Summaries from the 5th Conference on Retroviruses and Opportunistic Infections: Part II
CONFERENCE COVERAGE
Note: The following summaries represent a selection of papers from those presented at the 5th Conference on Retroviruses and Opportunistic Infections held February 1-5, 1998, in Chicago, IL. It is important to recognize that many of these summaries are extracted only from the published abstracts, and it is possible that some of the material presented at the conference may have differed. The abstracts, as well as other information presented at the conference, are available on the Internet at www.retroconference.org.
Viral Load Assays
Three "ultrasensitive" assays for quantitation of plasma HIV RNA are currently available: Chiron Quantiplex 3.0 bDNA, with a sensitivity of 50 copies/mL; Nuclisens, with a sensitivity of 40-80 copies/mL; and the Roche Ultrasensitive Assay, with a sensitivity of 20-40 copies/mL. (Abstract S46.) In one study of 89 patients with less than 400 copies/mL by Chiron Quantiplex 2.0 bDNA assay, 38% had less than 40 copies/mL, and 26% had less than 20 copies/mL by the Roche Ultrasensitive Assay. (Abstract 529.)
Subjects with plasma HIV RNA "less than 1 copy/mL" have greater durability of response to antiretroviral therapy. In the investigator's parlance, less than 1 copy/mL means that the OD result on the quantitative assay is equal to background. Thus, the result is most likely below the usual lower limit of linearity of the assay, but whether it is truly "less than 1" cannot be determined by this method-hence, the quotation marks. Nonetheless, we will appropriately be seeing more use of this designation.
Complications of HIV Infection
Neurological Disease
Two hundred fifty patients with painful peripheral neuropathy were treated with placebo, amitriptyline, or acupuncture. There was no significant evidence of benefit from any of the regimens. (Abstract 462.) We have also demonstrated, in a case control study, the lack of efficacy of mexiletine. Large ACTG studies are also examining the efficacy of amitriptyline and mexilitene, as well as nerve growth factor in management of HIV-related painful peripheral neuropathy.
Several reports suggest that administration of protease inhibitor-based therapy is associated with prolongation of survival in patients with progressive multifocal leukoencephalopathy (PML). (Abstracts 463-465.) Two patients with PML had progression of their disease despite the administration of highly active antiretroviral therapy, interferon-alpha-2b and peptide T. (Abstract 466.) Three of seven patients with PML improved, and two stabilized while receiving cidofovir. (Abstract 467.) Unfortunately, this and other reports of benefit from cidofovir (see, e.g., Clin Inf Dis 1998;26:191-192), are difficult to interpret for two reasons: 1) PML has proven to not necessarily be inevitably progressive in AIDS patients, and 2) the institution of highly active antiretroviral therapy may also indirectly lead to control of PML.
One hundred twenty-nine patients who had completed 6-8 weeks of therapy for toxoplasmic encephalitis were randomized to maintenance therapy with either daily or thrice weekly sulfadiazine (1 g bid in both groups) plus pyrimethamine (25 mg daily or 50 mg thrice weekly). All patients received folinic acid. The cumulated estimated relapse rates in the two groups were 17% and 19% at one year and 30% and 19% at two years, respectively (P = 0.91), and there were also no differences in survival. Thus, thrice-weekly secondary prophylaxis appears to be as effective as daily prophylaxis for toxoplasmic encephalitis. (Abstract 468.)
The importance of management of elevated intracranial pressure in patients with cryptococcal meningitis is now widely recognized. Eight patients with cryptococcal meningitis and elevated intracranial pressure requiring serial LP or lumbar drainage for symptom control underwent constant infusion of normal saline into the lumbar cistern to evaluate outflow resistance (Neurology 1974;20:534). All patients had increased resistance indicative of impaired CSF absorption. Patients who developed symptoms of increased intracranial pressure at their equilibrium pressure or who do not reach equilibrium pressure are candidates for lumbar-peritoneal shunting. (Abstract 484.)
Wasting
Seventy-one patients with HIV-associated wasting were randomized to blindly receive either thalidomide or placebo. Thalidomide administration was associated with statistically significant weight gain; placebo recipients lost a mean of 0.4 lb. However, thalidomide administration was also associated with an increased incidence of somnolence, neutropenia, dizziness, asthenia, headache, and neuropathy, as well as with an increased plasma HIV RNA. (Abstract 476.)
Oxandrolone administration was associated with increased weight, body cell mass, and intracellular water content. (Abstract 477.)
Three patients, all male, receiving megestrol acetate for wasting developed avascular necrosis of the femoral head. (Abstract 478.)
Mycobacterial Infection
One thousand five hundred eighty-three patients with PPD skin test reactions more than 5 mm of induration were randomized to preventive therapy with either rifampin plus pyrazinamide for two months or isoniazid for 12 months. After a mean follow-up of 36 months, the rates of confirmed active tuberculosis were 0.8 and 1.1 per 100 patient-years (P = 0.33), respectively. Both regimens were well tolerated. (Abstract LB5.) Unfortunately, rifampin administration is contraindicated in patients receiving protease inhibitors.
