Biomedical subjects

R C Reichman

Publications and source records attributed to R C Reichman.

At least 19 recordsLinked to original sources

PubMed1997

HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine.

Previous studies have shown that the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase mutation Y181C, which confers high-level resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), develops rarely during therapy with NNRTIs plus zidovudine. To determine whether didanosine (ddI) is also effective in preventing the emergence of Y181C, we analyzed delavirdine (DLV) susceptibilties and reverse transcriptase sequences of isolates obtained from patients enrolled in a pharmacokinetic study of DLV and ddI. Nine NNRTI-naive patients were evaluated. Seven received DLV/ddI and two received DLV/ddI/zidovudine. Median durations of prior zidovudine and ddI were 26 and 15 months, respectively. Isolates from eight of nine patients had a mutation(s) associated with nucleoside resistance at entry. After treatment with DLV and ddI alone, isolates from five of seven patients developed Y181C, four in combination with K103N. Thus, in this group of nucleoside-experienced patients, combination therapy with DLV/ddI did not prevent the emergence of Y181C.

Adult↗

PubMed1997

A randomized, double-blind trial of parenteral low dose versus high dose interferon-beta in combination with cryotherapy for treatment of condyloma acuminatum.

Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts. Subjects were randomized to receive subcutaneous injections of either 2 x 10(6) or 4 x 10(6) IU/m2 of IFN-beta (Biogen) three times a week for a total of 6 weeks. Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals. Systemic side- effects were modest in intensity and included fever, chills, myalgia, and headaches (flu-like symptoms). During the first 2 weeks of therapy, they were more common in the high dose group than in the low dose group (P = 0.02). Using survival analysis, there was no significant difference between the two groups in rates of resolution of warts present at baseline (P = 0.62). However, the rate of new lesion formation during the study was significantly lower in the high dose group (P = 0.04).

Adult↗

PubMed1997

Results of a screening program for Chlamydia trachomatis infection in men attending a sexually transmitted diseases clinic.

BACKGROUND: Screening programs for Chlamydia trachomatis infection in men are uncommon. GOAL: To report the results of a screening program using the Syva MicroTrak direct fluorescent antibody (DFA) test (Palo Alto, CA) for diagnosis of C. trachomatis infection in men attending a sexually transmitted diseases (STD) clinic. STUDY DESIGN: DFA testing was performed on an additional urethral specimen obtained during male new patient or new complaint visits between July 1, 1994 and June 30, 1996. Positive and negative test results were compared according to patient demographic characteristics, symptoms, diagnoses, and treatments received. RESULTS: 474 of 9,662 (4.9%) DFA tests were positive. Men with chlamydial infection were more likely to be African-American (p < 10(-7)) and less than 24 years of age (p < 10(-7)). C. trachomatis infection was present in 10.7% of those with gonorrhea and 10.0% of those with nongonococcal urethritis. Forty percent of chlamydia cases were asymptomatic, and 97% were treated at the visit owing to existing clinic protocols. CONCLUSIONS: C. trachomatis infection is common and often asymptomatic in men attending STD Clinics. Infected men are likely to be young and African-American. Routine screening with the Syva MicroTrak DFA test will detect unsuspected cases of chlamydial infection; however, in the clinic in this report, most cases were already treated according to standard clinic protocols.

Adolescent↗

PubMed1996

Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group.

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, combined treatment with several agents may increase the effectiveness of antiviral therapy. We studied the safety and efficacy of saquinavir, an HIV-protease inhibitor, given with one or two nucleoside antiretroviral agents, as compared with the safety and efficacy of a combination of two nucleosides alone. METHODS: In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine. The 302 patients enrolled had CD4+ counts of 50 to 300 cells per cubic millimeter and had previously received zidovudine for a median of 27 months. The study lasted 24 weeks, with an optional double-blind extension period of an additional 12 to 32 weeks. RESULTS: Ninety-six percent of the patients completed the 24-week study. In all three treatment groups, CD4+ cell counts rose at first and then fell gradually. The normalized area under the curve for the CD4+ count was greater with the three-drug combination than with either saquinavir and zidovudine (P=0.017) or zalcitabine and zidovudine (P<0.001). There were significantly greater reductions in plasma HIV with the three-drug combination than with the other regimens when peripheral-blood mononuclear cells were cultured for HIV and HIV RNA was assessed, and there were greater decreases in serum neopterin and beta2-microglobulin levels. There were no major differences in toxic effects among the three treatments. CONCLUSIONS: Treatment with saquinavir, zalcitabine, and zidovudine was well tolerated. This drug combination reduced HIV-1 replication, increased CD4+ cell counts, and decreased levels of activation markers in serum more than did treatment with zidovudine and either saquinavir or zalcitabine. Studies are warranted to evaluate whether the three-drug combination will reduce morbidity and mortality.

