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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 289 records · Page 16Linked to original sources

Double-blind, placebo-controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection.

To determine the efficacy of a herpes simplex virus type 2 (HSV-2) glycoprotein subunit vaccine, vaccine (50 micrograms) or placebo was administered intramuscularly at weeks 0, 4, and 22 to 161 persons who lacked HSV-2 antibodies and were sex partners of persons with recurrent genital herpes. The annual rate of acquisition of HSV infection was similar among vaccine and placebo recipients (10.7% and 8%, respectively) but was higher in initially seronegative subjects (15.5%) than in those with HSV-1 at entry (5.9%). Eleven (79%) of the 14 HSV infections acquired during follow-up were symptomatic. Vaccination elicited ELISA antibody titers to glycoproteins gD2 and gB2 that were only 10% and 5%, respectively, of titers found in persons with recurrent genital HSV-2 infection. This vaccine failed to provide protection from acquisition of genital HSV infection. The lack of efficacy appears to be related, in part, to the poor immunogenicity of the vaccine.

Adult↗

Cytomegalovirus infection in women attending a sexually transmitted disease clinic.

To evaluate prospectively the relationship between current and past sexual practices and seroprevalence of cytomegalovirus (CMV) in adult women, 1481 women (1101 white, 301 black, 79 other) attending a sexually transmitted disease clinic underwent a standardized interview and genital examination. CMV seroprevalence was higher in black (78%) than in white (59%) women. In logistic regression models that adjusted for age and years of education, CMV seropositivity in white women was associated with younger sexual debut (P = .001), more lifetime sex partners (P = .025), recent new partner(s) (P = .003), and parity (P = .002), and was inversely associated with use of barrier contraception (P = .006). In black women, after adjustment for demographic characteristics, CMV antibody was associated with greater numbers of recent sex partners (P = .007), new sex partners (P = .04), and with cervical infection with Chlamydia trachomatis (P = .05). This study confirms that sexual activity is an important determinant of CMV infection in both white and black women; however, the relative contributions of sexual and nonsexual transmission of CMV apparently vary and require further investigation.

Adolescent↗

Anal human papillomavirus infection among human immunodeficiency virus-seropositive and -seronegative men.

Homosexual men are at high risk of anorectal human papillomavirus (HPV) infection, HPV-related anal cancer, and precancer, conditions known to increase with immunosuppression. The relationship between anal HPV infection, human immunodeficiency virus (HIV) infection, and immunosuppression was studied in homosexual men seen at a sexually transmitted disease clinic. History or presence of warts on rectal examination, and detection of anorectal HPV DNA were each significantly associated with HIV seropositivity after adjusting for age, previous sexual behavior, and cultural or serologic evidence of other sexually transmitted diseases, including those previously identified as risk factors for acquisition of HIV infection. Decreased mean levels of T4 lymphocytes were significantly associated with the detection of anal HPV DNA. Prospective studies are needed to determine incidences of anal HPV infection and cancer among HIV-seropositive and -seronegative mean and to determine the temporal relationship of these infections to one another.

Anus Diseases↗

Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal.

Zidovudine is the only drug currently approved for the treatment of HIV infection. The present recommended doses found to be efficacious in patients with AIDS (200 mg every 4 h) achieve serum zidovudine concentrations greater than 0.267 micrograms/ml (1 mumol/l). Since patients often take zidovudine with food, we have investigated the effect of a liquid high-fat meal on the rate of absorption of zidovudine and on the peak serum concentration achieved. Eight patients received their usual dose of zidovudine (100 mg or 250 mg), with and without a liquid high-fat meal, on two separate study days, in a randomized crossover fashion. Blood and urine samples were collected over a 4-h period. In the absence of food, zidovudine is rapidly absorbed; the time to reach maximal serum concentration (Tmax) was 0.68 (+/- 0.25) h and the mean peak serum concentration (Cmax) achieved was 0.49 (+/- 0.3) micrograms/ml (dose normalized to 100 mg dose). In the presence of a high-fat meal, Tmax was significantly prolonged [1.95 (+/- 0.69) h; P less than 0.05] and the Cmax reduced [0.245 (+/- 0.12) micrograms/ml; P less than 0.05]. This demonstrates that to achieve maximal zidovudine serum concentrations, patients should take this medication on an empty stomach.

