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PubMed1998

Phase II trial of liposomal daunorubicin in the treatment of AIDS-related pulmonary Kaposi's sarcoma.

PURPOSE: Kaposi's sarcoma (KS) is the most common tumor in patients with AIDS and can be fatal in patients with lung involvement. Systemic chemotherapy is the most effective treatment for pulmonary KS. We thus conducted this study to determine the efficacy of liposomal daunorubicin in the treatment of patients with pulmonary KS. METHODS: Patients with biopsy-proven, symptomatic pulmonary KS were accrued. Liposomal daunorubicin was given at a dose of 60 mg/m2 intravenously every 2 weeks. Response was monitored by chest radiographs, pulmonary function tests, arterial blood gases, and grading of pulmonary symptoms. RESULTS: Fifty-three male patients were accrued. The median CD4+ lymphocyte count was 13/microL (range, 0 to 200); 70% reported a prior AIDS-defining opportunistic infection. All patients were symptomatic, with cough reported in all patients, shortness of breath in 94%, and hemoptysis in 55%. The mean study entry diffusing capacity of carbon monoxide (DLCO) was 58.5% (percent of predicted). The median dose of liposomal daunorubicin delivered was 360 mg/m2 (range, 60 to 1,380). More than 75% of patients had complete or partial resolution of baseline pulmonary symptoms. Complete or partial improvement in DLCO was observed in 22%; complete or partial resolution of radiographic abnormalities was reported in 32%. The most common treatment-related toxicity was neutropenia, which occurred in 85%. There were no instances of cardiac toxicity observed, even at high cumulative doses. CONCLUSION: Liposomal daunorubicin at 60 mg/m2 is safe and active in patients with pulmonary KS. Trials combining liposomal daunorubicin with other active agents in KS should be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma.

PURPOSE: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. MATERIALS AND METHODS: A regimen of paclitaxel at a dose of 100 mg/m(2) was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. RESULTS: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4(+) lymphocyte count was 20 cells/mm(3) (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. CONCLUSION: Paclitaxel at 100 mg/m(2) given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection.

The purpose of this parallel treatment group, double-blind, multicenter study was to characterize the pharmacokinetics of nevirapine and lamivudine when coadministered to patients with the HIV-1 infection. This pharmacokinetic interaction study was nested within a larger Phase III clinical trial conducted to characterize the safety and efficacy of coadministered nevirapine and lamivudine. One hundred HIV-1 infected patients with CD4+ lymphocyte counts < 200 cells/mm3and who were on a background of nucleoside (zidovudine [ZDV], didanosine [ddI], zalcitabine [ddC], stavudine [d4T]) therapy were randomly assigned to be treated with either nucleoside + lamivudine + nevirapine or nucleoside + lamivudine + placebo. Each patient underwent blood sampling at defined times for the purpose of determining the concentration of nevirapine in plasma and lamivudine in serum under steady-state conditions. Each patient was also monitored closely for concomitant administration of other drugs, including ZDV, ddI, ddC, d4T and cotrimoxazole. The pharmacokinetics of nevirapine and lamivudine were characterized using nonlinear mixed-effects modeling. There were no reported serious adverse events during the 40-day pharmacokinetic study. The results of the modeling analysis revealed that nevirapine had no effect on the pharmacokinetics of lamivudine. Estimates of the apparent clearance for nevirapine (CL/F = 3.3 L/hour; 95% confidence interval [CI] 2.9 to 3.7 L/hour) and lamivudine (CL/F 27.6 L/hour; 95% CI 22 to 33.2 L/hour) were consistent with the values reported in earlier trials. However, the results also showed that concomitant administration of lamivudine with cotrimoxazole resulted in a 31% reduction in the apparent clearance of lamivudine, resulting in a 43% increase in the average steady-state lamivudine serum concentrations. These results indicate that chronic concurrent administration of cotrimoxazole with lamivudine may significantly affect the steady-state pharmacokinetics of lamivudine.

Adult↗
PubMed1998

Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis.