Adult↗

PubMed1996

Serologic response to treatment of syphilis in patients with HIV infection.

BACKGROUND: Much controversy exists concerning the manifestations, therapy, and response to treatment of syphilis in patients coinfected with the human immunodeficiency virus (HIV). OBJECTIVE: To assess the effect of HIV infection on the serologic response to treatment of patients with syphilis. METHODS: Sixty-four HIV-seropositive patients with syphilis were matched with 64 patients with syphilis who were HIV negative. Matching criteria included age (+/- 5 years), sex, race, initial rapid plasma reagin (RPR) titer (+/- 1 dilution), and stage of syphilis at entry. There were 26 matched patients with early syphilis, 26 matched patients with late syphilis, and 12 matched patients with biological false-positive RPR. The HIV-positive patients with early syphilis received three doses of penicillin G benzathine. All other patients received treatment as recommended by the Centers for Disease Control and Prevention, Atlanta, Ga. Our study's major end points were clinical and serologic response to treatment. RESULTS: All 16 patients with symptomatic syphilis were cured. No patient developed clinical signs of neurosyphilis during the 12-month follow-up period. Twenty-nine (56%) of 52 HIV-positive patients with early or late syphilis did not have a fourfold decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52 matched controls (P = .06). No unique characteristics identifying patients who did not respond serologically could be established. The HIV-positive patients with initial RPR less than 1:32 experienced a significantly slower decrease in RPR at 12 months than did the controls (P < .001). CONCLUSIONS: Patients with syphilis who are HIV positive are less likely to experience serologic improvement after recommended therapy than are patients with syphilis who are HIV negative. Patients with HIV infection who contract syphilis should receive intensive and prolonged follow-up, and consideration should be given to designing alternative regimens.

Adult↗

PubMed1995

Effects of zidovudine use during pregnancy on resistance and vertical transmission of human immunodeficiency virus type 1.

The resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and the vertical transmission of the virus were assessed among all 62 HIV-1-infected pregnant women identified prior to delivery at one institution. HIV-1 was transmitted to infants from 11 (26%) of 42 women who did not receive oral zidovudine but from only 1 of 20 women given such treatment (P = .04). Isolates of HIV-1 from 16 of the 20 zidovudine-treated women were available. Twelve of 16 isolates were wild-type for pol codons 41, 67, 70, 215, and 219; two (one susceptible and one moderately resistant to zidovudine) had mutations at codon 70; and two (both highly resistant to zidovudine) had mutations at codons 41 and 215. The virus was vertically transmitted from a woman infected with one of the highly resistant strains, and the infant's isolate was highly resistant to zidovudine. These limited data suggest that maternal treatment with oral zidovudine reduces the rate of vertical transmission of HIV-1 but that vertical transmission of virus resistant to zidovudine can occur.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Phase I study of atevirdine, a nonnucleoside reverse transcriptase inhibitor, in combination with zidovudine for human immunodeficiency virus type 1 infection. ACTG 199 Study Team.

Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.

Adult↗

PubMed1995

Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy.

Human immunodeficiency virus type 1 (HIV-1) isolates from 2 patients who received didanosine (ddI) monotherapy for > 2 years were analyzed for reverse transcriptase (RT) mutations by sequencing of proviral DNA from peripheral blood mononuclear cell cultures. One patient was otherwise antiretroviral-naive; the other had received zidovudine for 5 months before beginning ddI therapy. Isolates obtained from both patients before initiation of ddI monotherapy were free of HIV-1 RT mutations associated with zidovudine or ddI resistance. However, after prolonged ddI monotherapy, mutations associated with zidovudine resistance (M41L, D67N, K70R, and/or T215Y) were detected in HIV-1 isolates from both patients. There was no evidence that surreptitious use of zidovudine or technical artifact caused these findings. This observation suggests that prolonged ddI monotherapy may decrease the efficacy of subsequent zidovudine therapy in some patients.

Acquired Immunodeficiency Syndrome↗

PubMed1995

The predictive value of changes in serologic and cell markers of HIV activity for subsequent clinical outcome in patients with asymptomatic HIV disease treated with zidovudine.

