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Biomedical subjects

M Conant

Publications and source records attributed to M Conant.

At least 19 recordsLinked to original sources
PubMed2006

Poly-L-lactic acid for treating HIV-associated facial lipoatrophy: a review of the clinical studies.

Facial lipoatrophy can be associated with human immunodeficiency virus (HIV), impacting severely on quality of life. Various treatments have been investigated, including poly-L-lactic acid (PLLA). Four studies have investigated the efficacy of PLLA in the correction of HIV-associated facial lipoatrophy. The studies: VEGA, Chelsea and Westminster, APEX002 and Blue Pacific involved 50, 30, 99 and 99 patients, respectively, exhibiting HIV-associated facial lipoatrophy. Follow-up ranged from 24-96 weeks. Measures of treatment efficacy included ultrasound and subjective measures. Significant, long-lasting increases in dermal thickness were recorded and in all four studies, a subjective improvement was reported by patients and investigators in facial appearance and quality of life. Treatment was well tolerated. Small, non-bothersome subcutaneous papules were the only device-related adverse events observed. PLLA represents a promising treatment option for HIV-associated facial lipoatrophy. The procedure requires minimal "downtime" and provides long-lasting results without the need for invasive surgery.

Clinical Trials as Topic↗
PubMed2001

Randomized, double-blind comparison of two nelfinavir doses plus nucleosides in HIV-infected patients (Agouron study 511).

OBJECTIVE: To evaluate the safety and antiretroviral activity of nelfinavir mesylate at two doses as part of a combination regimen in HIV-infected, antiretroviral-naive patients. DESIGN: Phase III, multicenter, double-blind, placebo-controlled trial. PATIENTS AND METHODS: Two-hundred and ninety-seven patients were randomized to one of three treatment groups: nelfinavir 750 mg three times daily (tid), nelfinavir 500 mg tid, or matching placebo, each in combination with open-label zidovudine (ZDV) 200 mg tid and lamivudine (3TC) 150 mg twice daily (bid). Data were analyzed on an intent-to-treat basis. RESULTS: Sixty-seven percent of patients receiving nelfinavir 750 mg tid, and 50% receiving nelfinavir 500 mg tid in combination with ZDV/3TC achieved HIV RNA < 400 copies/ml compared to 7% receiving ZDV/3TC plus placebo (P < 0.001); 55% and 30% of patients in the nelfinavir-containing arms achieved HIV RNA < 50 copies/ml at week 24. This compared with 4% in the placebo-containing arm. For patients continuing nelfinavir treatment (750 mg or 500 mg tid as treated) for a further 6 months, the proportions achieving < 400 copies/ml at week 48 were 75% and 54% (P = 0.001) and < 50 copies/ml 61% and 37%, respectively (P = 0.004). The mean increases from baseline in CD4 cell counts were also durable in patients receiving the triple combination nelfinavir therapy. The range and incidence of adverse events was similar for the two nelfinavir-containing arms, with diarrhea being the most common adverse event. CONCLUSIONS: Nelfinavir plus ZDV/3TC was superior to ZDV/3TC/placebo. In addition, the 750 mg tid nelfinavir dose was better than the 500 mg tid dose. Virologic responses were sustained over 12 months.

Adult↗
PubMed1999

Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group.

BACKGROUND: Kaposi's sarcoma (KS) is the most frequent malignancy in patients with HIV. Given the promise that retinoids show in the treatment of various hyperproliferative skin disorders and in vitro evidence of inhibition of proliferation of KS cells, a randomized, controlled clinical trial was conducted. METHODS AND RESULTS: A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determined by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Of 268 patients entered in the blinded treatment phase of the study (alitretinoin group, n = 134; vehicle group, n = 134), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive response, compared with 24 patients (18%) treated with vehicle gel. Of 184 patients receiving open-label alitretinoin treatment following the blinded phase of the trial, 90 patients (49%) met criteria for a positive response. This superior efficacy of alitretinoin gel over vehicle gel was maintained when the data were adjusted or analyzed for age, race, Kamofsky scores, baseline CD4+ lymphocyte counts, number of raised lesions at baseline, and aggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies. Most adverse events were mild to moderate in severity, limited to the application site, and reversible on reduction in frequency or suspension of application. Relatively few patients (7%) discontinued alitretinoin therapy because of to related adverse events. CONCLUSIONS: The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoin 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS lesions.

