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[CD8 hyperlymphocytosis syndrome and human immunodeficiency virus infection: 5 cases].

A retrospective study on 202 consecutive patients with HIV infection was reviewed. A particular syndrome with blood CD8 lymphocytosis > 1 500/mm3, associated with a diffuse lymphocytic infiltrate histologically proved in the tissue of different organs was present in five patients. Clinical findings were variable, depending on the location of visceral infiltrate by activated, polyclonal lymphocytes of CD8 phenotype: interstitial pneumonia (n = 3), parotid gland enlargement with sicca syndrome (n = 2), pseudo-tumoral splenomegaly (n = 1), peripheral neuropathy (n = 1), superficial generalized lymphadenopathy (n = 5). This syndrome occurred early during HIV infection. All patients had a blood CD4 lymphocyte count > 200/mm3. This disorder is a host immune response, sometimes associated with the presence of some HLA antigens: HLA-DR5 or HLA A1 B8 DR3. Whether this immune response is specific or not, whether outcome of HIV infection depends on hyper CD8 lymphocytosis remains to be proved.

Adult↗

[The pitfalls of lymphocyte immunophenotyping during HIV infection].

Preferential infection of CD4+ lymphocytes by HIV, related to both direct and indirect mechanisms, leads to progressive decrease in this population. A CD4 lymphocyte count has become the preferential test for monitoring the infection. Thus, a flow cytometry laboratory handles a great number of phenotyping prescriptions that require accuracy and precision. The technical and biological parameters involved are listed, and some rules for interpretation of results given. Because no standardization exists and because cytometers are not automated, there is often great variability between laboratory results. We show that variability can be decreased by the use of correct procedures for analysis on the cytometer (especially for fluorescence interpretation). On the other hand, many biological factors have a significant effect on the results. A list of these factors is given: circadian rhythm, other infectious diseases and drugs. Lastly, the distribution of values in normal subjects is reported. The wide range shows that results from a patient must be compared with previous values to determine the course of the infection. These data would help in defining and interpreting results.

Adult↗

[Progressive multifocal leukoencephalopathy in patients with AIDS: is there a change in patients treated with highly active antiretroviral therapies?].

AIMS: Progressive multifocal leukoencephalopathy (PML) develops in up to 4-8% of all AIDS patients. Before highly active antiretroviral therapies (HAART) the median survival was only 4-6 months. In this study we analyzed epidemiological parameters in AIDS-related LMP patients in search for differences in the incidence and prognosis between before and after HAART era. METHODS: Retrospective review of clinical histories of patients diagnosed of AIDS and PML at Hospital Meixoeiro in Vigo, Spain, between 01/01/94-31/05/97 (Before-HAART period) and 01/06/97-30/04/00 (After-HAART period). PML was diagnosed by clinical and neuroimaging criteria, with biopsy in 2 cases and positive JC virus hibridation in CSF in another case. RESULTS: We identified 12 patients (global prevalence of 3.8%, without differences between periods): 11 males, 10 intravenous drugs users (IDU), mean age of 38 years (31-43). In 6, LMP was the first opportunistic infection. When PML was diagnosed, 6 patients had a HIV viral load (VL) > 250.000 copies of RNA/ml (range, 254.003-3.170.000), and overall a mean CD4 lymphocytes counts of 89 x 10(6)/ml (40-134). Three patients received cytarabine + Interferon with zidovudine (2 patients) and zidovudine + lamivudine (1 patient) and other patient HAART + cidofovir, but no improvement was observed. The median survival was 10 months in before-HAART group and 17 months in after-HAART group, with a survival > 48 months in 2 patients in the last group. CONCLUSIONS: LMP is observed in severely immunosuppressed IDU men (VL > log 5 copies RNA/ml and CD4 < 150 x 106/ml). Complementary treatments were ineffective and only in patients with HAART a prolonged survival was observed.

Acquired Immunodeficiency Syndrome↗

Bacterial bronchitis and bronchiectasis in human immunodeficiency virus infection.

