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.

Anonymous HIV testing using home collection and telemedicine counseling. A multicenter evaluation.

BACKGROUND: Home human immunodeficiency virus (HIV) testing has been proposed as an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV-1) home test systems, these concerns have not to our knowledge been previously studied. OBJECTIVE: To evaluate the safety and efficacy of the Home Access Health Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1 testing with venous blood. METHODS: A total of 1255 subjects were studied prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics using intent-to-treat analysis. Subjects were provided a home collection kit (Home Access Health Corp) to collect their own finger-stick blood spot samples for laboratory analysis. Subjects received pretest counseling by telephone and their comprehension was subsequently assessed. Subject-collected blood spot samples were compared with professionally drawn blood spot samples for adequacy (sufficient for completing the Food and Drug Administration-endorsed testing) and with venous samples for accuracy. Subjects called 3 days later for anonymous results and posttest counseling. Device safety was evaluated based on adverse events incidence. Subject comprehension of HIV information was measured. RESULTS: Subject-collected blood spot sample results were in complete agreement with venous blood sample results, demonstrating 100% sensitivity and 100% specificity compared with venous controls. Ninety-eight percent of subjects obtained testable blood spot specimens compared with phlebotomists. Following pretest counseling, subjects answered 96% of HIV risk questions correctly. There were no significant adverse events. CONCLUSION: Anonymous HIV-1 home collection kits with pretest and posttest telephone counseling can provide a safe and effective alternative to conventional venous HIV-1 antibody testing.

Persistent stress as a predictor of genital herpes recurrence.

BACKGROUND: Results of several studies suggest that psychological stress and negative mood can trigger genital herpes recurrences, but results are inconsistent. OBJECTIVE: To determine whether short-term or persistent psychological stress or specific negative moods are predictive of genital herpes recurrences in women. METHODS: A prospective cohort study followed up participants for 6 months using weekly assessments of stress and mood, monthly assessments of life change events, and diary reports of genital herpes recurrences confirmed by medical examination when feasible. The community sample consisted of 58 women, aged 20 to 44 years, with a 1- to 10-year history of visible genital herpes recurrence and at least 1 recurrence in the previous 6 months. RESULTS: Persistent stress predicted recurrence in the subsequent week (odds ratio, 1.08 per unit increase in stress; 95% confidence interval, 1.01-1.15; P=.03). After adjusting for recurrence in the previous week, the more weekly persistent stress reported, the greater the likelihood of recurrence the following week. Also, an increased recurrence rate occurred after the month during which participants experienced their highest levels of anxiety (P =.03). There were no significant associations between recurrence and short-term stress, life events, depressive mood, anger, or phase of menstrual cycle. CONCLUSIONS: Persistent stressors and highest level of anxiety predicted genital herpes recurrence, whereas transient mood states, short-term stressors, and life change events did not. Women with herpes can be reassured that short-term stressful life experiences and dysphoric mood states do not put them at risk for increased outbreaks of recurrent genital herpes.

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.

Maintenance of CD4+ cells by thymopentin in asymptomatic HIV-infected subjects: results of a double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of thymopentin in HIV-infected patients who had not yet developed AIDS. DESIGN: Patients were stratified into asymptomatic or symptomatic groups and randomized to receive either thymopentin (50 mg) or placebo, subcutaneously, double-blind for 24 or 52 weeks, three times a week. SETTING: Patients were enrolled at three sites (two hospital clinics and one private practice). PATIENTS: Of 91 HIV-seropositive patients (52 asymptomatic and 39 symptomatic) from whom HIV could be isolated from peripheral blood, 45 were enrolled for 24 weeks and 46 for 52 weeks of double-blind evaluation. MAIN OUTCOME MEASURES: Virological, immunological and clinical evaluations were performed before and during treatment. RESULTS: Thymopentin-treated asymptomatic patients had more CD4+ cells, as demonstrated by a greater area under the percentage CD4+ cells curve (P = 0.03) and a shorter median time to a 20% increase in percentage of CD4+ cells (P = 0.04) in the first 24 weeks, with similar trends in the 52-week study. By 24 weeks no asymptomatic thymopentin-treated and two placebo-treated patients (9.1%, Kaplan-Meier estimate) had progressed to constitutional symptoms (P = 0.12; two-tailed Wilcoxon-Gehan test), with only one further progression in a placebo-treated patient in the subset followed for 52 weeks. Symptomatic patients receiving thymopentin or placebo were similar in both CD4+ cell levels and disease progression (two progressions to AIDS in each group). No serious adverse effects attributable to thymopentin were observed. CONCLUSIONS: These results, if confirmed, indicate that thymopentin, by maintaining CD4+ cells, could slow or arrest immune decline and consequent disease progression at the asymptomatic stage of HIV infection.