OBJECTIVE: To determine if serologic marker responses to zidovudine treatment during the first year of antiretroviral therapy could predict subsequent HIV disease progression independently of absolute CD4 lymphocyte responses. METHODS: We conducted a case-control study in patients with asymptomatic HIV disease, who were initiating zidovudine therapy in a randomized, prospective trial. A total of 102 patients who progressed to AIDS or advanced AIDS-related complex and 177 randomly selected controls matched by baseline CD4 cell count and duration of follow-up had serum samples (from prior to and at 8, 16, 32 and 48 weeks of zidovudine treatment) assayed for acid-disassociated HIV p24 antigen, beta 2-microglobulin (beta 2M), neopterin, soluble interleukin (IL)-2 receptor, soluble CD4 protein and soluble CD8 protein. RESULTS: Median time to event for cases was 20.2 months; median follow-up on study was 35.4 months for controls. After controlling for absolute CD4 count at baseline, increased baseline serum concentrations of HIV p24 antigen, beta 2M, neopterin, and soluble IL-2 receptor were highly predictive of increased risk of HIV disease progression. In a multiple logistic regression model, controlling for baseline marker values, change in beta 2M consistently added independent value to change in CD4 count in predicting subsequent risk of disease progression. CONCLUSIONS: Monitoring serum immunologic markers, in particular beta 2M, in addition to absolute CD4 lymphocyte counts prior to and within the first 4 months after initiating dideoxynucleoside therapy can increase the accuracy of estimations of subsequent long-term risk of clinical HIV disease progression. This information may be useful to clinicians and patients who are making decisions about initiating or changing antiretroviral therapy.

AIDS-Related Complex↗

PubMed1994

The duration of zidovudine benefit in persons with asymptomatic HIV infection. Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group.

OBJECTIVE: To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4+ cell count. DESIGN AND INTERVENTIONS: Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo. SETTING: University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019. PATIENTS: A total of 1565 asymptomatic HIV-infected subjects with entry CD4+ cell counts less than 0.50 x 10(9)/L (500/microL). MAIN OUTCOME MEASURE: Time to progression to AIDS or death. RESULTS: During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P = .008, .004, .007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P = .002, .08, .04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4+ cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo. CONCLUSIONS: Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry CD4+ cell counts less than 0.30 x 10(9)/L (300/microL). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts.

PURPOSE: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. PATIENTS AND METHODS: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. RESULTS: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. CONCLUSION: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease.

Adult↗

PubMed1994

Human papillomavirus (HPV) type 11 recombinant virus-like particles induce the formation of neutralizing antibodies and detect HPV-specific antibodies in human sera.

Recombinant human papillomavirus type 11 (HPV-11) virus-like particles (VLPs) were tested for their ability to induce the formation of neutralizing antibodies, and were also tested for serodiagnostic capabilities in an ELISA in comparison with HPV-11 whole virions. VLPs, purified by CsCl density gradient centrifugation from the cell-free supernatant of Ac11L1-infected Sf9 suspension cell cultures, were used to immunize rabbits and anti-VLP antibodies were tested in the athymic mouse model of HPV-11 infection. Pretreatment of infectious HPV-11 virions with the immune serum of VLP-treated animals caused a marked reduction of graft growth (P < 10(-4)) and viral gene expression (P < 10(-4)), similar to the effects obtained using whole virion postimmune serum, and consistent with immune neutralization. To assess the serodiagnostic capabilities of VLPs, a VLP ELISA was developed and used to analyse sera that were tested previously in an HPV-11 whole virion ELISA. Specific antibodies were detected in 49% of patients' sera (P = 2 x 10(-4)), and individual VLP seroreactivities correlated with those previously obtained using whole virions as the antigen (r = 0.87; P < 10(-6)). These results indicate that recombinant VLPs can be used to elicit a neutralizing antibody response, and can substitute faithfully for native virions in the development of HPV-serodiagnostic immunoassays.

Animals↗

PubMed1994

Serological differentiation of human papillomavirus types 11, 16 and 18 using recombinant virus-like particles.

The L1 major capsid protein-coding sequences of human papillomavirus (HPV) types 11, 16 and 18 were expressed in the baculovirus system. Virus-like particles (VLPs) were purified from recombinant-infected Spodoptera frugiperda Sf9 cells and cell-free culture supernatants. Rabbits immunized with purified VLPs developed antibodies that reacted only with the specific VLP type used as the immunogen. In addition, rabbit antibodies raised against infectious HPV-11 virions only reacted with HPV-11 L1 VLPs and not with VLPs derived from either HPV-16 or HPV-18. These results suggest that HPV-11, HPV-16 and HPV-18 virions are antigenically distinct from one another. This observation should be considered in future studies of immune responses to HPV.

