Chronic hypertrophic acyclovir-resistant genital herpes treated with topical cidofovir and with topical foscarnet at recurrence in an HIV-positive man.
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Biomedical subjects
Publications and source records attributed to M Cusini.
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The efficacy of imiquimod in the treatment of external genital warts in HIV positive subjects was compared to a group of patients with normal immune function. Imiquimod 5% cream was applied by patients three times a week until resolution for a maximum of 16 weeks. Assessment for response and the occurrence of side effects was performed every four weeks. Thirty-one per cent of 75 HIV positive patients achieved a complete clearance, a partial response was obtained in 24% of subjects while in 45% we observed no clinical response. In the control group a total clearance was obtained in 62% of subjects, a partial response in 24% and no response in 14%. Recurrences occurred in 4/23 HIV patients and 2/31 immunocompetent patients within three months of follow-up. Side effects were minor to moderate. We conclude that imiquimod 5% cream has an acceptable efficacy and safety on HIV patients.
Topical immunomodulators (TIMs) include both immunostimulatory and immunosuppressive agents. Newer immunostimulatory compounds such as imidazoquinolines (e.g. imiquimod) act by cytokine secretion from monocytes/macrophages (interferon-alpha, interleukin-12, tumour-necrosis factor-alpha), leading to a Th1-dominance and cell-mediated immunity. This immune milieu has been clinically used to treat viral infections such as human papillomavirus (condyloma and common warts), herpes simplex virus and mollusca in immunocompetent and immunosuppressed patients.
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Genital herpes is the result of infection by herpes simplex virus type 2 (HSV-2) and, to a lesser extent, HSV-1. Recent years have seen a rise in the prevalence of genital HSV infection in both industrialized and developing countries. The main factors attributed to the spread of HSV infection include asymptomatic virus shedding, and under-recognition and under-diagnosis of the disease. At the level of the individual patient, genital herpes is associated with significant psychosocial morbidity and complications such as neonatal herpes, the result of transmission of HSV from mother to baby. HSV-2 infection is also implicated in the transmission and acquisition of human immunodeficiency virus (HIV). As genital HSV infection has substantial public health implications, increased awareness of the disease and its prevalence, together with better use of diagnostic tests, may be one step towards more effective management and infection control.
The SDF-1 3'A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3'A/3'A genotype and accelerated disease progression was evident among seroconverters (n=319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4(+) T cell counts <200 was observed. The relative hazards for SDF1-3'A/3'A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P=.0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P=.0001), for time from CD4(+) T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3'A/3'A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4(+) T lymphocytes.
BACKGROUND: Mycoplasma genitalium is regarded as a potential pathogen of the human urogenital tract based on prevalence findings of several European studies. GOAL: To determine the prevalence of M genitalium in urethral specimens of symptomatic patients with nongonococcal urethritis and from asymptomatic patients attending a sexually transmitted disease clinic in Milan, and to verify the clinical efficacy of M genitalium eradication by antibiotic treatment. STUDY DESIGN: From May 1998 to late April 1999, a routine analysis for M genitalium by DNA amplification (polymerase chain reaction) was performed in patients attending the Institute of Dermatological Science in Milan. The authors examined urethral swabs from 178 symptomatic and 23 asymptomatic males. M genitalium-positive patients were clinically and microbiologically tested after treatment with either doxycycline or azithromycin. RESULTS: Among males with nongonococcal urethritis, M genitalium was detected in 14.0% of patients as the only agent; in 15.1% of patients in association with Chlamydia trachomatis and/or Ureaplasma urealyticum; and in 1 asymptomatic patient. In all symptomatic M genitalium-positive patients, antibiotic treatment eradicated the infection and cured clinical symptoms. CONCLUSION: These data reveal the high prevalence of M genitalium in symptomatic patients, the rarity of asymptomatic carriers, the high susceptibility to antibiotic treatment, and the clinical efficacy of M genitalium eradication. Moreover, data confirm the etiologic role of M genitalium in inflammatory processes of the human urogenital tract in the Mediterranean area.
