and, if possible, to delineate risk factors for its occurrence. A total of 350 patients admitted consecutively to the Johns Hopkins Hospital HIV inpatient service were assessed from May 1, 1996 through February 1, 1997. These patients were evaluated for the presence of anemia, thrombocytopenia, fragmented erythrocytes on peripheral blood smear (schistocytosis), renal dysfunction, neurologic dysfunction, and fever. The association of a TMA-like syndrome with demographic and clinical factors was analyzed. Schistocytosis was present in 24% of the patients and a TMA-like syndrome (anemia, thrombocytopenia, schistocytosis + renal dysfunction or neurologic dysfunction, and fever) was present in 7% of the patients. The patients who had a TMA-like syndrome were more likely to have a low CD4 lymphocyte count or CD4 percentage, Centers for Disease Control and Prevention stage C disease, and have bacterial sepsis. Age, race, HIV risk group, other diagnoses, and prescribed drugs were not associated. Patients were more likely to die if they had a TMA-like syndrome, independently of level of immunosuppression. Schistocytosis and a TMA-like syndrome are relatively common in hospitalized HIV-infected patients. This syndrome may contribute to mortality and morbidity, particularly in patients with more advanced disease.

Adult↗

Hodgkin's disease associated with human immunodeficiency virus infection. A clinical study of 46 cases. Cooperative Study Group of Malignancies Associated with HIV Infection of Madrid.

BACKGROUND: Hogdkin's disease is not an acquired immunodeficiency syndrome (AIDS)-defining illness. However, Hodgkin's disease associated with human immunodeficiency virus (HIV) infection has a different natural history and therapeutic outcome than in the general population of Hodgkin's disease patients. METHODS: The authors studied the epidemiologic and clinicopathologic features and therapeutic outcomes of 46 patients with Hodgkin's disease associated with HIV infection collected from a cooperative study of nine hospitals in Madrid, Spain. RESULTS: Forty-three (93.5%) of the subjects were men and three (6.5%) were women, with a mean age of 26.9 years. Thirty-nine (84.8%) were intravenous drug users and four (8.7%) were homosexuals. In 43 patients (93.5%), Hodgkin's disease was the first manifestation of HIV infection. In 16 patients (34.8%), AIDS developed after the diagnosis of Hodgkin's disease. Histologic subtypes were mixed cellularity (41.3%), lymphoid depletion (21.7%), nodular sclerosis (21.7%), and lymphocytic predominance (4.3%). At diagnosis, 89.1% had advanced stages (III,IV), 82.6% had B symptoms, and 41.3% had bone marrow involvement. Of 27 evaluable patients treated with chemotherapy, 44.4% had a complete response (16.7% relapsed) and 37% had a partial response. Median survival was 15 months (range, 1-44 months). Projected 3-year survival rate was 19%, and projected event-free survival rate was 22% at 30 months. Adverse prognostic factors for survival in univariate analysis were B symptoms, no response to chemotherapy, hemoglobin levels less than 11 g/dl, leukocyte count less than 4500/mm3, total lymphocyte count less than 1000/mm3, CD4 lymphocyte count less than 200/mm3, and alkaline phosphatase level greater than 300 IU/l. CONCLUSIONS: Hodgkin's disease associated with HIV infection is more frequent among intravenous drug addicts, and the clinical course is different in these patients from that in the general population of Hodgkin's disease patients, showing high frequency of advanced stages, unfavorable histologic subtypes, poor therapeutic response, and short survival time.

AIDS-Related Opportunistic Infections↗

Prognostic indicators for the development of AIDS in HIV antibody positive haemophiliac patients: results of a three-year longitudinal study.