BACKGROUND: Bacterial pneumonia and sinusitis are important causes of morbidity in patients with human immunodeficiency virus (HIV) infection. We noted an increased incidence of bacterial bronchitis and bronchiectasis in our patients with HIV infection. METHODS: This study was conducted on persons with HIV infection at a county hospital and clinic. Bronchiectasis was diagnosed by bronchogram and computed tomography in one patient and by computed tomography alone in two others. Bacterial bronchitis was defined by a Gram's stain showing an abundance of neutrophils with a predominance of one or more bacteria and by a confirmatory sputum culture. Bronchoscopy with broncho-alveolar lavage was performed in patients with bronchitis to eliminate other causes of bronchial inflammation. RESULTS: Eighteen episodes of bacterial bronchitis in 10 patients are described. The mean CD4 lymphocyte counts for these patients was 0.061 x 10(9)/L (range, 0.001 to 0.203 x 10(9)/L). The most common pathogens in 18 episodes of bacterial bronchitis were Haemophilus influenzae and Streptococcus pneumoniae (five episodes each) and Pseudomonas aeruginosa (four episodes). Response to antibiotic therapy was usually rewarding though recurrences were frequent. Three patients with well-defined bronchiectasis who appeared to have developed, or who became symptomatic during the course of, HIV infection are described. Their mean CD4 cell count was 0.03 x 10(9)/L (range, 0.024 to 0.037 x 10(9)/L). Haemophilus influenzae, Staphylococcus aureus, Pseudomonas cepacia, and P aeruginosa were recovered from these patients; the P aeruginosa was a mucoid strain. CONCLUSIONS: Recurrent bacterial bronchitis should be added to the list of bacterial infections that occur with increased frequency with HIV infection. Repeated bacterial bronchitis may lead to bronchiectasis, which may be more common in HIV infection than generally appreciated.

Adult↗

Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men.

The authors sought to determine if different levels of dietary intake of micronutrients are associated with the progression of human immunodeficiency virus type 1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). A total of 281 HIV-1 seropositive homosexual/bisexual men were seen semiannually since 1984 at the Baltimore/Washington, DC site of the Multicenter AIDS Cohort Study. Participants completed a self-administered semiquantitative food frequency questionnaire at baseline. Levels of daily micronutrient intake at baseline were examined in relation to subsequent progression to AIDS (1987 Centers for Disease Control definition; n = 108) during a median follow-up period of 6.8 years. For each nutrient, the authors used a Cox proportional hazards model to adjust for age, presence of symptoms, CD4+ lymphocyte count, energy intake, use of antiretrovirals, and use of Pneumocystis carinii pneumonia prophylaxis. The highest levels of total intake (from food and supplements) of vitamins C and B1 and niacin were associated with a significantly decreased progression rate to AIDS: vitamin C (relative hazard (RH) = 0.55, 95% confidence interval (CI) 0.34-0.91), vitamin B1 (RH = 0.60, 95% CI 0.36-0.98), and niacin (RH = 0.52, 95% CI 0.31-0.86). The relation between total vitamin A intake and progression to AIDS appeared to be U-shaped; the lowest and highest quartiles of intake did most poorly, while the middle two quartiles were associated with significantly slower progression to AIDS (RH = 0.55, 95% CI 0.35-0.88). Increased intake of zinc was monotonically and significantly associated with an increased risk of progression to AIDS (for highest vs. lowest quartiles, RH = 2.06, 95% CI 1.16-3.64). In a final multinutrient model, vitamin A, niacin, and zinc remained significantly associated with progression to AIDS, while vitamin C was only marginally significant.

Acquired Immunodeficiency Syndrome↗

Decreased antioxidant defence in individuals infected by the human immunodeficiency virus.

BACKGROUND: The oxidative stress associated with HIV infection may be important for the progression of the disease because reactive oxygen species activate the nuclear transcription factor NF-kappaB, which is obligatory for HIV replication. PATIENTS AND METHODS: The activities of the antioxidant enzymes superoxide dismutase (SOD, EC 1.15.1.1) and glutathione peroxidase (GPx, EC 1.11.1.9) of blood plasma and peripheral blood mononuclear cells, as well as the plasma levels of ascorbate, alpha-tocopherol and beta-carotene, were measured in 75 subjects with HIV infection and in 26 controls. The HIV-infected patients were classified according to the Walter Reed Army Institute criteria. RESULTS: The extracellular SOD (EC-SOD) of blood plasma activity was decreased in HIV-infected patients compared to controls, while the SOD activity of mononuclear cells decreased with the HIV-associated disease progression. GPx activities and alpha-tocopherol concentration of HIV-infected patients neither differed as compared to controls nor in relation to disease progression. Lower concentrations of ascorbate and beta-carotene were found in HIV-infected patients than in controls. A positive correlation between CD4 lymphocyte counts and the SOD activities of plasma and mononuclear cells was found. CONCLUSION: These results suggest that abnormalities of antioxidant defence, mainly of SOD activity, are related to the progression of the HIV infection.

Adult↗

High rates of transmission of subtype E human immunodeficiency virus type 1 among heterosexual couples in Northern Thailand: role of sexually transmitted diseases and immune compromise.