A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group.

OBJECTIVE: To assess the safety of imiquimod, an immune response modifier, in the topical treatment of external anogenital warts in HIV-infected patients. SETTING: Clinical sites in the United Kingdom (eight) and the United States (five). DESIGN: A prospective, randomized, double-blind, vehicle-controlled study of imiquimod 5% cream or vehicle applied for 8+/-2 h three times per week for a maximum of 16 weeks in HIV-seropositive males (n = 97) and females (n = 3) aged 18 years or more with clinically diagnosed external anogenital warts, CD4 T lymphocyte count of > or = 100 x 10(6) cells/l and Karnofsky score > or = 70. MAIN OUTCOME MEASURES: Safety was assessed through the incidence and severity of local skin reactions and other adverse events, and through clinical laboratory tests. Wart clearance was documented by two-dimensional measurements of warts and by photography. RESULTS: Among the patients treated with imiquimod (n = 65) and vehicle (n = 35), the most common local skin reaction was erythema, (41.9 and 26.7%, respectively) and the incidence of patients reporting at least one adverse event was 69.2 and 65.7%, respectively. No clinically meaningful differences or changes in laboratory values were observed between treatment groups, nor were drug-related adverse effects observed in regard to HIV disease. While there was no significant difference between treatment groups in the number of patients who totally cleared their baseline warts (imiquimod 11% versus vehicle 6%, P = 0.488), more imiquimod-treated patients experienced a > or = 50% reduction in baseline wart area (38% versus 14%, P = 0.013). CONCLUSION: Most local skin reactions were mild and no adverse effects on HIV disease were observed. Topically applied imiquimod 5% cream reduced wart area and may have clinical utility in treating external anogenital warts in some HIV-infected patients.

Speculations on the viral etiology of acquired immune deficiency syndrome and Kaposi's sarcoma.

The acquired immune deficiency syndrome (AIDS) appeared in the United States in late 1978 and has spread at an epidemic rate through the four major coastal cities of this country. The disease appears to show the same epidemiologic distribution as hepatitis B virus infection, and for this reason, most investigators feel that this new disease is caused by a blood-borne sexually transmitted virus. A number of viral agents have been suggested as the cause of AIDS, but to date, no virus has been consistently isolated. The most likely candidate is a retrovirus that has recently been introduced into the human population and has found its way into two extremely high-risk groups, namely, promiscuous male homosexuals and intravenous drug abusers. The relationship between Kaposi's sarcoma and cytomegalovirus is still unclear, but evidence is mounting that cytomegalovirus may be the agent that initiates this multifocal malignancy. Multiple factors must be involved in this process. It is known that some immunosuppressed individuals develop Kaposi's sarcoma, which completely resolves when the immunosuppression is reversed; however, in individuals with classical Kaposi's sarcoma, the profound degree of helper T-cell depression that characterizes the acquired immune deficiency syndrome is not seen.

Basement membrane and connective tissue proteins in early lesions of Kaposi's sarcoma associated with AIDS.