BACKGROUND AND OBJECTIVES: An increased prevalence of herpes simplex virus type 2 (HSV-2) infection has been recently observed in industrialized countries. GOAL: To determine HSV-2 seroprevalence in a high-risk population in Italy. STUDY DESIGN: A cross-sectional study was performed to ascertain the HSV-2 prevalence among 919 persons attending an STD clinic in northern Italy. A HSV-2-specific glycoprotein G-2-based immunoglobulin G enzyme-linked immunoabsorbent assay (Gull/Meridian ELISA; Meridian Diagnostics, Cincinnati, OH) was used and validated against Western blot analysis. RESULTS: A prevalence of 24.6% was found without differences between males and females. Seroprevalence increased with age and number of partners during the previous year. Compared with Western blot analysis, the Gull/Meridian ELISA showed a sensitivity of 91.9% and a specificity of 98%, and positive and negative predictive values of 93.9% and 97.4%, respectively. CONCLUSION: This is the first Italian survey of HSV-2 infection conducted with a properly validated, Food and Drug Administration-approved, type-specific serologic method in a high-risk population. It is likely that between one to three million adults are infected with HSV-2.
This randomized, double-blind, placebo-controlled, phase II/III study was designed to evaluate safety, immunogenicity, and efficacy of an active anti-interferon-alpha (anti-IFN-alpha) vaccine in asymptomatic HIV-1-infected patients. The active immunization was aimed at inducing anti-IFN-alpha antibodies to counteract IFN-alpha overproduction. In all, 242 patients, recruited between December 1995 and July 1996 in eight centers in Europe and Israel, with CD4+ counts from 100 to 634 cells/mm3 who were receiving or not receiving antiretroviral therapy (including protease inhibitors) were randomized to receive either anti-IFN-alpha vaccine or placebo. The anti-IFN-alpha immunization regimen consisted of three priming injections delivered intramuscularly at 1-month intervals in a water-in-oil emulsion of inactivated recombinant IFN-alpha-2b (i-IFN-alpha) followed by intramuscular booster injections of i-IFN-alpha adsorbed onto calcium phosphate every 3 months. Immunogenicity to vaccine was defined as an increase of anti-IFN-alpha antibody level of more than twofold the preimmunization value. Clinical progression, changes in antiretroviral treatment, and decrease of CD4+ counts to <200 cells/mm3 were considered endpoints for efficacy evaluation. Contrary to our previous experience, in which six to seven oil priming injections induced a >90% response rate, the three oil-adjuvanted injections in this trial were suboptimal because only 40 of 122 vaccinees (33%) had raised anti-IFN-alpha antibody following immunization. In vaccinees, both antibody responders (AbRV) and nonresponders (AbNRV), the tolerance to the vaccine was good and was without evidence of significant safety concerns. During the course of the trial, 62% of vaccine responders, 64% of nonresponders, and 63% of placebo patients elected to add protease inhibitor-containing regimens as new treatment guidelines were established, resulting in a marked decrease in clinical and laboratory progression such that the expected endpoints of the study could not be achieved and further follow-up was halted. Despite the unexpectedly low immunogenicity and fewer than expected endpoints, anti-IFN-alpha vaccine recipients, in comparison with placebo recipients, showed a lower rate of disease progression, nonelective treatment changes, and/or CD4+ count decrease to <200 cells/mm3, but the difference was not statistically significant. Nevertheless, the subgroup of patients immunized to IFN-alpha who experienced a rise in anti-IFN-alpha antibodies had a significantly lower rate of occurrence of HIV-1-related events and of any combination of the endpoints compared with those of either placebo patients or vaccinees who failed to develop anti-IFN-alpha antibodies, the latter two groups behaving similarly. Further studies of this approach are warranted because these data suggest a beneficial effect of this adjuvant approach.
OBJECTIVE: Presentation of a case of disseminated histoplasmosis, observed in a non-endemic area, in which cutaneous lesions and fever were the dominant clinical signs of the infection. CASE: A 54-year-old homosexual man with acquired immunodeficiency syndrome (AIDS) related Kaposi's sarcoma presented with cutaneous lesions and fever due to disseminated histoplasmosis. The patient was successfully treated with itraconazole 200 mg/day. He died after 8 months from AIDS dementia complex: disseminated histoplasmosis relapse was not observed. CONCLUSION: The case shows that infection with Histoplasma capsulatum must be considered by dermatologists in HIV/AIDS patients, even in non-endemic areas.