The heterosexual transmission of subtype E human immunodeficiency virus type 1 (HIV-1) infection was evaluated in 467 couples in Thailand in whom the man was HIV-1 positive and the woman had no risk factors for HIV other than sex with her infected partner. At baseline, 216 (46.3%) of the 467 women were positive for HIV-1; prevalence of HIV among women was 52.2% when their male partners had CD4+ lymphocyte counts of <200 cells/microL, 45.9% in women whose partners had counts of 200-499 micro/L, and 39.2% in women whose partners had counts of >/=500/microL. Women were twice as likely to be HIV positive if their partners had a history of a sexually transmitted disease (STD); however, their HIV prevalence was 29% among couples who had no STD history. It appears that female partners of men infected with subtype E HIV-1 are at high risk of infection even when the man's CD4+ cell count is relatively high. A high rate of STDs may contribute significantly to this risk [corrected].

Blood Donors↗

Disseminated cutaneous histoplasmosis in patients infected with human immunodeficiency virus.

BACKGROUND: In the pre-AIDS era disseminated histoplasmosis was rare and the cutaneous manifestations thereof were reported infrequently. A range of unusual clinical manifestations of disseminated cutaneous histoplasmosis (DCH) in AIDS patients has been documented, but the cutaneous histopathological descriptions are short and incomplete. In addition, the histopathological spectrum of AIDS-associated DCH is poorly recognized. METHODS: This is a prospective 32-month study of all HIV positive patients diagnosed with histoplasmosis in the Departments of Anatomical Pathology and Dermatology, Nelson R. Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa. Clinical distribution and morphology of the individual skin lesions and CD4+ lymphocyte counts in the peripheral blood were analysed in relation to the histopathological features of biopsied lesional tissue. Ultrastructural examination of tissue retrieved from the wax blocks of three cases that exhibited dermal karyorrhexis and collagen necrosis was undertaken. Fungal culture of lesional skin tissue was undertaken in all patients. RESULTS: Twenty-one biopsies of papules (7), nodules (4), plaques (5), erythema multiforme-like lesions (2), vasculitic lesions (2) and exfoliative dermatitis (1) from 14 patients were examined. Of four biopsies (CD4 range: 120-128 cells/mm3) one and three demonstrated necrotizing and non-necrotizing granulomatous inflammation with a paucity of intrahistiocytic microorganisms. Seven biopsies (CD4 range: 2-56 cells/mm3) demonstrated diffuse dermal and intravascular accumulation of histiocytes densely parasitized by Histoplasma capsulatum var. capsulatum. Vasculitis, karyorrhexis or collagen necrosis was not present. Ten biopsies (CD4 range: 2-72 cells/mm3) demonstrated diffuse dermal karyorrhexis, collagen necrosis and interstitial, extracellular H. capsulatum var. capsulatum. Histiocytic disintegration and nuclear fragmentation and release of intact microorganisms and intact and ruptured lysosomes were identified ultrastructurally. Leucocytoclastic vasculitis was present in two biopsies of vasculitic clinical morphology. Microbiological culture confirmed histoplasmosis in all cases. Three patients died before treatment was commenced. Two patients died within the first two days of induction of therapy. Nine patients demonstrated dramatic healing of the cutaneous lesions. CONCLUSIONS: Despite the clinicopathological spectrum of DCH and the attendant host immunocompromise, timely and appropriate treatment of DCH may be lifesaving and allows rapid healing of skin lesions. A high index of clinical suspicion and skin biopsies and culture are crucial for accurate diagnosis.

Adult↗

Efficacy and safety of rechallenge with low-dose trimethoprim-sulphamethoxazole in previously hypersensitive HIV-infected patients.

OBJECTIVE: This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX. DESIGN: A prospective, open study. SETTING: A tertiary referral hospital. PATIENT: Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX. INTERVENTIONS: Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week). MAIN OUTCOME MEASURES: That rechallenge is more likely to be successful in those with advanced HIV disease. RESULTS: Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred. CONCLUSIONS: Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

AIDS-Related Opportunistic Infections↗

Herpes zoster in HIV-1-infected patients in the era of highly active antiretroviral therapy: a prospective observational study.

Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.

AIDS-Related Opportunistic Infections↗

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a relatively low baseline viral load. Furthermore, components of these protease inhibitor-sparing combinations such as didanosine or nevirapine are suitable for once daily administration.

Anti-HIV Agents↗

A controlled study of early neurologic abnormalities in men with asymptomatic human immunodeficiency virus infection.