AIDS-Related Opportunistic Infections↗
PubMed1999

An interactive, computer-based program to educate patients about genital herpes.

BACKGROUND AND OBJECTIVES: Education and counseling constitute a substantial portion of management of patients with genital herpes. Innovative methods for education about genital herpes are needed. GOAL: To test the ability of an interactive, computer-based program to educate patients about genital herpes. STUDY DESIGN: Persons seeking care at five urban offices were asked to participate. A knowledge test about genital herpes was administered before and after participation. Participants' satisfaction was assessed with a questionnaire. RESULTS: Four hundred thirty-five participants enrolled, and 428 completed the herpes knowledge test. Of six questions evaluated, a statistically significant increase in the proportion of correct answers was noted on five of six questions. Fifty-one percent of participants answered all the questions correctly after the program, compared with 39% before the program. Satisfaction with the program was very high. CONCLUSIONS: Innovative, computer-based programs can provide education and assist in the management of chronic sexually transmitted infections.

Adolescent↗
PubMed1998

A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection.

A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-1 protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entered an open-label extension that allowed for the addition of nucleoside inhibitors of reverse transcriptase and dose escalation to maintain durability. The drug was well-tolerated and demonstrated robust antiviral activity, with demonstrable superiority of the 750 mg and 1000 mg three times daily regimens. Thirty subjects who continued to receive therapy at 12 months attained a persistent 1.6 log10 reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/mm3. Studies of viral genotype and phenotype after virus rebound revealed that the initial active site mutation allowing for nelfinavir resistance is mediated by a unique amino acid substitution in the HIV-1 protease D30N, which does not confer in vitro phenotypic cross-resistance to the currently available protease inhibitors.

Adult↗
PubMed1998

A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs.

Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors can efficiently suppress human immunodeficiency virus (HIV) replication, but the emergence of drug-resistant variants correlates strongly with therapeutic failure. Here we describe a new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested reverse transcription-PCR. The pool of PR-RT-coding sequences is then cotransfected into CD4+ T lymphocytes (MT4) with the pGEMT3deltaPRT plasmid from which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are deleted. Homologous recombination leads to the generation of chimeric viruses containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The susceptibilities of the chimeric viruses to all currently available RT and/or PR inhibitors is determined by an MT4 cell-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based cell viability assay in an automated system that allows high sample throughput. The profile of resistance to all RT and PR inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Current clinical issues in the management of herpes simplex virus infections in patients with HIV.

BACKGROUND: A recent study done in Baltimore showed HSV-2 seroprevalence of 81% among 64 HIV-positive homosexual or bisexual men. OBJECTIVE: Our purpose was to examine HSV-2 as a risk factor for acquiring HIV infection, as well as to explore the possibility that acyclovir, an agent that inhibits the replication or infectivity in herpesviruses, might have a survival benefit to patients with HIV infection. METHODS: Studies were undertaken among HIV-positive patients to see if concomitant treatments including acyclovir offered a survival benefit. RESULTS: A Multicenter AIDS Cohort Study held at four university-affiliated clinics and two landmark analyses demonstrated that acyclovir offered a significant survival advantage for HIV-positive patients. Another study had less conclusive results. CONCLUSION: Enough evidence of a survival benefit in HIV-positive patients on long-term acyclovir therapy warrants consideration of long-term prophylactic therapy with suppressive doses of acyclovir as routine intervention for HIV-positive patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Sustained-release morphine sulfate in the management of pain associated with acquired immune deficiency syndrome.