Animals↗

PubMed1994

Evaluation of temperature sensitivity of human papillomavirus type 11 by using the human xenograft severe combined immunodeficiency mouse model.

The temperature sensitivity of human papillomavirus type 11 was evaluated by using a human xenograft severe combined immunodeficiency mouse model. Incubation of the virus for 1 h at a temperature higher than 56 degrees C but lower than 72 degrees C was sufficient to inhibit the virally induced growth of infected human tissue. However, 100 degrees C was necessary to completely inactivate HPV type 11 genome expression.

Animals↗

PubMed1993

Evolution of the antibody response to human papillomavirus type 11 (HPV-11) in patients with condyloma acuminatum according to treatment response.

To evaluate the variation over time of seroreactivity to human papillomavirus type 11 (HPV-11) according to disease outcome, we selected a sample of 42 condyloma acuminatum patients from a group of subjects enrolled in a placebo-controlled trial of three alpha-interferon preparations administered parenterally for the treatment of condyloma acuminatum. This sample included 14 subjects who were cured by the end of follow-up (cured group) and 28 subjects who were not (failed group). For each individual, the first and last sera collected in the study were tested with an intact HPV-11 virion-based enzyme linked immunosorbent assay (ELISA). The sera of 20 nuns with no lifetime sexual exposure served as controls. The median optical density (OD) value of the first serum samples (as well as that of the last samples) from the patients, 0.155, was higher than that of the control sera, 0.073 (P = 2 x 10(-4)). Sensitivity of the assay was 50%. To test if evolution of seroreactivity in the seropositive patients was related to disease outcome after treatment, we examined the average percentage of daily change in OD between the two serum collections. The median OD in the cured group (n = 7) dropped by 0.05% a day whereas in the failed group (n = 11) it increased by 0.07% a day, a highly statistically significant difference (P = 0.006). It is concluded that changes in the seroreactivity to HPV-11 virions are related to outcome of condyloma acumination after treatment. Therefore, improved serological assays may eventually contribute to the monitoring of HPV disease activity.

Adult↗

PubMed1993

Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model.

We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11-infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum.

Animals↗

PubMed1993

Didanosine (ddI) and zidovudine (ZDV) susceptibilities of human immunodeficiency virus (HIV) isolates from long-term recipients of ddI.

Thirty HIV isolates, obtained from 15 patients before and after receiving single drug therapy with didanosine (ddI), were examined for sensitivity to ddI and zidovudine (ZDV) using a peripheral blood mononuclear leukocyte (PBML)-based assay. Fourteen of the patients had ARC, one had AIDS and 12 had received previous therapy with ZDV. After a median of 1 year of ddI therapy, isolates were significantly less sensitive to ddI than were isolates obtained prior to therapy (P = 0.03). A decrease in ddI sensitivity was observed in ten of the 15 isolate pairs. In contrast to ddI susceptibilities, sensitivity to ZDV increased over the same period of time (P = 0.03). Additional isolates were obtained from four patients who received ddI monotherapy for 2 years. Three of these isolates demonstrated no change in ddI sensitivity compared to baseline. No correlation could be made in this study between development of decreased ddI sensitivity and serum p24 levels, CD4 counts, or clinical outcome. Decreased ddI sensitivity occurs frequently among HIV isolates obtained from long-term recipients of ddI. This decreased sensitivity is modest in degree and is of unknown clinical significance.

AIDS-Related Complex↗

PubMed1993

Didanosine: long-term follow-up of patients in a phase 1 study.

Long-term follow-up of 44 patients with AIDS or AIDS-related complex (ARC) in a phase 1 trial of didanosine is reported. These patients were monitored for as long as 72 weeks (mean, 34 weeks) for toxicity and activity of didanosine. Pancreatitis and neuropathy, the major clinical toxicities, developed infrequently at the doses of didanosine (250-750 mg/d) employed during the latter part of the study. Consistent hematologic toxicity was not encountered; moreover, mean values for hematologic parameters such as hemoglobin concentration, white blood cell count, neutrophil count, lymphocyte count, and platelet count improved for up to 20-60 weeks. CD4 counts increased significantly through 10 weeks of therapy and in some patients remained at or above counts at enrollment for as long as 60 weeks. Serum concentrations of p24 antigen decreased significantly and remained at the decreased level for up to 48 weeks. An initial diagnosis of ARC (as opposed to AIDS), an initial CD4 count of > 100/mm3, and an increase in CD4 counts during the first 10 weeks of therapy were associated with a higher rate of survival and with lower rates of development of opportunistic infections and of other clinical manifestations of disease progression.

AIDS-Related Complex↗