The serum level of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D], the biologically most potent metabolite of vitamin D, is tightly regulated within narrow limits in human healthy adults. 1,25-(OH)2D deficiency is rare and is associated with disturbances in calcium and bone metabolism. We have previously reported a marked decrease in serum levels of 1,25-(OH)2D in human immunodeficiency virus (HIV)-infected patients. The present study was designed to further examine the causes and consequences of severe 1,25-(OH)2D deficiency in these patients. The design was a prospective cohort study. Fifty-four HIV-infected patients clinically classified according to the revised criteria from Centers for Disease Control and Prevention and healthy controls were studied. Parameters related to vitamin D and calcium metabolism as well as immunological and nutritional status were determined. Twenty-nine of the patients (54%) had serum levels of 1,25-(OH)2D below the lower reference limit, and 18 of these had undetectable levels. In contrast, HIV-infected patients had normal serum levels of 25-hydroxyvitamin D and vitamin D-binding protein. HIV-infected patients as a group had modestly depressed serum calcium and PTH levels. There were, however, no correlations between these parameters and serum levels of 1,25-(OH)2D. There were no differences in serum calcium or PTH levels or nutritional status when patients with severe 1,25-(OH)2D deficiency were compared to other patients, but patients with undetectable 1,25-(OH)2D had significantly elevated serum phosphate levels. Furthermore, patients with undetectable 1,25-(OH)2D levels were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor necrosis factor-alpha (TNFalpha). We conclude that inadequate 1alpha-hydroxylation of 25-hydroxyvitamin D seems to be the most likely cause of 1,25-(OH)2D deficiency in HIV-infected patients, possibly induced by an inhibitory effect of TNFalpha. The low 1,25-(OH)2D and high TNFalpha levels observed may impair the immune response in HIV-infected patients both independently and in combination and may represent an important feature of the pathogenesis of HIV-related immunodeficiency. Markedly depressed 1,25-(OH)2D serum levels are also present in certain other disorders characterized by immunological hyperactivity. Thus, the findings in the present study may not only represent a previously unrecognized immune-mediated mechanism for induction of 1,25-(OH)2D deficiency in human disease, but may also reflect the importance of adequate serum levels of 1,25-(OH)2D for satisfactory performance of the immune system in man.

Adolescent↗
PubMed2002

A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.

BACKGROUND: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. OBJECTIVE: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. METHODS: Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. RESULTS: The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. CONCLUSIONS: CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.

AIDS Dementia Complex↗
PubMed1993

Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study.

We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7%. Overall, 15% of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl; p = 0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/m2; p = 0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p = 0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p = 0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4+ lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1% of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease.

AIDS Dementia Complex↗
PubMed1998

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1999

JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy.

OBJECTIVE: To determine the clinical value of JC virus (JCV) detection in various anatomic compartments for the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: CSF, peripheral blood mononuclear cells (PBMC), plasma, and urine samples were evaluated from HIV-infected and uninfected individuals. JCV DNA was detected by PCR and was quantified using a competitive PCR ELISA. RESULTS: JCV DNA was detected in one-third of the urine samples, regardless of HIV serostatus or clinical evidence of PML. JCV DNA was detected in five of eight PBMC and three of seven plasma samples of HIV-positive PML patients, in 13 of 103 PBMC and 7 of 32 plasma samples of HIV-positive persons without PML, but in 0 of 18 PBMC and 0 of 13 plasma samples of HIV-negative control subjects. There was no correlation between the presence of JCV DNA in the PBMC and plasma, but the detection of JCV in either compartment was associated with low CD4+ lymphocyte counts. JCV DNA was not detected in the CSF of 27 of 27 HIV-negative persons and 64 of 65 HIV-positive persons without PML, but was found in the CSF of three of three HIV-negative immunosuppressed individuals and 10 of 11 HIV-positive individuals with clinical and radiologic evidence of PML, confirmed by biopsy in four of four tested patients. PBMC harbored 10 to 90 JCV copies/microg DNA, and the CSF of the PML patients contained 3.65 x 10(4) to 2.04 x 10(5) JCV copies/mL CSF. CONCLUSIONS: JCV viruria was found as frequently in HIV-positive individuals as in control subjects, suggesting that its detection has no clinical value. JCV detection in the blood correlates with immunosuppression and not with PML. The presence of JCV in the CSF is highly sensitive and specific for PML, and a high CSF JC viral load was associated with poor clinical outcome in patients receiving antiretroviral therapy. JCV quantification in the CSF constitutes a potentially important tool for monitoring clinical PML treatment trials.

Case-Control Studies↗
PubMed1999

Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.

OBJECTIVE: To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. BACKGROUND: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (1H MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved 1H MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. METHODS: Two-dimensional 1H MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. RESULTS: Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. CONCLUSIONS: 1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.

Adult↗
PubMed2000

AIDS-related focal brain lesions in the era of highly active antiretroviral therapy.

