GMHC Treatment Issues - Vol. 9, No. 12 - December 1995
Dennis Sawyer

Abbott Laboratories has announced details of the expanded access program for its protease inhibitor, ritonavir. Any person with HIV who is over twelve years old and has a CD4 cell count below 50 is eligible. The drug, in capsule or liquid form, will be provided by lottery to around 2,000 people worldwide (U.S. total: 1,200) in January, 1996. Participants in the lottery must register by December 30, 1995.

Doctors and people who want to enroll can call 800/414-AIDS or fax 800/336-2879 for additional information and the (relatively simple) application forms. You can e-mail Abbott Laboratories at ritonavir@pond.com. The program also has a site on the Internet's World Wide Web (http://www.pond.com/ritonavir).

Abbott is conducting a lottery because it says that the present available supply of ritonavir is highly limited. The company expects to file for FDA by the end of March, 1996, which could get ritonavir into pharmacies this summer.

In response to AIDS activists' suggestions, Abbott will be collecting survival data to compare the experience of those applicants who receive drug through the lottery with those who do not.

Note that Abbott has a long list of drugs incompatible with ritonavir due to ritonavir's impairment of liver metabolism. These drugs include the analgesics codeine, Demerol and Darvon; rifabutin; the antifungals ketoconazole and fluconazole; Roche's protease inhibitor Invirase (saquinavir); the anti-ulcer medication Tagamet; and various psychotropic agents such as Paxil, Xanax, Valium and Halcion.

Peptide T

Peptide T offers no benefit for people with HIV-related cognitive impairment, according to results from a National Institute of Mental Health (NIMH) sponsored study. The 215-person trial found no significant differences between the drug and placebo in overall neuropsychological function or in any of seven separately measured outcomes.

In response to these findings, Peptide Technologies of Australia, parent company to Peptech, has decided to discontinue all further studies of peptide T in the U.S., including the recently opened trial reported in September's Treatment Issues. Representatives of Peptech, the American subsidiary, claim to still believe in the drug. They are looking for alternative financing while independently analyzing the NIMH's data.

Pregnancy, HIV and Immune Status

A prospective British study of 145 women monitored immunologically during and after pregnancy revealed no evidence that pregnancy itself negatively affected their immunological markers. Although the women's CD4 lymphocyte counts fell during pregnancy, the CD4 and CD8 percent of total lymphocytes remained stable. The change in the CD4 count is related to a decline in the absolute lymphocyte count that occurs as a result of pregnancy and not to the redistribution of CD4 and CD8 cells observed in HIV disease progression. After pregnancy, CD4 counts rose, and the CD4 percentage was 2.5 points higher on average than would have been expected had there been no pregnancy.

Another prospective study of 416 Kenyan pregnant women who were matched and compared to a group of 407 HIV-negative controls also did not find any major differences in CD4 and CD8 counts during and after pregnancy. Both groups had lower CD4 percent but not CD4 counts after giving birth compared to prenatally.

Most studies of HIV-positive pregnant women have been done among asymptomatic populations. It is still unclear if pregnancy would have a deleterious effect on women with AIDS or symptomatic HIV disease. In addition, further studies are needed that evaluate the effect of pregnancy on viral load.

(RP Brettle. AIDS. Sept. 1995; 9(9):1177-84 and M Temmerman. AIDS. Sept. 1995; 9(9):1057-60.)

Treating CMV GI Disease

A randomized study of 48 patients with CMV gastrointestinal disease who received open-label ganciclovir or foscarnet found similar response rates to the two drugs. Patients were assessed using a visual analog score of symptoms, appearance of lesions on endoscopy and the presence of CMV inclusion bodies on repeat biopsy specimens after treatment. Eighty-three percent of those receiving foscarnet and 85 percent of those receiving ganciclovir showed a response by endoscopy and the CMV inclusion bodies disappeared in 73 percent of these.

Seventy-three percent of patients relapsed during follow-up. The time to progression was not significantly different among the two groups (sixteen vs. thirteen weeks).