Nearly one-third of all young homosexual men diagnosed as having acquired immune-deficiency syndrome (AIDS) develop a disseminated form of dermal Kaposi's sarcoma (KS). Although the histogenesis of KS cells is unclear, certain evidence suggests that the aberrant cells are of endothelial derivation. We have examined the presence and distribution of connective tissue-specific and basement membrane-specific macromolecules by indirect immunofluorescence and immunoperoxidase staining of frozen sections in early cutaneous lesions of KS from individuals with AIDS. The KS cells typically line the spaces between collagen bundles of the reticular dermis. When stained for the connective tissue-specific glycoprotein fibronectin, all Kaposi's sarcoma lesions showed an intense staining pattern, revealing a complex array of linear deposits of antigen that outlined the exterior surface of the collagen bundles. Antibodies to laminin and type IV collagen, both basement membrane-specific macromolecules, produced an intense staining pattern similar to that found with the anti-fibronectin antiserum, indicating that all 3 antigens are closely codistributed. In contrast, antibodies to type I collagen, the major collagen of the dermis, uniformly stained the collagen bundles in the KS lesions and in the normal control skin. Antiserum to factor VIII-associated antigen, an antigen specific to blood vascular endothelium, frequently stained the KS lesions but the staining pattern was diffuse and of variable intensity. The results suggest that KS cells are derived from the endothelium of the blood microvasculature and maintain their secretory phenotype of secreting basement membrane-specific macromolecules.

Efficacy of desciclovir in the treatment of Epstein-Barr virus infection in oral hairy leukoplakia.

The efficacy of desciclovir, an analog of acyclovir, in eliminating lesions of oral hairy leukoplakia (HL) and suppressing Epstein-Barr virus (EBV) infection was evaluated in a double-blind, placebo-controlled study of 14 patients. Patients were randomized to receive either the active drug, 250 mg three times a day for 14 days, or placebo. In all eight patients receiving desciclovir, lesions of HL were either completely resolved or significantly reduced during the treatment period, whereas lesions in patients receiving placebo showed no change. The histological features of HL were significantly diminished in patients on desciclovir, and cytochemical, in situ hybridization, and ultrastructural studies showed that EBV infection was eliminated or dramatically reduced in the desciclovir group only. Four patients on desciclovir reported side effects, but none required withdrawal from the study. The reappearance of HL in all eight subjects on desciclovir within 1-4 months after therapy was discontinued suggests the need for additional study.

Chemotherapy in advanced Kaposi's sarcoma. Implications for current cases in homosexual men.

Kaposi's sarcoma has recently appeared in an aggressive form in young, previously healthy, homosexual men. The disease in these patients corresponds most closely to disseminated Kaposi's sarcoma common in areas of Africa. This and the underlying acquired immune deficiency in the current patients in the United States affect the choice of appropriate therapy. Because Kaposi's sarcoma in these patients is rapidly progressive, it often requires aggressive systemic therapy, but this can be difficult given the patients' susceptibility to opportunistic infections. Reports from Africa suggest that Kaposi's sarcoma is very responsive to several chemotherapeutic agents, but these data must be interpreted cautiously because of problems in study design and differences between cases in Africa and the United States. This report reviews the clinical classification of Kaposi's sarcoma and the reported results of chemotherapy in patients with advanced disease. Implications of this experience in the treatment of recent cases in the United States are discussed.

Episodic twice-daily treatment for recurrent genital herpes.

A new dosage regimen of orally administered acyclovir, 800 mg twice daily for five days, for the treatment of recurrent genital herpes was compared with the standard dosage of 200 mg given five times per day. A double-blind study of 157 patients was used to evaluate the safety and efficacy of both regimens. The new regimen was well tolerated, more convenient, and as effective as the standard dosage. In male patients, the new regimen may be more effective than the standard regimen of 200 mg given five times per day to treat lesions that are already present.

Prolonged continuous versus intermittent oral acyclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection.