Sustained-release morphine (SRM) was studied in patients with acquired immune deficiency syndrome (AIDS)-related chronic pain. Outpatients and inpatients with AIDS-related pain were studied for 3-18 days in an open-label prospective survey. Patients were stratified according to prior opioid analgesic use for the purposes of initiating and titrating SRM, which was administered at a 12-hr interval. Immediate-release morphine (IRM) was offered every 2 hr as needed for supplemental analgesia at one-quarter to one-third of the 12-hourly SRM dose. Pain intensity (PI), quality of life (QL), acceptability of therapy (AT), side effects, safety, and morphine usage were evaluated. Of 44 patients enrolled, 40 (91%) were evaluable for intent-to-treat analysis, and 24 (55%) completed the study. PI decreased by 50% (from severe to mild-moderate) in the intent-to-treat patients and by 65% (from severe to mild) in the completed patients. QL was fair to good in 80% and poor in 20% of both groups. AT was good to excellent in 78% of the intent-to-treat and in 96% of the completed patients. Of 61 adverse events reported, 61% required intervention, and 92% were resolved. Total morphine dose remained stable while IRM dosage and frequency of use significantly decreased with escalation of the SRM dose. A significant reduction in PI was achievable with SRM in a variety of painful conditions experienced by AIDS patients, with limited or manageable side effects in most. This study supports the usefulness of opioid analgesia for severe pain in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Frequent presence of a novel herpesvirus genome in lesions of human immunodeficiency virus-negative Kaposi's sarcoma.

While Kaposi's sarcoma (KS) is extremely common in homosexual men infected with human immunodeficiency virus (HIV), it is also found in several clinical settings in which HIV infection is absent. Recently, sequences from the genome of a novel member of the herpesvirus family have been identified within KS biopsies in the AIDS-associated form of the disease. The presence of these sequences was sought in 6 cases of HIV-negative KS, including 4 cases of endemic KS from Africa, and was found in 5 of the 6. These findings strengthen the association between infection with this virus and the development of KS and argue against the notion that this association is simply the result of opportunistic superinfection of profoundly immunodeficient hosts.

Adult↗
PubMed1995

Human analog tests of the sixth stage of object permanence.

Two adult cats were tested on multiple invisible displacement. A dowel was established as a secondary reinforcer and hidden in a manner similar to that used to assess the culmination of sensorimotor intelligence in human infants. Three other cats were tested on single invisible displacement, a simpler version of the task. For human infants, this task is used to assess the beginning of mental representation in the sixth and last stage of sensorimotor intelligence. The cats' searches on these tasks were consistent with representation of an unsensed object and fully developed sensorimotor intelligence.

Animals↗
PubMed1994

Zidovudine improves psoriasis in human immunodeficiency virus-positive males.

BACKGROUND AND DESIGN: Patients with human immunodeficiency virus (HIV) infection can develop severe psoriasis, which is difficult to treat using conventional therapy. Anecdotal case reports have suggested that administration of zidovudine can improve psoriasis in the HIV-infected patient. An open-label study was conducted to determine the safety and effectiveness of zidovudine therapy in 24 patients with HIV-associated psoriasis and to correlate response with laboratory and clinical variables. RESULTS: Of 19 evaluable patients, 90% had either partial (58%) or complete (32%) improvement of their HIV-associated psoriasis during zidovudine therapy. Greater than 75% reduction in the body surface area involved was positively associated with antigenemia and an age younger than 30 years. CONCLUSIONS: Zidovudine therapy, at a dosage of 1200 mg/d, appears to be beneficial in the treatment of HIV-associated psoriasis, although long-term relapses occurred and the associated arthritis did not improve.

Adult↗
PubMed1992

Recombinant alpha-2 interferon gel treatment of recurrent herpes genitalis.

Topical recombinant alpha-2 interferon treatment of recurrent genital herpes was studied in a randomized, double-blind, placebo controlled clinical trial. Three hundred and eighty-seven patients were treated at eight study centers with either interferon gel or placebo four times daily for four days. Interferon therapy caused a 26% decrease in the duration of viral shedding. For male patients, there were also significant decreases in the time to crusting (17%) and duration of pain (34%) and itching (21%). For patients with recurrent genital herpes, treatment with topical interferon was found to be effective in decreasing the duration of viral shedding and, for males, pain, itching and time to crusting.

Administration, Cutaneous↗