OBJECTIVE: To compare the years since the introduction of highly active antiretroviral therapy (HAART) with the pre-HAART era for trends in the proportions of HIV-related focal brain lesion-causing disorders. METHODS: A prospective, single-center study of all consecutive HIV-infected patients with a neurologic presentation and focal brain lesions observed between January 1991 and December 1998 was undertaken. RESULTS: The major diagnoses in the 281 patients were toxoplasmic encephalitis (36.4%), primary CNS lymphoma (26.7%), progressive multifocal leukoencephalopathy (18.2%), and focal HIV encephalopathy (5.0%). During the HAART period, patients were less likely to be male, contracted HIV more often through heterosexual exposure, had fewer previous AIDS-defining events, received antiToxoplasma prophylaxis less frequently, had a CD4+ lymphocyte count 2.5 times higher, and had diagnosis based more often on PCR assays from CSF, reducing the need for brain biopsy and enhancing the likelihood of in vivo diagnosis. Using all patients hospitalized per year as reference population, the risk of focal brain lesions strongly increased during the pre-HAART period and declined significantly during the HAART years. In the HAART period a relevant decline of primary CNS lymphoma was found (OR for 1998, 0.25; p for trend = 0.03) and the effect of progressive calendar year was confirmed on multivariable analysis (OR, 0.52; 95% CI, 0.28 to 0.97). The frequency of toxoplasmic encephalitis decreased during the pre-HAART era and was stable afterwards. For progressive multifocal leukoencephalopathy, a slight increase was seen over time. Focal white matter lesions without enhancement or mass effect increased between 1991 and 1998. CONCLUSIONS: During the HAART era, AIDS-related primary CNS lymphoma showed a strong decline, toxoplasmic encephalitis remained stable, and progressive multifocal leukoencephalopathy showed a slight increase. Focal white matter lesions without mass effect or contrast enhancement became the most frequently seen focal brain lesion. For differential diagnosis, PCR-based assays from CSF led to a shift from brain biopsy toward a minimally invasive approach with an augmented likelihood of in vivo diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Cutaneous cryptococcosis in two patients with acquired immunodeficiency syndrome.

We present 2 cases of systemic cryptococcosis with cutaneous involvement in patients with acquired immunodeficiency syndrome (AIDS). Both patients were male, intravenous drug abusers, 31 and 35 years old, with severe immunodepression and a CD4+ lymphocyte count of 10/ml and 1/ml, respectively. They both had papular lesions reminiscent of molluscum contagiosum and in one patient with concomitant systemic leishmaniasis, there were spores of Cryptococcus neoformans coexisting with the leishmanias in the cutaneous lesions, constituting the first reported case of this particular association. Both patients responded well to amphotericin B followed by fluconazole.

AIDS-Related Opportunistic Infections↗
PubMed2002

Risk factors and cumulative incidence of anaemia among HIV-infected injection drug users.

Risk factors for anaemia and cumulative incidence of anaemia were examined in a longitudinal cohort study of 622 injection drug users (IDUs) (8885 visits) in Baltimore, Maryland, from 1988 to 2000. At enrollment, 19.6% subjects were anaemic (16.1% of men and 30.5% of women, P<0.0001) and 8.4% had microcytic anaemia (6.7% of men and 14.0% of women, P=0.006). Cumulative incidence of anaemia was 82.2% (87.9% of men and 100% of women, P<0.0001) during a median of 7.5 years follow-up. Factors associated with anaemia included age (per 5 year increase, odds ratio (OR)=1.22; 95% confidence interval (CI): 1.10, 1.36), female gender (OR=1.62; 95% CI: 1.16, 2.27), CD4+ lymphocyte count <200 cells/microl (OR 1.85; 95% CI: 1.52, 2.24), weight loss (OR 1.55; 95% CI: 1.26, 1.91), oral thrush (OR 1.53; 95% CI: 1.21, 1.94), Mycobacterium avium complex infection (OR 1.30; 95% CI: 1.04, 1.64), and zidovudine use (OR 1.24; 95% CI: 1.04, 1.48). Higher body mass index (OR 0.92; 95% CI: 0.88, 0.95) and marijuana use (OR 0.75; 95% CI: 0.61, 0.92) were associated with a lower risk of anaemia. The cumulative incidence of anaemia is high among IDUs, and women are at highest risk of anaemia.

Adult↗
PubMed2003

Randomized trial of an adherence programme for clients with HIV.

Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy. The adherence package included an education programme, individualized planning of regimens, and the opportunity for a patient to choose from a number of adherence aids and reminder devices. A randomized step wedge design was used. Forty-three individuals were randomized to begin the intervention over a five-month period. There was a substantial fall in the number of missed doses reported for the last four days (0.76 to 0.38, P =0.03) and last seven days (1.5 to 0.74, P =0.005) but not for the last 28 days (2.5 to 2.5, P =0.63). There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention. The Morisky score during the pre and post intervention periods was significantly different (P =0.006), 2.9 (SD 0.9) and 3.3 (SD 0.8) respectively. This adherence package improved self reported adherence during the last four and seven days.

