T cell subsets and cytomegalovirus retinitis in human immunodeficiency virus-infected patients

A case-control study was done to investigate the relationship between T cell subsets and cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected subjects with or without CMV retinitis and CD4+ cell counts of <0.050 x 10(9)/L. Cell surface markers on peripheral blood lymphocytes were evaluated using flow cytometry. Patients with CMV retinitis had significantly lower levels of CD8+ cells (median: 0.152 x 10(9)/L) compared with levels for controls (median: 0.296 x 10(9)/L, P < .001). Significant down-regulation of costimulatory molecule CD28+ and lymphocyte function-associated antigen-1 (LFA-1) expression was observed in patients versus controls (CD28+: 0.048 x 10(9)/L vs. 0.143 x 10(9)/L, P < .001; LFA-1: 0.238 x 10(9)/L vs. 0.400 x 10(9)/L, P < .001), but no significant differences were noted for NK cells. We propose that progressive loss of the CD3+ CD8+ cell subset and down-regulation of CD28 and LFA-1 accessory molecules are associated with an increased risk of CMV retinitis in HIV-infected patients.     

Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus retinitis and elevated CD4+ counts

OBJECTIVE: To determine whether maintenance therapy can be discontinued safety in patients with quiescent cytomegalovirus retinitis (CMVR) and increased CD4+ counts after treatment with highly active antiretroviral therapy (HAART). DESIGN: A prospective observational case series. PARTICIPANTS: Eight human immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were taking HAART and had CD4+ counts above 100 cells/microliter elected to discontinue anti-CMV maintenance treatment. INTERVENTION: Biweekly-to-monthly indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts, and quarterly HIV viral loads were ordered. MAIN OUTCOME MEASURES: Twelve previously affected eyes were examined for evidence of recurrent retinitis, which was defined as any retinal whitening, border opacification, or expansion of areas of retinal pigment epithelial (RPE) atrophy greater than 750 microns. Four previously unaffected fellow eyes were observed for new CMVR. RESULTS: There was no reactivation or progression of retinitis in any patient during the mean follow-up interval of 11.4 months (range, 3-16 months). No previously unaffected eye developed CMVR. CD4+ remained elevated in all patients (range, 70-725; mean, 255). The HIV viral load ranged from undetectable to 139,000 copies. CONCLUSION: Discontinuation of maintenance therapy may be considered in patients with HAART-induced elevated CD4+ counts above 100 cells/microliter, prolonged relapse-free intervals during the reconstitution period before CD4+ counts rise above 100 cells/microliter, and completely quiescent retinitis characterized by RPE scarring only. Reduced risks of drug toxicity and drug-resistant organisms are potential benefits. Close observation for evidence of recurrent retinitis is indicated.     