In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.

Analysis of human KS biopsies and cloned cell lines for cytomegalovirus, HIV-1, and other selected DNA virus sequences.

Investigation into a possible role of several human viruses, including human cytomegalovirus (HCMV), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV) in the pathogenesis of Kaposi's sarcoma (KS) has resulted in the lack of an association of these viruses in KS biopsy and cloned KS cell line specimens. Since nearly all patients with KS, including those with HIV-associated KS, have a high incidence of HCMV infection, HCMV has been proposed to be etiologically associated with KS. Moreover, our previous studies showed the retention of HCMV morphological transforming region II (mtrII) in both transformed and tumor-derived cell lines. As a result, we focused on the nucleic acid hybridization analysis of both KS biopsies from AIDS patients as well as cloned KS endothelial cell lines for HCMV mtrII sequences. We also analyzed KS biopsy and KS cloned cell line specimens for HIV-1, HBV, HHV6, and EBV sequences, since these viruses have also been implicated in the etiology of KS. In one set of experiments, Southern blot analysis revealed the presence of HCMV mtrII sequences in two of six KS biopsies; in other experiments, HBV sequences were found in one of seven KS biopsies. No hybridization in any biopsy tissue was detected for HIV-1 DNA sequences. The analysis of six independently derived cloned KS cell lines was next studied. All these lines were negative for hybridization to the HCMV mtrII transforming fragment as well as to subgenomic fragments of HHV6 and EBV.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Survival in the elderly with acute leukemia.

The natural history of acute leukemia in the elderly is not well understood. There is disagreement about the value of treatment other than by supportive measures. In this study, the survival predictive power of 9 variables was analyzed in 103 patients aged 70 or older for whom a bone-marrow cytologic diagnosis of acute leukemia had been made at a referral hospital during the 30-year period, 1947--1976. When given, treatment was uniformly conservative. Blood leukocyte and platelet counts and hematocrit values at the time of diagnosis, sex, treatment, and the calendar year of diagnosis were significant (P less than 0.01) predictors of survival duration. Initial hematologic measurements, presumably reflecting the degree of leukemic cell infiltration of the bone marrow, were the strongest predictors of survival, whereas leukemic cell type had no predictive power. Survival increased significantly (P less than 0.01) during the 30-year period of the study, possibly more attributable to improved supportive care than to specific antileukemic therapy. Apparently survival is at least partly determined at the time of diagnosis, and conservative therapy often may be beneficial rather than detrimental.

Herpes zoster ophthalmicus and acquired immune deficiency syndrome.

Acquired immune deficiency syndrome (AIDS) is a recently recognized disease characterized by abnormalities in cell-mediated immunity that predispose affected persons to severe opportunistic infections and unusual malignant neoplasms. We describe four cases of herpes zoster ophthalmicus in four previously healthy homosexual men. Two had signs and symptoms consistent with AIDS, and two had signs and symptoms of a lymphadenopathic syndrome associated with AIDS. We suggest that underlying AIDS be considered in young, healthy persons with herpes zoster ophthalmicus and no known cause of immunosuppression.

Hematologic manifestations in homosexual men with Kaposi's sarcoma.

Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Perioral leukoderma simulating vitiligo from use of a toothpaste containing cinnamic aldehyde.

Perioral leukoderma simulating vitiligo developed in a 25-year-old woman. A patch test to cinnamic aldehyde was positive; depigmentation was observed at the patch test site three months after initial application. No changes in pigmentation occurred from a concomitant allergic patch test reaction to neomycin sulfate; only hyperpigmentation occurred at the site of an irritant patch test reaction to nonanoic acid. A toothpaste containing cinnamic aldehyde was implicated; perioral hypopigmentation resolved when a toothpaste without cinnamic aldehyde was substituted. A repeated patch test to cinnamic aldehyde again showed depigmentation at the patch test site three months after application.

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.

Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group.

BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3-month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity.