Willy Rozenbaum

Efficacy and Tolerance of Intravitreal Ganciclovir in Cytomegalovirus Retinitis in Acquired Immune Deficiency Syndrome

Forty-four patients with acquired immune deficiency syndrome with cytomegalovirus (CMV) retinitis (64 eyes) intolerant of or refusing systemic antiviral therapy received 710 intravitreal injections of ganciclovir at the dosage of 400 micrograms per injection. The patients were followed for a mean period of 9 weeks. Induction therapy consisted of two injections a week until healing. Maintenance therapy consisted of one injection a week until relapse. All but 1 of 53 induction courses led to cicatrization, after a mean of 6.6 injections. In 54 maintenance courses, the 8-week relapse rate was 53%. During intravitreal therapy, involvement of the fellow eye occurred in 11% of the patients and CMV infection developed in a nonocular site in 16% of the patients. Five retinal detachments and two intravitreal hemorrhages occurred. No endophthalmitis or cataract was noted. Intravitreal ganciclovir appears to be a safe and effective alternative in patients intolerant of intravenous anti-CMV drugs.

Evidence for changes in adrenal and testicular steroids during HIV infection

The serum levels of cortisol, progesterone, 17α-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (δ4), testosterone (T), estrone, and estradiol of HIV + men and HIV- men were determined by radioimmunoassay. The cortisol, 17α-hydroxyprogesterone, and estrone levels of all HIV+ subjects were 35–55% (p < 0.01), 25–90% (p < 0.01), and 30–50% (p < 0.01) higher, respectively, than those of controls. Androgen levels were very high in Centers for Disease Control (CDC) groups II and III of HIV infection (DHEA, 85%, p < 0.01; δ4, 60%, p < 0.01; T, 30%, p < 0.05), but much lower in group IVC1 and IVC2. The estradiol levels were significantly elevated only in group IVD (50%, p < 0.01) and group IVC2 (25%, NS). These results indicate that serum hormone levels are correlated with HIV infection group. The changes in steroid hormone concentrations during the development of HIV infection may have important implications for the immune response of patients The high cortisol and estrone levels of all groups, the elevated androgen levels in asymptomatic groups, and the low androgens in AIDS patients may form part of the complex network of immunomodulatory factors.

Ocular Toxoplasmosis in Human Immunodeficiency Virus-infected Patients

The files of 45 human immunodeficiency virus-infected patients with ocular toxoplasmosis were reviewed, with a median follow-up of eight months. The condition was unilateral in 37 of the 45 patients (82%) and was bilateral in eight (18%). Inflammation of the anterior chamber and the vitreous was present in 32 of 53 eyes (60%) and 38 of 53 eyes (72%), respectively. Cytomegalovirus retinitis developed during the follow-up period in nine patients (20%). Cerebral toxoplasmosis was concurrently diagnosed with the ocular toxoplasmosis in 13 patients (29%). The efficacy of the combination of pyrimethamine and sulfadiazine or clindamycin was assessed in 42 patients for the induction therapy and in 38 patients for the maintenance therapy. Induction therapy was always effective within a median period of six weeks. During maintenance treatment, the 24-month relapse rates were 0.20 and 0.18 for the 50-mg/day and 25-mg/day dosage of pyrimethamine, respectively. The overall 12-month survival rate was 0.72. Our results suggested that ocular toxoplasmosis has a better ocular prognosis than cytomegalovirus retinitis, but that it requires appropriate treatment because life-threatening cerebral involvement is often associated.

Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection

We report six cases of toxic megacolon in patients with human immunodeficiency virus (HIV). One case, at an early stage of HIV infection, mimicked a severe attack of Crohns disease, with a negative search for infectious agents. Subtotal colectomy was successfully performed with an uneventful postoperative course. The five other cases concerned patients with acquired immunodeficiency syndrome at a late stage of immunodeficiency. They were related to Clostridium difficile or cytomegalovirus (CMV) intestinal infection in two and three patients, respectively. One case of CMV colitis presented macroscopically and histologically as pseudomembranous colitis. Emergency subtotal colectomy, performed in the first four patients with acquired immunodeficiency syndrome was followed by a fatal postoperative outcome. The last patient treated conservatively by colonoscopic decompression, in association with anti-CMV therapy, had a favorable short-term outcome. From the experience of our series and data from the literature, we discuss the best diagnostic and therapeutic approach to toxic megacolon in patients with HIV.

Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection

Background: Patients with HIV infection frequently experience disease or treatment‐related myelosuppression leading to neutropenia. Neutropenia often leads to dose‐reduction or discontinuation of important myelosuppressive therapy. Objective: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. Design: Open‐label, non‐comparative, multicentre study in 200 HIV‐positive patients with neutropenia [absolute neutrophil count (ANC) < 1.0×109/l]. Filgrastim was started at 1 &mgr;g/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 &mgr;g on 1‐7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2‐5×109/l. Results: Filgrastim reversed neutropenia in 98% of patients (ANC ≥2×109/l), with a median time to reversal of 2 days (range 1‐16) and a median dose of 1 &mgr;g/kg/day (range 0.5‐10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of ≤ 300 &mgr;g/day (≤1 vial/day). Normal ANCs were then maintained with a median of 1 &mgr;g/kg/day (range 0.22‐10.6) during the treatment phase and 3×300 &mgr;g vials/week (range 1‐7) during the maintenance phase. Ganciclovir, zidovudine, co‐trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allowed > 80% of patients to increase or maintain dose‐levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV‐1 p24 antigen levels. Conclusion: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life‐threatening complications of neutropenia.

Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma

ObjectiveTo evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposis sarcoma. DesignA Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposis sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SettingHospital-based HIV units. PatientsThirty HIV-seropositive patients with mucocutaneous Kaposis sarcoma were enrolled and treated. InterventionsTreatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. ResultsOf the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15–202). For patients with a partial response, median time to treatment failure was 153 days (range, 15–558). Patients received a median of 10 cycles (range, 1–44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). ConclusionDaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposis sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and does not preclude the concurrent use of antiretroviral therapies.

Diversity of the V3 region of HIV in Paris, France.

Objective:To carry out, within France, a large-scale molecular epidemiological investigation on the principal neutralizing determinant of HIV-1, located in the third variable region (V3) of the envelope protein. Such investigations are of the utmost importance in the identification and monitoring of the distribution and spread of different viral strains internationally. Design:Using polymerase chain reaction (PCR), we examined the genetic variation of the V3 region sequences of 28 HIV-infected patients from Paris, France. Results:Comparison of the Parisian V3 loop sequences with other published data indicates that the range of diversity in France is included within that of a large group that contains sequences from North America, the rest of Europe, Japan, India and Africa. Variability appears to be lower in the V3 loop than in its flanking regions. Five out of the six putative N-linked glycosylation sites show preferential alterations to charged amino acids. We report two motifs at the tip of the loop that have not been described previously. Conclusions:The structural homogeneity and the wide geographic representation of the major V3 group suggests that a common strategy could be applied to a large proportion of isolates in the development of a broad-spectrum HIV vaccine.

Results of culture from colonoscopically obtained specimens for bacteria and fungi in HIV-infected patients with diarrhea

BACKGROUND The aim of our study was to determine the diagnostic yield of culture for bacteria and fungi from colonic biopsy specimens in 290 consecutive HIV-infected patients with diarrhea. METHODS During each colonoscopy, three biopsy specimens were homogenized and cultured on media for Salmonella and Shigella and for Campylobacter and Yersinia, on Loewenstein medium and on Sabouraud medium. RESULTS Cultures were found positive for one (n = 32) or two (n = 5) infectious agents in 37 cases, i.e., in 12.8% of the patients. Bacteria were isolated in 24 cases, and identified as Campylobacter jejunl-coli (n = 14), Salmonella (n = 2), Shigella (n = 1), or Pseudomonas aeruginosa (n = 7). Among the 14 patients with C. jejuni-coli intestinal infection, 11 had normal-appearing mucosa at colonoscopy, and 3 had a concomitant stool culture negative for Campylobacter. Mycobacterial cultures were positive for Mycobacterium avium intracellulare in 6 patients, who were already known as having a disseminated M. avium intracellulare infection from positive blood cultures. Fungal cultures were positive for Candida in 10 cases, without clear clinical significance. CONCLUSIONS The overall yield of culture for bacterial pathogens from colonic tissue in HIV-infected patients with diarrhea is low, but some individual cases of C. jejuni-coli infections may be detected from colonic tissue culture and not diagnosed by concomitant stool culture.

Lack of HPA-23 antiviral activity in HIV-infected patients without AIDS

A randomized study of 12 treated patients and seven controls was conducted in order to evaluate HPA-23 anti-HIV activity in HIV-infected patients. The antiviral activity was assessed by determining HIV p24 antigenemia. A persistence or even increase in antigenemia was shown in treated patients and thrombocytopenia was observed in nine out of the 12 patients. This suggests that HPA-23 should not be used in anti-HIV therapy.