Syphilitic uveitis in human immunodeficiency virus-infected patients

Congenital cystic adenomatoid malformation of the lung (CCAM) is characterized by an adenomatoid proliferation of bronchiole-like structures and cysts formation. The condition is most commonly found in newborns and children and it may be associated with other malformations; rarely, the presentation is delayed until adulthood. This paper presents a case of CCAM in a 62-year-old male, who presented with recurrent bacterial pneumonias and breathlessness one exertion. The chest X-rays and CT scan revealed a patchy opacity in the right lower pulmonary zone. Bronchoscopic examination was normal. At surgery, a mass involving the right lower and middle lobes, and enlargement of hilar lymph nodes were found. A bilobectomy was performed without complications. Examination of the gross specimen showed a lesion characterised by multiple small cysts, all less than 1 cm in diameter; they were lined predominately by columnar epithelium, occasionally by ciliated epithelium. Rare cysts were lined by foreign body giant cells. Elastic fibers and smooth muscle were present within the cysts wall. Peripherally, there were normal alveoli and bronchioli mixed with cysts, and plasmalymphocytic infiltrates. The final diagnosis was Stocker's Type II CCAM of the lung. CCAM of the lung is a rare development lesion of the lung and it has no sexual predilection. It is usually unilateral and sublobar or lobar in size, but occasionally it can be multilobar. Typical histologic feature of CCAM are adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands. Inflammatory changes are not found in infants, but may be present in adult patients. Based on the size of the cysts, CCAM may be classified into three different types: type I characterised by multiple cysts, over than 1 cm in diameter; type II with smaller cysts, less than 1 cm in diameter; type III that shows solid lesions composed of bronchiole-like structures. Type II is commonly found in childhood, but is occasionally seen in adult patients, as that one in our report. The insult probably occurs between 4th and 7th week of fetal life. The etiologic agent is unknown. The histologic diagnosis of CCAM is difficult in adult patient, perhaps because of supervening infections that sometimes distort the underlying diagnostic pathologic appearances and make them difficult to recognise, as happened in our case. From the clinical point of view, most of the lesions cause severe respiratory failure; in adult individuals the diagnosis is difficult, since there are very few relevant symptoms and signs. The patients can present with fever, recurrent infections, breathlessness and haemoptysis. The chest X-rays abnormalities are not specific and include homogeneous or multicystic opacities. Similarly, other diagnostic methods add no further useful informations. Surgical treatment is necessary also in adult patients, because of the risk of recurrent pulmonary infections and malignancies associated with CCAM. Lobectomy is the treatment of choice, but sometimes a larger resection is required, when the lesion involves more than one lobe.     

Acyclovir-resistant herpes zoster in human immunodeficiency virus-infected patients: results of foscarnet therapy

We retrospectively studied 18 consecutive cases of acyclovir-resistant zoster. All the patients had chronic skin lesions that failed to heal despite treatment with intravenous acyclovir (30 mg/[kg.d]) in 15 cases and oral acyclovir (4 g/d) in three cases for > 10 days. The mean CD4+ cell count was 20 x 10(6)/L. The mean number of previous zoster episodes was 1.53. Fifteen of the 16 patients evaluable for previous acyclovir treatment had received the drug. Thirteen patients were treated with intravenous foscarnet (200 mg/[kg.d]) for a mean of 17.8 days. Complete healing was observed in 10 (77%) of the 13 treated patients. Zoster relapsed after cessation of foscarnet therapy in five of the 10 responding patients. The median time to relapse was 110 days. Four patients died of varicella-zoster virus-associated visceral complications. These results show that acyclovir-resistant zoster has a poor prognosis but responds well to foscarnet therapy.     

Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients

Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacokinetic model. Parameter estimates were the absorption rate constant (0. 201/h), clearance/bioavailability (CL/F; 60.9 liters/h), volume of the central compartment/bioavailability (231 liters), intercompartmental clearance (60.3 liters/h), and volume of the peripheral compartment/bioavailability (Vp/F; 1,050 liters). The distribution and elimination half-lives were 1.24 and 25.4 h, respectively. The covariates tested for influence on CL/F and Vp/F were sex, age, weight, height, body surface area, tobacco smoking, drug addiction, alanine aminotransferase levels, creatinine clearance, total protein, bilirubin, numbers of CD4(+) cells, presence of diarrhea, cachexia index, rifabutin use (prophylaxis versus therapy), rifabutin dose, study site, and the concomitant administration of clarithromycin, fluconazole, phenobarbital, ciprofloxacin, azithromycin, or benzodiazepines. The only statistically significant effects on rifabutin pharmacokinetic parameters were a 27% decrease in Vp/F due to the concomitant administration of azithromycin and a 39% increase in Vp/F due to tobacco smoking. Such effects may be considered clinically unimportant. Our results confirm the lack of a correlation of rifabutin pharmacokinetic parameters with parameters of disease progression and gastrointestinal function. Also, the lack of a correlation with covariates which were previously found to be significant, such as concomitant fluconazole and clarithromycin use, may suggest that the effect of such covariates may be less important in the real clinical setting, in which several concomitant factors may influence pharmacokinetic parameters, with an overall effect of no apparent correlation.     