In February 1986, 40 out of 75 adult patients with haemophilia A attending St. James's University Hospital were human immunodeficiency virus (HIV) antibody positive. Over a three-year period these patients were prospectively studied with regard to possible prognostic indicators for the development of the acquired immune deficiency syndrome (AIDS). Using the Centres for Disease Control (CDC) classification of HIV infection, 17 patients (42.5%) developed group 4 disease during this time, giving an actuarial three-year progression rate of 44%, and 5 patients (12.5%) died. The following parameters measured at recruitment were found independently to predict progression to AIDS: a serum beta 2-m level of greater than 3.5 mg/l, (chi 2 = 15.95, P less than 0.001), a serum IgA level of greater than 4.5 milligram(s) (chi 2 = 6.08, P less than 0.02) and p24 antigenaemia (chi 2 = 5.7, P less than 0.05). The actuarial three-year progression rate in those patients abnormal by two or more of these parameters was 100% (n = 7), compared to only 7% in patients who were normal by all three values (n = 15). CD4+ lymphocyte counts and CD4+:CD8+ ratios were significantly lower in HIV positive compared with HIV negative patients (P less than 0.01), but did not predict the development of AIDS.

Acquired Immunodeficiency Syndrome↗

Can immune markers predict subsequent discordance between immunologic and virologic responses to antiretroviral therapy? Adult AIDS Clinical Trials Group.

It is unclear why discordant immunologic and virologic responses occur during therapy for human immunodeficiency virus (HIV) infection. This study examined whether markers of immune activation and naive/memory lymphocyte subsets at study baseline could predict discordance between HIV type 1 (HIV-1) RNA and CD4+ lymphocyte responses at week 24 of antiretroviral therapy. Ten diverse, prospective antiretroviral studies with 1007 evaluable subjects were included. Subsets of subjects at increased risk for discordance were identified by recursive partitioning. The strongest predictor of more-favorable immunologic than virologic responses was a lower baseline CD4+ lymphocyte count. Weaker predictors in small subsets of subjects were fewer activated CD4+ lymphocytes and fewer CD8+ lymphocytes. Conversely, the strongest predictors of more-favorable virologic than immunologic responses were higher baseline CD4+ lymphocyte count and percentage. Additional predictors in some analyses were higher CD8+ lymphocyte count or percentage and lower HIV-1 RNA concentrations. Baseline markers of immune activation and naive/memory lymphocyte subsets had limited ability to predict subsequent discordance.

Acquired Immunodeficiency Syndrome↗

Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.

PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

AIDS-Related Opportunistic Infections↗

Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. EuroSIDA Study Group.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved rates of CD4-lymphocyte recovery and decreased the incidence of HIV-1-related morbidity and mortality. We assessed whether prophylaxis against Pneumocystis carinii pneumonia (PCP) can be safely discontinued after HAART is started. METHODS: We investigated 7333 HIV-1-infected patients already enrolled in EuroSIDA, a continuing prospective observational cohort study in 52 centres across Europe and Israel. We did a person-years analysis of the rate of discontinuation of PCP prophylaxis and of the incidence of PCP after the introduction of HAART into clinical practice from July, 1996. FINDINGS: The rate of discontinuation of primary and secondary PCP prophylaxis increased up to 21.9 discontinuations per 100 person-years of follow-up after March, 1998. 378 patients discontinued primary (319) or secondary (59) prophylaxis a median of 10 months after starting HAART. At discontinuation for primary and secondary prophylaxis, respectively, the median CD4-lymphocyte counts were 274 cells/microL and 270 cells/microL, the median plasma HIV-1 RNA load 500 copies/mL, and the median lowest recorded CD4-lymphocyte counts 123 cells/microL and 60 cells/microL. During 247 person-years of follow-up, no patient developed PCP (incidence density 0 [95% CI 0-1.5]). INTERPRETATION: The risk of PCP after stopping primary prophylaxis, especially in patients on HAART with a rise in CD4-lymphocyte count to more than 200 cells/microL, is sufficiently low to warrant discontinuation of primary PCP prophylaxis. Longer follow-up is needed to confirm a similarly low risk for stopping secondary PCP prophylaxis.

AIDS-Related Opportunistic Infections↗