BACKGROUND: Although neurologic complications are frequent in the acquired immunodeficiency syndrome, their incidence and progression in early human immunodeficiency virus (HIV) infection remain controversial. The goal of this study was to assess neurologic manifestations in asymptomatic carriers of HIV. METHODS: We studied 29 HIV-seropositive homosexual men and 33 seronegative homosexual controls by means of neurologic and neuropsychological examinations, magnetic resonance imaging (MRI), and electrophysiologic tests (electroencephalography, multimodal evoked-potential tests, and otoneurologic tests). After six to nine months, the tests were repeated in 27 seropositive men and 30 controls. The investigators were blind to the serologic status of the subjects. RESULTS: The seropositive subjects had a mean CD4+ lymphocyte count of 635 X 10(6) per liter. Neurologic and neuropsychological examination, MRI, and measurements of pattern visual evoked potentials did not show significant differences between the two groups. The latencies of the median-nerve somatosensory evoked potentials were slightly prolonged in the seropositive men. The initial electroencephalogram was judged abnormal in 8 of 27 of the seropositive subjects (30 percent) as compared with none of the controls, with a slowing of fundamental activity, anterior spread [corrected] of alpha rhythm, subnormal reactivity, and unusual anterior theta activities. These findings were confirmed by computerized spectral analysis. The second electroencephalogram was abnormal in 10 of 25 of the seropositive men (40 percent). The otoneurologic evaluation identified abnormalities in the central auditory or vestibulo-ocular pathways in 34 percent of the seropositive men (10 of 29), as compared with 6 percent of the controls (2 of 33), on the first examination and in 44 percent (12 of 27) and 7 percent (2 of 30), respectively, on the second examination. Altogether, electrophysiologic abnormalities were found in 67 percent of the seropositive men (18 of 27) and 10 percent of the controls (3 of 30) (P less than 0.00005). CONCLUSIONS: In persons with asymptomatic HIV infection, electrophysiologic tests may be the most sensitive indicators of subclinical neurologic impairment. Electrophysiologic abnormalities are far more common in asymptomatic carriers of HIV than in controls and tend to progress over time.

Adult↗

The use of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: impact on medical, palliative care, and quality of life outcomes.

The effect of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is usually measured by survival, CD4 lymphocyte counts, HIV-1 RNA viral load testing, and the occurrence of opportunistic infections. This pilot study sought to measure the impact of HAART treatments on a wide range of clinical outcomes and psychological variables in a sample of patients with advanced HIV infection. Seventy patients with advanced AIDS who were protease inhibitor naïve were started on HAART regimens. Patients were admitted to an AIDS inpatient unit of a long-term care facility that provides treatment and palliative care. All patients were diagnosed with AIDS, had CD4 cell counts below 300/cc(3), and had a projected survival of greater than one month. Patients were started on triple-drug HAART regimens with daily medical supervision and observation. In addition to standard clinical and laboratory markers, a series of observer-rated and self-report instruments were used to measure various physical and psychological factors (e.g., pain and symptom distress, psychological well-being, depression). Data were collected at baseline and after 1 and 3 months of HAART therapy. As expected, the CD4 count increased and viral load levels decreased significantly over the 3-month study period. In addition, patients improved significantly in body weight, and serum albumin and ferritin levels. The only psychosocial measure that improved significantly with treatment was depression. Ratings of pain intensity, physical and psychological symptom distress, and overall quality of life did not change. Of the 70 patients studied, 84.3% were still alive after the 3-month study period. Of these, 6 (8.6%) were discharged to community. However, 17 surviving patients (24.3%) had HAART regimens discontinued due to drug intolerance and 11 patients (15.7%) expired during the study period. While these data are preliminary, HAART regimens appear to have positive effects on CD4 count, HIV viral load, and several other measures of physical well-being in patients with advanced AIDS. Despite these improvements, the benefits of treatment on pain and symptom distress, and psychological well-being were less clear. In addition, treatment failure (mortality and intolerance) were not uncommon in this sample (40%). Further research is clearly necessary to better understand the benefits of HAART therapy in patients with advanced HIV infection.

Adult↗

HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda.