Oral manifestations of human immunodeficiency virus-infected patients in Taiwan

To understand the characteristic clinical features of human immunodeficiency virus (HIV)-related oral lesions and determine the prevalence of various oral lesions in HIV-infected patients in Taiwan, we conducted a cross-sectional study of 207 HIV-infected patients at the Taipei Municipal Institute for Venereal Disease Control. Overall, 108 (52.2%) patients had at least one oral lesion. The most common oral manifestation of HIV infection among these 207 patients was oral hairy leukoplakia (OHL, 29.5%), followed by candidiasis (12.1%), xerostomia (10.6%), aphthous ulcers (8.7%), and linear gingival erythema (5.8%). Less frequently encountered oral lesions included leukoplakia (1.9%), papilloma (1.4%), necrotizing ulcerative periodontitis (1.0%), Kaposi's sarcoma (1.0%), herpes simplex (0.5%), Burkitt's lymphoma (0.5%), and parotid gland enlargement (0.5%). Thirty-one (15%) patients had multiple oral lesions. Patients with oral candidiasis or multiple oral lesions had significantly lower mean CD4 lymphocyte counts and CD4/CD8 lymphocyte ratios than those without any oral lesions (p < 0.05). Chi-square analysis revealed that patients with CD4 lymphocyte counts below 200 cells/mm3 were more prone to have OHL (p < 0.002), oral candidiasis (p < 0.001) and multiple oral lesions (p < 0.001). Those with CD4/CD8 lymphocyte ratios below 0.4 were more likely to have OHL (p < 0.02), oral candidiasis (p < 0.01) and multiple oral lesions (p < 0.02) than those with higher counts. In conclusion, the occurrence of oral lesions, especially OHL and oral candidiasis, is fairly common in Taiwanese HIV-infected patients.     

Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients

Thrombocytopenia has been characterized in six patients infected with human immunodeficiency virus (HIV) with respect to the delivery of viable platelets into the peripheral circulation (peripheral platelet mass turnover), marrow megakaryocyte mass (product of megakaryocyte number and volume), megakaryocyte progenitor cells, circulating levels of endogenous thrombopoietin (TPO) and platelet TPO receptor number, and serum antiplatelet glycoprotein (GP) IIIa49-66 antibody (GPIIIa49-66Ab), an antibody associated with thrombocytopenia in HIV-infected patients. Peripheral platelet counts in these patients averaged 46 +/- 43 x 10(3)/microL (P = . 0001 compared to normal controls of 250 +/- 40x 10(3)/microL), and the mean platelet volume (MPV) was 10.5 +/- 2.0 fL (P > 0.3 compared with normal control of 9.5 +/- 1.7 fL). The mean life span of autologous 111In-platelets was 87 +/- 39 hours (P = .0001 compared with 232 +/- 38 hours in 20 normal controls), and immediate mean recovery of 111In-platelets injected into the systemic circulation was 33% +/- 16% (P = .0001 compared with 65% +/- 5% in 20 normal controls). The resultant mean peripheral platelet mass turnover was 3.8 +/- 1.5 x 10(5) fL/microL/d versus 3.8 +/- 0.4 x 10(5) fL/microL/d in 20 normal controls (P > .5). The mean endogenous TPO level was 596 +/- 471 pg/mL (P = .0001 compared with 95 +/- 6 pg/mL in 98 normal control subjects), and mean platelet TPO receptor number was 461 +/- 259 receptors/platelet (P = .05 compared with 207 +/- 99 receptors/platelet in nine normal controls). Antiplatelet GPIIIa49-66Ab levels in sera were uniformly increased in HIV thrombocytopenic patients (P < .001). In this cohort of thrombocytopenic HIV patients, marrow megakaryocyte number was increased to 30 +/- 15 x 10(6)/kg (P = .02 compared with 11 +/- 2.1 x 10(6)/kg in 20 normal controls), and marrow megakaryocyte volume was 32 +/- 0.9 x 10(3) fL (P = .05 compared with 28 +/- 4.5 x 10(3) fL in normal controls). Marrow megakaryocyte mass was expanded to 93 +/- 47 x 10(10) fL/kg (P = .007 compared with normal control of 31 +/- 5.3 x 10(10) fL/kg). Marrow megakaryocyte progenitor cells averaged 3.3 (range, 0.4 to 7.3) CFU-Meg/1,000 CD34(+) cells compared with 27 (range, 0.1 to 84) CFU-Meg/1,000 CD34(+) cells in seven normal subjects (P = .02). Thus, thrombocytopenia in these HIV patients was caused by a combination of shortening of platelet life span by two thirds and doubling of splenic platelet sequestration, coupled with ineffective delivery of viable platelets to the peripheral blood, despite a threefold TPO-driven expansion in marrow megakaryocyte mass. We postulate that this disparity between circulating platelet product and marrow platelet substrate results from direct impairment in platelet formation by HIV-infected marrow megakaryocytes.     

Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects

The AMPLICOR cytomegalovirus (CMV) test, a new qualitative assay for the detection of CMV DNA in plasma, was compared to conventional methods and quantitative PCR (Q-PCR) assays by using leukocytes and plasma from 179 blood samples from subjects with AIDS. For the diagnosis of CMV disease, cell-based assays such as a Q-PCR with polymorphonuclear leukocytes (Q-PCR-PMNL) and a pp65 antigenemia assay had the highest sensitivities but suffered from a lack of specificity. The best agreement between the results of the Q-PCR-PMNL assay and those of the AMPLICOR test was found when a threshold diagnostic value of 690 copies per 10(5) cells was selected for the Q-PCR-PMNL assay. In that context, the AMPLICOR CMV test had a sensitivity of 96.4% and a specificity of 95.3% when results were compared to results of the cell-based PCR assay. This threshold was close to the one described as associated with the best sensitivity and specificity for the diagnosis of CMV disease in a recently published study (4). Blood samples that tested positive by the Q-PCR-PMNL assay but negative by the AMPLICOR CMV test were associated with viral loads (mean, 785 copies, median, 96 copies per 10(5) leukocytes) lower than the viral loads of blood samples that tested positive by both assays (mean, 21,452 copies; median, 9,784 copies per 10(5) leukocytes) (P = 0.003). The AMPLICOR CMV test gave positive results at least 48 days before the development of symptomatic CMV disease in a longitudinal analysis of a limited subset of patients (n = 6) from whom sequential specimens were available for testing. In conclusion, the AMPLICOR CMV test is a very convenient assay combining rapidity, simplicity, and the possibility of batch testing. A positive result by this test seems particularly important since this implies, in most instances, the presence or the imminence of CMV disease, although a negative test result does not rule out disease.     

Duodenal intraepithelial and lamina propria T lymphocytes in human immunodeficiency virus-infected patients with and without diarrhoea

BACKGROUND: Diarrhoea is an important problem in human immunodeficiency virus (HIV)-infected patients. Intestinal pathologic conditions may arise from changes in local immunocyte populations. The aims of our study were to establish the histologic features of the duodenal mucosa of HIV-infected patients and to determine a) the phenotype of small-intestinal-intraepithelial (IELs) and lamina propria (LPLs)-lymphocytes; b) their degree of activation and differentiation within the lamina propria; and c) their relation to the presence of diarrhoea. METHODS: Distal duodenal biopsy specimens were obtained prospectively from 29 HIV-infected patients-11 patients with diarrhoea (group 1) and 18 patients without diarrhoea (group 2)- and from 42 patients who had neither any risk factor for HIV nor diarrhoea (group 3). Histopathologic and immunohistochemical studies were combined with flow cytometric analysis, after separation of the mucosal intraepithelial compartment from the lamina propria. RESULTS: The median number of IELs and the percentage of gamma delta IELs were both unchanged in HIV-infected patients as compared with controls. In HIV-infected patients LP CD4 cells were decreased, and LP CD8 cells increased. No significant difference was found in the expression of CD25 or CD27 within the LP CD8 populations of HIV-infected patients in groups 1 and 2. CONCLUSIONS: These findings suggest that the occurrence of diarrhoea in HIV-infected patients is unrelated to IEL and LPL phenotype.     