Acquired Immunodeficiency Syndrome↗

Plasma viremia in human immunodeficiency virus infection.

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P less than 0.01). Plasma HIV titers ranged from 10(0) to 10(4.3) and rose from a mean of 10(1.4) in asymptomatic patients to 10(2.5) in those with AIDS (P less than 0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titers. Follow-up tests indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious.

AIDS-Related Complex↗

Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group.

A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

Adolescent↗

Transmission of genital herpes by donor insemination.

This report describes a donor in a therapeutic donor insemination program who asymptomatically acquired a primary herpes simplex virus type 2 (HSV-2) infection from his long-standing sexual partner. His fresh semen was used to inseminate two HSV-seronegative recipients; in one a primary HSV-2 infection developed, and in one it did not. Direct evidence of transmission from donor to recipient was documented by restriction enzyme analysis of the HSV-2 isolates obtained from the donor's semen and from the recipient's cervix. Because of the possibility of asymptomatic acquisition and transmission of HSV-2, semen donors and their sexual partners should undergo serologic screening for genital herpes using new, type-specific HSV serologic techniques.

Adult↗

Development of clinically recognizable genital lesions among women previously identified as having "asymptomatic" herpes simplex virus type 2 infection.

STUDY OBJECTIVE: To determine if patients initially identified by history, clinical examination, and serologic status as having asymptomatic herpes simplex virus type 2 infection report clinically recognizable genital lesions after having a detailed instructional session on the clinical signs and symptoms of genital herpes. DESIGN: Prospective follow-up of two groups of women. SETTING: Outpatient clinic of an urban city-county hospital. PATIENTS: Two populations of women were recruited. One group was referred because they had documented asymptomatic genital herpes or were suspected of asymptomatically transmitting genital herpes to a sex partner. The other group was recruited from the hospital's general gynecologic clinic and consisted of women with herpes simplex virus type 2 antibodies who denied a history of genital herpes. INTERVENTION: Patients had a one-on-one interview describing the clinical symptoms of genital herpes. MEASUREMENTS AND MAIN RESULTS: Twelve of nineteen women with herpes simplex virus type 2 antibodies who had documented asymptomatic genital herpes or were suspected of asymptomatically transmitting infection to a sex partner, and 18 of 43 women with herpes simplex virus type 2 antibodies who were recruited from the gynecologic clinic developed clinically recognizable genital lesions during a 5-month follow-up. Symptomatic genital herpes was the most frequent gynecologic complaint identified during follow-up. CONCLUSIONS: Approximately 50% of women with herpes simplex virus type 2 antibodies who do not initially report a history of genital lesions do indeed have clinically symptomatic genital herpes. These women can be accurately counseled and taught to distinguish genital herpes from other genitourinary infections. Identification of symptomatic recurrences and counseling to avoid sexual activity during these episodes may help reduce transmission of genital herpes.

Adolescent↗

Isolation of human immunodeficiency virus from genital ulcers in Nairobi prostitutes.

Recent epidemiologic studies have implicated genital/anorectal ulcer disease as an important cofactor for acquisition and transmission of human immunodeficiency virus (HIV) during sexual intercourse. To better understand the mechanism for the association between genital ulcers and HIV, exudates from 62 genital ulcers of 56 HIV-seropositive prostitutes in Nairobi (Kenya) were cultured for HIV. Twenty-six ulcer cultures could not be evaluated for the presence of HIV because of bacterial or fungal contamination. HIV was isolated from 4 (11%) of the 36 remaining uncontaminated ulcer cultures (2 introital, 1 vaginal, and 1 cervical) from 4 separate women. HIV was isolated from the cervical os from only 2 of the 4 women. HIV p24 antigen was detected in exudate from 1 of the 4 culture-positive ulcers and 0 of 32 culture-negative ulcers. Genital ulcers in seropositive patients should be regarded as potential sources of HIV, which could be important in transmission of HIV during intercourse. Public health measures aimed at controlling sexually transmitted genital ulcer diseases should be an integral part of acquired immunodeficiency syndrome (AIDS) prevention programs.