BACKGROUND: Pharmacological treatment of depression in HIV-infected patients has been found to be effective. This study assessed the efficacy and feasibility of treatment with fluoxetine and the best method of administering the drug to patients with HIV infection. METHODS: Sixteen seropositive and 16 seronegative patients, equally matched for age and sex, who had Hamilton Rating Scale for Depression scores of at least 16 and who received at least 20 mg/d of fluoxetine for 8 weeks were studied. RESULTS: Depression was alleviated in both groups. However, improvement in the seropositive patients occurred later. INTERPRETATION: The results confirm the effectiveness of fluoxetine in treating depression in people with HIV infection. The lack of adverse effects makes this treatment particularly suitable, especially because seronegative people take longer to respond to treatment.
A retrospective study was performed to assess the efficacy and low mucosal toxicity of intracavitary contact X-ray therapy (ICRT), a proposed treatment of small/medium sized lesions of oral HIV-associated Kaposi's sarcoma (HIV-KS). Twenty-six patients with histologically confirmed oral HIV-KS underwent ICRT in the period 1986-1995. No patient received antiblastic or interferon therapy during the radiotherapy or follow-up periods. ICRT was performed according to the usual technical modalities of contact X-ray therapy, but the end of the source of ionizing radiations was introduced into the oral cavity. The total doses administered ranged from 10 to 50 Gy per field, in one or two weekly fractions of 5 Gy each. The follow-up ranged from 1 to 44 months (mean 7.5 months). Complete remission was obtained in 20 cases (76.92%), partial remission in 6 (23.08%) and relapse in one case (3.84%). Pain was relieved in all cases. Mucosal reaction was mild and did not result in any interruption of treatment. Our data suggest that ICRT is an effective and well tolerated treatment. It can be used in the management of oral HIV-KS instead of external radiotherapy, provided that the size and the location of the lesions and the conformation of the palate are suitable to this technique.
We studied the effects of acetyl-L-carnitine on pain in 16 HIV+ patients affected by painful distal symmetrical neuropathy. Patients were treated with 0.5-1 gr per day of acetyl-L-carnitine either i.m. or i.v. for 3 weeks. Pain intensity was measured before and after the treatment by the Huskisson's analogic scale. Ten patients (62.5%) reported an improvement of symptoms, five patients (31.25%) were unchanged, one patient worsened. The results of this open study show that acetyl-L-carnitine can have a role in the treatment of pain in distal symmetrical polyneuropathy related to HIV infection. However, further double-blind, placebo-controlled studies are needed to confirm these preliminary results.
BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.
OBJECTIVE: AIDS frequently associates with certain malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL), and anogenital neoplasia. In this study we aimed to define the frequency of infection by human herpesvirus (HHV)-8 throughout the spectrum of AIDS-related neoplasia in Europe. DESIGN: A tumour panel representative of the distinct types of AIDS-related neoplasms was tested for the presence of HHV-8 DNA sequences. Autologous uninvolved tissues were also tested in selected cases. METHODS: The presence of HHV-8 DNA sequences was assayed by a combination of polymerase chain reaction followed by oligohybridization and Southern blot hybridization of genomic DNA with an HHV-8-specific probe. RESULTS: HHV-8 sequences were detected in 100% of AIDS-related Kaposi's sarcoma (all 35 cases). Among AIDS-related NHL, HHV-8 sequences selectively clustered with body-cavity-based lymphomas (BCBL; all three cases), although they were consistently negative in small non-cleaved cell lymphomas (none in 18 cases), diffuse large cell lymphomas (none in seven), or anaplastic large cell lymphomas (none in three). No HHV-8 sequences were found in cases of anogenital neoplasia (out of 14) or Hodgkin's disease (out of three). HHV-8 DNA sequences were also positive in the uninvolved skin of all six AIDS-related Kaposi's sarcoma patients, but not in the circulating lymphocytes of a BCBL patient. Positivity for HHV-8 sequences occurred in patients belonging to all major AIDS risk categories. CONCLUSIONS: These data confirm that HHV-8 sequences associate at high frequency with selected types of AIDS-related neoplasia, namely Kaposi's sarcoma and BCBL, although they are consistently absent in other types of AIDS-NHL and AIDS-related anogenital neoplasia.
Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-alpha (IFN-alpha) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-alpha overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-alpha levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-alpha immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 micrograms formalin-inactivated recombinant IFN-alpha-2b (iIFN-alpha) followed by intramuscular injections of 250 micrograms iIFN-alpha adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-alpha-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-alpha titers, while nonprogression of IFN-alpha-immunized patients was associated with decreased levels of circulating IFN-alpha.