Detection of cytomegalovirus in plasma and cerebrospinal fluid specimens from human immunodeficiency virus-infected patients by the AMPLICOR CMV test

We have developed the AMPLICOR CMV Test, which is rapid and sensitive for the detection of cytomegalovirus (CMV) in plasma and cerebrospinal fluid (CSF) specimens. The test incorporated an internal control in the reaction mixture to monitor the amplification efficiency and the presence of inhibitors. The AMPLICOR CMV Test was very specific in detecting 12 clinical CMV isolates and four laboratory CMV strains tested. Cross-reactivity with 26 non-CMV pathogens was not observed. The AMPLICOR CMV Test requires only 50 microl of specimen (plasma or CSF) for processing. The performance of the AMPLICOR CMV Test was compared to those of the CMV antigenemia assay and the conventional tube culture method. Among 112 plasma specimens from 43 human immunodeficiency virus-infected patients, CMV was detected in 20 (18%) of the specimens by the AMPLICOR CMV Test, 21 (19%) of the specimens by the CMV antigenemia assay, and 10 (9%) of the specimens by culture. In CSF specimens from AIDS patients, CMV was detected in 10 of 58 (17%) specimens tested by the AMPLICOR CMV Test, 5 of 28 (18%) specimens tested by the antigen assay, and none of the 25 specimens tested by culture. While the performance of the AMPLICOR CMV Test in this study was comparable to that of the CMV antigen assay, processing of specimens by the AMPLICOR CMV Test was much simpler than that by the antigen assay; in addition, the antigen assay requires greater than 10(5) leukocytes from blood or 1 ml of CSF to perform the assay. Our study suggested that the AMPLICOR CMV Test could provide a rapid and sensitive assay for the detection of CMV in plasma and CSF specimens.     

Cancers in human immunodeficiency virus-infected children

Although the exact incidence of cancers in human immunodeficiency virus (HIV)-infected children is not clear, an excess of non-Hodgkin's lymphomas and soft tissue tumors as well as a multitude of otherwise rare tumors in childhood, such as cervical, thyroid, or pulmonary carcinoma, has been reported. In contrast to the findings in HIV-infected adults, Kaposi's sarcoma is rare in children in industrialized countries but not in children living in the sub-Saharan area. Treatment of the neoplastic disease is often complicated by multiple HIV-associated organ dysfunctions as well as drug interactions and infectious complications secondary to severe immunosuppression. Nonetheless, preliminary results with dose-intensive, but brief, chemotherapeutic regimens have been encouraging, and HIV-infected children who develop cancer are likely to benefit from aggressive treatment combined with adequate supportive care. Furthermore, insights gained from the study and treatment of this very challenging group of patients may benefit other immunocompromised hosts as well as increase our understanding of oncogenesis in general.     

Multidose pharmacokinetics of ritonavir and zidovudine in human immunodeficiency virus-infected patients

The effect of coadministration of ritonavir and zidovudine (ZDV) on the pharmacokinetics of these drugs was investigated in a three-period, multidose, crossover study. Eighteen asymptomatic, human immunodeficiency virus-positive men were assigned randomly to six different sequences of the following three regimens: ZDV (200 mg every 8 h [q8h] alone for 4 days, ritonavir (300 mg q6h) alone for 4 days, and ZDV with ritonavir for 4 days. Ritonavir pharmacokinetics were unaffected by coadministration with ZDV. However, ZDV exposure was reduced by about 26% (P < 0.05) in the presence of ritonavir. The maximum concentration in (Cmax) of ZDV plasma decreased from 748 +/- 375 (mean +/- standard deviation) to 546 +/- 296, and area under the concentration-time curve from 0 to 24 h (AUC0-24) decreased from 3,052 +/- 1,007 to 2,261 +/- 715 when coadministered with ritonavir. In contrast, the ZDV elimination rate constant was unaffected by ritonavir, suggesting that there was no change in ZDV systemic metabolism. Correspondingly, differences in ZDV-glucuronide Cmax and AUC were not statistically significantly different between regimens (P > 0.31). Also, there were no apparent differences in the formation of 3'-amino-3'-deoxythymidine or in the adverse event profiles between the regimens. The lack of change in ritonavir pharmacokinetics suggests that dosage adjustment of ritonavir is unnecessary when it is administered concurrently with ZDV. The clinical relevance of a 26% reduction in ZDV exposure when ZDV is administered with ritonavir is unknown. In addition to other multidrug regimens, the long-term safety and efficacy of coadministration of ritonavir and ZDV is being investigated.     

Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.     

Development of quinolone-resistant Campylobacter fetus bacteremia in human immunodeficiency virus-infected patients

Campylobacter fetus subspecies fetus has been recognized as a cause of systemic illness in immunocompromised hosts, including relapsing bacteremia in human immunodeficiency virus (HIV)-infected patients. Acquired resistance to quinolone therapy, while reported for a variety of bacteria, including Campylobacter jejuni, has not been previously documented for C. fetus. Two cases of quinolone-resistant C. fetus bacteremia were detected in HIV-infected patients. Cloning and nucleotide sequencing of the C. fetus gyrA gene in the 2 resistant isolates demonstrated a G-to-T change that led to an Asp-to-Tyr amino acid substitution at a critical residue frequently associated with quinolone resistance. In addition, comparison of the pre- and posttreatment isolates from 1 patient documented outer membrane protein changes temporally linked with the development of resistance. Relapsing C. fetus infections in quinolone-treated HIV-infected patients may be associated with the acquisition of resistance to these agents, and this resistance may be multifactorial.     

Long-term predictive value of a single cytomegalovirus (CMV) DNA PCR assay for CMV disease in human immunodeficiency virus-infected patients

Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegalovirus (CMV) disease in human immunodeficiency virus infection. For a preemptive strategy to be considered, patients at highest risk for CMV disease need to be easily and accurately identified. In this study, the sensitivity, specificity, positive predictive value, and negative predictive value of a single CMV DNA PCR assay for the subsequent development of CMV disease were 0.75, 0.89, 0.75, and 0.89, respectively.     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

Pharmacokinetic interaction of megestrol acetate with zidovudine in human immunodeficiency virus-infected patients

This nonrandomized, two-period crossover study was performed to assess whether concomitant administration of megestrol acetate influences the steady-state pharmacokinetics of zidovudine and its inactive 5'-O-glucuronide metabolite. Twelve HIV-positive, asymptomatic male volunteers received a 100-mg oral capsule dose of zidovudine at least 30 min before meals five times a day at 0700, 1100, 1500, 1900, and 2300 h on study days 1 to 3 and a single 100-mg dose at 0700 h on day 4. On days 5 to 17, 800 mg of megestrol acetate, as a 40-mg/ml aqueous suspension, was administered orally immediately before the 0700 h dose of zidovudine. On days 5 to 16, zidovudine was also administered at 1100, 1500, 1900, and 2300 h. Serial blood samples were collected for 12 h after the single 100-mg dose of zidovudine on days 4 and 17; trough samples were also obtained just before the 0700 h dose on days 2 to 4 and 15 to 17. Levels of zidovudine and its glucuronide in plasma were assayed by a validated radioimmunoassay. Statistical analysis of trough plasma level data indicated that steady-state levels of zidovudine and its glucuronide in plasma had been attained when pharmacokinetic assessments were made on days 4 and 17. When megestrol acetate and zidovudine were coadministered for 13 days, differences of -14, -6.5, and -4.6% in mean zidovudine peak concentration and areas under the curve at 0 to 4 and 0 to 12 h, respectively, +22.5% in mean trough concentration, +2.6% in mean plasma half-life, and no change in median time to peak were observed compared to conditions when zidovudine was administered alone; for zidovudine 5'-O-glucuronide the respective differences were -9, -7.3, -4.4, +2.3, and +10% and no change. None of the differences were statistically significant (P > 0.05). Concomitant therapy with megestrol acetate, at the dose employed to treat anorexia, cachexia, or an unexplained, significant weight loss in AIDS patients, did not alter the steady-state pharmacokinetics of zidovudine or its 5'-O-glucuronide metabolite.