Gay Men's Health Crisis: Treatment Issues, Volume 8 no. 4 - June 1994
Gabriel Torres, M.D.

New Diagnostic Techniques for Cytomegalovirus Infections

Various studies presented new methods for diagnosing CMV infections, especially those of the central nervous system. In one Swedish study,[1] 148 patients with encephalopathy had their cerebrospinal fluid examined with PCR for detection of viral genome (DNA). Diagnoses of herpes simplex, varicella zoster, Epstein Barr virus, JC virus (which causes PML) and CMV were made using this PCR technique in 39 to 42 percent of patients. One presentation[2] showed how CMV encephalitis could be diagnosed by detection of CMV DNA by in-situ hybridization from cerebrospinal fluid and cells. Another technique used by an Italian group[3] utilized a CMV pp65 antigen test as a blood or cerebrospinal fluid marker of active CMV infection in HIV- positive patients with painful peripheral neuropathy. The development of these new diagnostic tests for CMV is crucial in making a prompt diagnosis of CMV encephalitis or neuropathy, which would otherwise require a brain or nerve biopsy.

Oral Ganciclovir To Prevent Cmv Retinitis Recurrence

A multicenter European-Australian study reported data comparing the use of oral and intravenous ganciclovir in preventing the recurrence of CMV retinitis.[4] Following induction with intravenous ganciclovir for two to three weeks, 159 patients were randomized to receive either oral ganciclovir (3 grams per day) or intravenous ganciclovir (5mg per kilogram of body weight once daily). Using photographic (fundoscopic) evaluation, the mean time to progression was 109 days for the intravenous group and 86 days for the oral group. These results are not too different from those of the trials in the United States and confirm that the oral drug is almost as effective in delaying disease progression as the intravenous drug. It is certainly less toxic.

Famciclovir for Herpes Zoster

A randomized placebo-controlled study found that famciclovir,[5] a new potent oral anti-herpes drug, was effective in the treatment of herpes zoster (shingles). Two doses of famciclovir (500 and 750mg) showed comparable efficacy and superiority over placebo in reducing the duration of virus recovery from zoster lesions as well as time to healing of lesions. A significant decrease in the duration of pain was detected for famciclovir-treated patients with severe rashes. The drug was well tolerated and had minimal side effects. A poster presentation reported that famciclovir also reduced the duration of post-herpetic neuralgia (pain which develops after the shingles have healed) from 128 days to 55 to 62 days.[6]

Toxoplasmosis Suppression

A randomized trial conducted by the ENTA Toxoplasmosis study group in France and Belgium[7] showed that the combination of pyrimethamine and clindamycin is clearly less effective for long term suppression of toxoplasmosis than the combination of sulfadiazine and pyrimethamine. Of 175 patients who had completed acute therapy for toxoplasmic encephalitis and who were randomized to one of the two suppressive regimens, 28 percent relapsed on the clindamycin group compared to 7 percent in the sulfadiazine group. A quarter of patients in each group had to discontinue therapy because of adverse effects, most commonly rashes in the sulfadiazine group and diarrhea in the clindamycin group. Other options for suppressive therapy of toxoplasmosis include atovaquone alone or in combination with pyrimethamine, azithromycin or rifabutin.

European Tuberculosis Studies

A multicenter European study[8] testing a three-drug against a four-drug regimen for the treatment of tuberculosis in HIV- infected patients was reported by a large consortium of researchers. The treatment regimen included isoniazid, rifampin, pyrazinamide with or without ethambutol. Of the 611 patients under study, 475 had TB confirmed by culture. The treatment failure rate was similar in both groups, as was overall mortality. The level of TB resistance to more than one drug was low (6 percent). In this population of TB patients with low levels of drug resistance, the addition of ethambutol did not seem to be justified.

A Spanish tuberculosis study[9] described an outbreak of hospital acquired, multidrug resistant tuberculosis (MDRTB) at a facility in Madrid. Twenty cases of MDRTB were diagnosed between December 1992 and October 1993. The majority (85 percent) of the patients died, 53 percent within the first month of diagnosis.

In a Rome hospital, 31 percent of the cases of TB were resistant to at least one drug.[10] Drug resistance was more common among patients with TB who had received previous anti- TB therapy and had been noncompliant.

A blood test measuring adenosine deaminase (ADA) is being studied in Spain[11] for rapid diagnosis of tuberculosis and may prove useful in cases where there is a need to make an immediate treatment decision. Other rapid TB tests include PCR, the tuberculostearic acid assay and the luciferase gene detection method.