Adult↗

Comparison of intramuscular recombinant alpha interferon (rIFN-2A) with topical acyclovir for the treatment of first-episode herpes genitalis and prevention of recurrences.

Intramuscular recombinant alpha interferon (rIFN-2A; 9 million IU given for 5 days during a 9-day treatment period) was compared with topical acyclovir in a double-blind, placebo-controlled trial for the treatment of first-episode genital herpes simplex virus (HSV) infection and for subsequent alteration of the frequency of recurrences. rIFN-2A (within 96 h of onset of the first episode) was not superior to topical acyclovir in a well-matched group of 105 patients. The early use of rIFN-2A also did not alter the frequency or severity of genital HSV recurrences within either the first or second 6 months following therapy. Separate analyses by HSV type and by type of infection (primary versus nonprimary) did not change this conclusion. Furthermore, there was significant toxicity associated with rIFN-2A therapy. rIFN-2A is not indicated for the treatment of genital HSV infections.

Acyclovir↗

Comparison of monoclonal antibodies for rapid detection of cytomegalovirus in spin-amplified plate cultures.

Cytomegalovirus (CMV) was detected in 56 of 275 specimens (20%); 50 of 56 (89%) were detected by conventional culture, and 37 (66%) were detected by rapid assay at 72 h with a commercial monoclonal antibody and a pooled monoclonal antibody. Although the two antibodies were equally sensitive at 72 h, the pooled antibody gave a brighter, more easily detected signal. Other viruses were isolated from 9 specimens (3.3%) by conventional culture. Use of rapid assays alone fails to detect slow-growing CMV and non-CMV viral pathogens.

Antibodies, Monoclonal↗

The association between genital ulcer disease and acquisition of HIV infection in homosexual men.

We analyzed the association of herpes simplex virus (HSV) infection and syphilis, the two most common causes of genital ulceration in homosexual men, with human immunodeficiency virus (HIV) infection in 200 men enrolled between 1983 and 1986 into a study evaluating the microbial causes of acute proctitis. Infection with HIV was independently associated with a history of syphilis, serologic evidence of syphilis, a history of HSV infection, and antibody to HSV-2. Antibody to HIV was not associated with a history of other genital infections or with antibody to Chlamydia trachomatis or HSV-1. Similar associations were observed in 111 asymptomatic homosexuals seen for HIV screening. Men who presented with primary HSV proctitis had a lower prevalence of HIV antibody than those with preexisting HSV-2 antibody (44% vs 68%); this suggests that HSV-2 infection antedated HIV infection. These data suggest that genital ulcerative diseases are an important risk factor for the acquisition of HIV infection in homosexual men; measures directed at control of these diseases may reduce the transmission of HIV in this population.

Adult↗

Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes.

A total of 156 patients with frequently recurring genital herpes were enrolled in a randomized, double-blind, one-year trial comparing long-term suppressive and intermittent oral acyclovir therapy with placebo in the management of recurrent genital herpes. Subjects received either suppressive treatment with acyclovir, 400 mg twice daily for one year, and 200 mg five times per day for five days, for short-term treatment of recurrences; intermittent treatment with placebo, twice daily for one year, and oral acyclovir, 200 mg five times per day for five days, for short-term treatment of recurrences; or treatment with placebo, twice daily for one year, and five times per day for five days for short-term treatment of recurrences. Median time to first recurrence was 250 days for the suppressive group, 28 days for the intermittent group, and 23 days for the placebo group (p = 0.001). The median number of days per month with active disease was 0.32 for the suppressive group, 4.18 for the intermittent group, and 4.72 for the placebo group (p less than 0.001), with a median recurrence rate per 30-day treatment period of 0.08 recurrences/patient in the suppressive group, 0.70 in the intermittent group, and 0.74 in the placebo group (p less than 0.001). Median duration of recurrence was 5.0 days in the suppressive group compared with 6.0 days in the combined intermittent acyclovir plus placebo group (p = 0.001), and was reduced from 7.0 to 6.0 days when intermittent acyclovir treatment was compared with placebo treatment (p = 0.05). Daily administration of oral acyclovir for one year is superior to intermittent or placebo treatment in the management of patients with frequently recurring genital herpes.

Acyclovir↗