Survival in both groups was less than 40 weeks and did not seem to be affected by continuing maintenance therapy. Patients were not randomized to maintenance or no maintenance. Only ten patients received maintenance therapy compared to 39 who did not. A much larger, randomized clinical trial is required to determine whether patients with CMV GI disease benefit from maintenance therapy. (C Blanshard et al. Journal of Infectious Diseases Sept 1995; 172(3):622-8).

Adenovirus Infections in HIV-Positive Patients

A prospective surveillance study of 63 HIV-positive patients and nine HIV-negative partners found evidence of adenovirus infection in 18 of the HIV-positive patients The analysis was done using restriction enzyme analysis. The most frequent site of infection was the gastrointestinal system in 17 of 18 patients with subgenus D, while urinary tract infection was caused by subgenus B or D. Diarrhea was present in 41 percent of those in whom adenovirus was found in the stool. Patients with low CD4 counts (under 150) had prolonged fecal excretion of adenovirus. How much adenovirus infection contributes to morbidity in AIDS patients is unclear, although one review of the literature showed that 45 percent of AIDS patients infected with adenovirus die within two months of virus detection. (SH Khoo. Journal of Infectious Diseases. Sept 1995; 172(3):629-37).

Steroids for PCP Do Not Increase OI Risk

A Spanish study compared the risk of TB in 72 patients with PCP who received steroids during their bout of pneumonia to the risk in 57 patients who did not. The mean total dose of steroid (methylprednisolone) was 420 mg and mean total days of use was twelve. The twelve and 24 months rates of both TB and atypical mycobacteria infections were similar for both groups. Rates of other AIDS-related conditions such as CMV and KS were also similar, although other authors have found higher rates of these infections after a short course of steroids in AIDS patients. (A Martos. AIDS. Sept 1995; 9(9):1037-41)

Chinese Herb Trial

St. Luke's-Roosevelt Hospital in New York has opened a phase I/II clinical trial of the combination of AZT and TJ-9, a preparation of a traditional oriental medicine known as Sho-Saiko-To (SSKT), or Xiao Chai Hu Tang. SSKT is a blend of seven medicinal herbs including bupleurum, scutelaria radix, pinellia, fresh ginger, ginseng, jujube and glycyrrhizin. It has been used for thousands of years to treat what the Chinese call lesser yang disorders, which include fevers, influenza, bronchitis, respiratory ailments, malaria, jaundice and hepatitis. SSKT appears to be fairly safe, although it has been reported to induce pneumonitis in a few elderly patients. In vitro data suggest that the blend may have anti-HIV activity by directly inhibiting reverse transcriptase, and by decreasing TNF-alpha and free radical promotion of viral replication.1,2 The data also suggest that the herbal formula is strongly synergistic with AZT.3 Additionally, SSKT may have some immune modulatory effects.

The St. Luke's-Roosevelt study will compare AZT plus SSKT (fifteen grams a day, divided into two packets drunk as a tea, three times a day) to AZT in 40 HIV-positive people with CD4 cell counts between 150 and 400, and a viral load greater than 20,000 RNA copies per ml. The study will last at least six months and will monitor patients for changes in viral load and other surrogate markers. For more information call Alison Spencer at 212/523-7238.

The doses chosen are those used traditionally in Chinese medicine. The study will not gather data on how well people's bodies absorb and distribute the herbal blend. This is unfortunate as there are no such data available, and therefore no way of knowing whether the concentrations found active in the laboratory can be achieved in human beings.

This lapse will make the study results harder to interpret. For example, if an antiviral effect is seen, would it be greater at higher doses? Also, SSKT is available from a number of sources, including the PWA Health Group in New York, and the cost of treatment can add up over time. It would be nice to know if SSKT does indeed reach its target cells.

1 Buimovici-Klein E. Antiviral Research. Oct-Nov 1990; 14(4-5):279-86.

2 Miyamoto K et al. Eighth International Conference on AIDS. Jul 19-24 1992; 2(abstract PoA 2345):A60.

3 Maitra U et al. Tenth International Conference on AIDS. Aug 7-12 1994; 1(abstract PB0491):265.

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