Visceral Leishmaniasis

A relatively uncommon opportunistic infection in the United States was described by groups from three European countries (France, Spain and Italy). The disease, visceral leishmaniasis,[12] is caused by the Leishmania infantum protozoan which disseminates throughout the body and leads to high fever, liver and spleen enlargement and bone marrow disorders (leading to low red blood cell, neutrophil and platelet counts). The disease responds poorly to amphotericin, pentamidine or antimony drugs such as meglumine. Patients often relapse and the average survival is only 10.6 months. Resistance to meglumine was reported by one group of researchers in patients who had received several courses of the drug.[13] Immigrants from these European countries, as well as from Asia and South America who present with these symptoms should be evaluated for visceral leishmaniasis since it can be rapidly fatal if untreated.

Terbinafine for Nail Fungal Infections

Toe nail fungal infections are very common in HIV-positive persons and may be the first sign of an impaired immune system. A British group reported that five of fifteen HIV- positive patients with nail fungal infections caused by Tinea rubrum were successfully treated with a new antifungal drug called terbinafine.[14] Terbinafine is an allylamine antifungal agent that in the trial was given once daily at a dose of 250mg for twelve weeks. The five patients who were cured did not relapse after 48 weeks of follow-up. But terbinafine was not effective in the treatment of oral thrush in another study reported at the conference.[15]

Aspergillus Infections Associated with Hospital Renovation

A cluster of thirteen cases of an invasive fungal infection called aspergillosis was reported by a group of Italian investigators.[16] The cases were associated with exposure of patients to the fungal spores in a hospital ward undergoing reconstruction. The cluster confirms the dangers of hospital acquired infections for AIDS patients during construction or renovation, which may release fungi such as Aspergillus fumigatus into the air.

Vitamin B12 and Folate Supplements

A group from Spain studied 75 patients with CD4 cell counts under 500 who were randomized to receive AZT (500mg per day) alone or in combination with folate (15mg per day) and vitamin B12 (1,000 micrograms per month, injected intramuscularly).[17] The study attempted to determine whether the vitamin supplements prevented AZT-related suppression of blood cell production in the bone marrow. After one year of follow-up, there were no differences in the hemoglobin, hematocrit, white blood cell, neutrophil or platelet counts between the two groups. The researchers concluded that these vitamins were not effective in preventing AZT-related hematological effects. Other studies have reported a beneficial effect of vitamin B12 in HIV-related peripheral neuropathy.

Zinc and Opportunistic Infections

A poster presentation reported on the use of zinc sulfate supplementation as preventive of opportunistic infections.[18] Thirty volunteers received 200mg of the supplement a day in combination with AZT and were compared to a group of eleven patients who received AZT alone. The frequency of opportunistic infections in the next two years was reduced in the group who received the zinc supplementation (nine infections versus 26 in the control group). The opportunistic infections in which zinc may have played a role included PCP, toxoplasmosis, cryptococcus, salmonella and tuberculosis; no effects were seen for CMV and esophageal candidiasis.

Clotting Disorders in HIV-Positive Patients

A French group reported 35 episodes of unprovoked thromboses (clots) among twenty patients in three hospitals.[19] Nineteen of the clots were in the deep leg veins, fourteen in the pulmonary vessels and two in cerebral vessels, leading to strokes. A deficiency of free protein S had been noted in a previous study of HIV-positive patients, and was recorded in six of eight of the patients who developed clots and had levels of Protein S measured. Protein S is involved in preventing spontaneous formation of clots, and a deficiency predisposes to thrombotic (clotting) episodes. It is unclear why some HIV-positive persons have protein S deficiency and are consequently at higher risk of unprovoked thrombotic episodes.

References:

1. Cinque P, et al. abstract O20. Fourth European Conference on Clinical Aspects and Treatment of HIV Infecton, 1994.

2. Manicardi G, et al. abstract P138.

3. Volpi A, et al. abstract P137.

4. Knopse V, et al. abstract O21.

5. Tyring S, et al. abstract O24.

6. Tyring S, et al. abstract P159.

7. de Wit S, et al.; abstract P192.

8. European Tuberculosis Study Group. abstract O54.

9. Moreno V, et al. abstract 355.

10. Palmieri F, et al. abstract 356.

11. Fernández-González F, et al. abstract 360.

12. Rosenthal E, et al. abstract O27.

13. Gambarelli F, et al. abstract O28.

14. Nandwani R, et al. abstract P233.

15. Cartledge JD, et al. abstract O31.

16. Libanore M, et al. abstract P234.

17. Falguera M, et al. abstract P264.

18. Mocchegiani E, et al. abstract 306.

19. Pulik M, et al. abstract O62.

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