In order to study the relation between human immunodeficiency virus (HIV) infection and malaria in women, during and after pregnancy, a prospective cohort study was initiated at the Centre Hospitalier de Kigali in Rwanda through routine voluntary and confidential HIV screening in antenatal clinics. At inclusion in the cohort of all HIV-positive and an equivalent number of HIV-negative pregnant women, between 21 and 28 weeks of gestation, sociodemographic characteristics and medical history during the current pregnancy were collected; screening for malaria (tick blood smear) and anemia and a CD4 lymphocyte count were systematically performed. Each woman enrolled had a monthly follow-up until 6 months after delivery. A clinic was implemented that was accessible and free of charge to every woman during the study period between scheduled visits. Malaria infection was systematically screened in case of fever or other compatible symptoms. The cohort included 228 HIV-positive and 229 HIV-negative women. At inclusion, malaria prevalence was 8.0% in HIV-positive women and 3.5% in HIV-negative women (P < 0.04). Over the study period, the incidence of malaria was 6.2 per 100 women-months in the HIV-positive group and 3.5 in the HIV-negative group (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.4-2.3). The bulk of the difference occurred postpartum. The Kaplan-Meier 9-month probability of remaining free of malaria infection was 51.8% in HIV-positive women and 65.2% in HIV-negative women (P = 0.013). When taking account in the same multivariate model (including HIV infection, primiparity, CD4 lymphocytes, anemia, and education level), positive HIV serostatus remained the only factor significantly associated with malaria infection (RR = 1.4, CI = 1.1-1.6; P = 0.016). Our study prospectively documents the association between malaria and maternal HIV infection and highlights the increased risk of malaria occurrence in all HIV-infected women. Strategies to reduce the malaria morbidity during pregnancy should be reinforced in areas of high HIV seroprevalence.

Adult↗

Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma.

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effectiveness of highly active antiretroviral therapy among HIV-1 infected women.

STUDY OBJECTIVE: To describe the impact of highly active antiretroviral therapy (HAART) on mortality, morbidity, and markers of HIV disease progression in HIV infected women. DESIGN: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. SETTING: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). PARTICIPANTS: A total of 1691 HIV seropositive women with a study visit after April 1996. MAIN RESULTS: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. CONCLUSIONS: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality.

Adolescent↗

Successful treatment with cyclosporine and high-dose gamma immunoglobulin for persistent parvovirus B19 infection in a patient with refractory autoimmune hemolytic anemia.

We describe a patient with persistent pure red cell aplasia due to human parvovirus B19 (HPVB19) infection during immunosuppressive therapy for refractory autoimmune hemolytic anemia (AIHA). The patient had been given corticosteroid (CS) and/or azathioprine for AIHA. During the course of treatment, reticulocyte count and hemoglobin levels decreased suddenly. Bone marrow aspirate showed erythroid lineage-specific aplasia with a few giant proerythroblasts, suggesting the presence of HPVB19 infection. The diagnosis of aplastic crisis due to HPVB19 infection was based on positive test results by polymerase chain reaction for HPVB19 immunoglobulin M (IgM) antibody and B19 DNA. Although splenectomy followed by administration of high-dose gamma globulin (HDIG) and plasma exchange were performed, the crisis and hemolysis recurred. Aplastic crises occurred several times when the B19 IgG result became negative and the CD4+ lymphocyte count was less than 300/microL. The patient showed complete recovery from anemia after CS was switched to cyclosporin A (CsA) and intermittent administration of HDIG. The result for B19 IgG antibody was continuously positive, and the DNA result became negative after these treatments. The results in this case indicated that concomitant administration of CsA and intermittent administration of HDIG can lead to cure of chronic anemia due to HPVB19 infection in patients with refractory AIHA.

Adult↗

[Focal mycobacterial lymphadenitis after starting highly active antiretroviral therapy].

HISTORY AND FINDINGS: A 30-year-old man with a known HIV infection for 7 years presented for treatment with antiretroviral drugs. He was known to have had herpes zoster, oral hairy leukoplakia and recurrent Candida stomatitis, but was otherwise without symptoms. INVESTIGATIONS: The CD4 lymphocyte count was 19 cells/mm3 and there were 41,000 HIV-RNA copies/ml. DIAGNOSIS, TREATMENT AND COURSE: The HIV infection was in CDC stage B3, indicating the need for combined antiretroviral treatment. A week after starting stavudine, saquinavir and ritonavir he had to be admitted because of nausea and vomiting, colicky abdominal pain, diarrhea, fever up to 39 degrees C and a rise of C-reactive protein to 207 mg/dl. Bacteriological examination of feces and biopsy of an enlarged retroperitoneal lymph node revealed atypical mycobacteria. Antituberculosis treatment was started. The CD4 cell count rose to 56/mm3 and the viral count fell to 11,000/ml. Each time after initiating a different antiviral regimen the symptoms recurred. CONCLUSIONS: This case illustrates an atypical manifestation of on opportunistic infection: during combined antiviral treatment the CD4 cell count rose and thus precipitated an heretofore subclinical mycobacterial infection with focal lymphadenitis. If, on starting antiretroviral treatment at a late HIV stage, new symptoms develop within 1-3 weeks, one should consider drug-induced side effects or the onset of an opportunistic infection that has become manifest as the result of an improved immunological state.

AIDS-Related Opportunistic Infections↗