Adult↗
PubMed2005

Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient.

Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.

Adult↗
PubMed2006

An algorithmic approach to intracranial mass lesions in HIV/AIDS.

We developed a diagnostic and therapeutic algorithm for intracranial mass lesions in patients with HIV/AIDS that obviates the need for neurosurgical intervention. The approach is based upon CD4(+) lymphocyte count, serum toxoplasma immunoglobulin G (IgG) serology, chest X-ray, routine lumbar puncture studies, cerebrospinal fluid (CSF) cytology, CSF adenosine deaminase or Mycobacterium tuberculosis polymerase chain reaction testing, single positron emission-computed tomography (SPECT) scanning for intracranial enhancing lesions, and limited therapeutic trials. Over a 12-month period involving 26 patients, we found that the algorithm correctly identified the aetiology of focal intracranial lesions in all 23 evaluable patients. Costs for SPECT scanning for the entire study cohort were more than offset by the savings achieved by reduced hospital stays for the four patients with lymphoma alone. An algorithmic approach can accurately identify the cause(s) of central nervous system (CNS) mass lesions in HIV-infected patients, and SPECT scanning can replace stereotactic brain biopsy in most cases where opportunistic malignancy is suspected.

AIDS-Related Opportunistic Infections↗
PubMed2006

Prevalence and risk factors of squamous intraepithelial lesions of the cervix among HIV-infected women - a long-term follow-up study in a low-prevalence population.

HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.

Adolescent↗
PubMedDate not supplied

Nevirapine or efavirenz combined with two nucleoside reverse transcriptase inhibitors compared to HAART: a meta-analysis of randomized clinical trials.

PURPOSE: A meta-analysis of randomized controlled trials (RCTs) was performed to evaluate effectiveness and tolerability of triple antiretroviral therapy regimens in HIV-infected patients. METHOD: RCTs including the nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine (NVP) or efavirenz (EFV) compared to two nucleoside reverse transcriptase inhibitor (NRTI) regimens and to three-drug regimens based on two NRTIs and one protease inhibitor (PI; highly active antiretroviral therapy [HAART]) were analyzed by Peto's method. RESULTS: A significant virological response was observed in patients treated with NNRTIs (odds ratio [OR] 3.6; 95% CI, 2.2-6.0), particularly in naïve patients (OR 7.4; 95% CI, 4.1-13.5). A fair reduction of HIV disease progression was also observed in patients treated with NNRTIs (OR 0.8; 95% CI, 0.6-1.0). Moreover, a significantly lower rate of HIV progression was observed in patients with a CD4 + lymphocyte count below 100/mm(3). Five RCTs comparing two NRTIs and one NNRTI to HAART were subsequently evaluated. A slightly higher rate of virological response was observed with NNRTIs (OR 1.6; 95% CI, 1.1-2.1), whereas no difference was observed concerning progression of HIV disease. CONCLUSION: Antiretroviral therapy including NVP or EFV was more effective in reducing viral load than therapy with only two NRTIs and was slightly more effective than HAART. Effectiveness in delaying HIV disease progression was less evident, even though lower rate of progression was observed in patients with advanced HIV infection compared to two NRTIs alone.

Alkynes↗
PubMedDate not supplied

Avascular necrosis in HIV-infected patients receiving antiretroviral treatment: study of seven cases.

PURPOSE: We analyzed clinical, radiological, scintigraphical, epidemiological, and immunological data in a group of HIV-infected patients with osteonecrosis. METHOD: The first case was diagnosed in June 1997, and 6 more were identified thereafter among 1,650 attended patients (0.36%). Mean age was 37.6 years (33-46), and all were men. Mean CD4+ lymphocyte count was 501 cells/microL (98-1156), viral load was undetectable (<50 copies/mL) in 5 patients, and only 2 had AIDS diagnosis. Two patients were alcohol abusers, 1 received corticosteroids, and 3 had hypertrigliceridemia. One patient was treated with d4T plus 3TC, and the remaining received HAART. In 2 patients, lipodystrophy was simultaneously diagnosed. RESULTS: Mean time between first dose of antiretroviral drugs and onset of symptoms was 12 months (2-24). All patients developed pain and functional impotence of the affected joints, and the diagnosis was confirmed by imaging techniques. Distribution of the affected sites was as follows: both hips in 5 cases, femoral external condyle in 1, and multiple joints in 1. In 4 cases, the protease inhibitor was interrupted; there was clinical improvement in 2 of these cases. The unfavorable outcome of the remaining cases required surgical intervention. CONCLUSION: Metabolic and bone diseases should be considered a complication of HIV infection that is of growing importance.

Adult↗