Four patients with disseminated MAC who had received at least 12 months of macrolide-based therapy and whose CD4 counts were greater than 100 cells/mm3 and plasma HIV RNA greater than 10,000 copies/mL while receiving potent antiretroviral therapy had discontinuation of antimycobacterial therapy after having been demonstrated to have negative blood and bone marrow cultures. All patient's cultures remained negative during 1.5-7 months of follow-up. (Abstract 729.) Thus, there is hope for "cure" of MAC infection in some patients who respond to highly active antiretroviral therapy.
Cytomegalovirus Retinitis
It has been common practice to have patients with low CD4 counts undergo routine ophthalmological examinations in an attempt to detect asymptomatic CMV retinitis. However, in contrast to earlier reports, only two (0.8%) of 232 patients with CD4 count less than 100/mm3 screened by dilated fundoscopic examination were found to have asymptomatic CMV retinitis. (Abstract 756.)
Twenty-eight patients with CMV retinitis were randomized (2:1) to either immediate or deferred treatment with three weekly intravitreal injections of fomiversen, an antisense oligonucleotide that inhibits CMV replication. The median time to progression, as assessed with masked reading of fundus photographs, was 71 days in the immediate treatment group and 14 days in those assigned to deferred treatment (P = 0.0056). The most common side effects were transiently increased intraocular pressure and mild-to-moderate reversible intraocular inflammation. (Abstract LB6.)
Eight patients with CMV retinitis whose median CD4 count had reached 213 cells/mm3 as a consequence of the institution of highly active antiretroviral therapy had their anti-CMV maintenance therapy discontinued. No reactivation of retinitis was observed after a median duration of 156 days (range, 92-558 days). However, four patients developed manifestations of retinal inflammation not previously associated with CMV retinitis. Two had painless vitritis, and two had macular edema associated with vision loss occurring 2-16 weeks after a rise in CD4 cell counts in response to highly active antiretroviral therapy. (Abstract 757.) This newly described syndrome has been called "immune recovery vitritis" (Karavellas MP, Arch Ophthalmol 1998;116:169-175).
Cryptosporidiosis
Retrospective analysis of two trials of MAC prophylaxis with either clarithromycin or azithromycin found no evidence that the macrolides protect against the development of cryptosporidiosis. (Abstract 479.)
Recent studies have questioned the reported efficacy of paromomycin in the treatment of intestinal cryptosporidiosis. Eleven patients with diarrhea for 5-28 weeks due to cryptosporidiosis were given paromomycin 1 g bid and azithromycin 600 mg qd each for four weeks, followed by paromomycin alone for eight weeks. Only two received protease inhibitors; one was failing and the other first received it after stools were cleared of the protozoan. By week 12, there was a median decrease in oocyst excretion of more than 99%, and the number of stools had been reduced from 7.9 to 4.1 per day. (Abstract 481.)
As with other opportunistic infections, institution of highly active antiretroviral therapy is associated, in some cases, with resolution of cryptosporidiosis. (Abstract 480.)
Candida Infection
Three patients with advanced HIV disease and azole-resistant oropharyngeal candidiasis were treated with fluconazole 440 mg qd and GM-CSF 300 mcg subcutaneously daily for 14 days. Despite MICs to fluconazole greater than 80 ug/mL and failure of prior therapy with 800 mg fluconazole daily, all three patients had "complete resolution of their disease." (Abstract 491.)
Viral Hepatitis
Acute hepatitis A virus infection was diagnosed in seven HIV-infected patients with CD4 counts ranging from 125 to 810/mm3. Six were ill for from one to four weeks and had peak ALT of 1017 to 7000 IU/mL. The seventh, who had received immune serum globulin after a known hepatitis A exposure, had a mild, one-week illness with peak SGPT of 110 IU/mL. Three patients who maintained their stable antiretroviral therapy during the illness had stable plasma HIV RNA levels. The clinical and laboratory course of acute hepatitis A virus infection in these seven HIV-infected patients could not be distinguished from that in non-HIV-infected patients. (Abstract 498.)
HIV-infected patients often respond ineffectively to vaccines, including to the three doses of hepatitis B that constitute primary vaccination against this virus. Only 10 (50%) of 20 HIV-infected patients without antibody to hepatitis B virus or prior vaccination against it and with CD4 greater than 200/mm3 on stable antiretroviral therapy who received three doses of hepatitis B vaccine (20 mcg of Genhevac per dose) developed protective levels (> 10 IU/mL) of antibody to hepatitis B virus. Six doses of vaccine led to seroconversion in 88% of recipients. There was a transient increase in plasma HIV RNA. (Abstract 497.) Unfortunately, this study has too few subjects to provide the conclusion that six doses of hepatitis B vaccine are better than three. This will require further study.
3TC is under investigation for the treatment of chronic hepatitis B virus infection, an infection commonly encountered in patients who are also HIV infected. One hundred twenty-two patients in the CAESAR trial of antiretroviral therapy were HBsAg positive at the time of randomization to one of three regimens-two of which contained 3TC. HBV DNA decreased by a median of 2.0 log10 in the 3TC groups, while there was no change in the third group, which did not receive this nucleoside analog. There was loss of HBeAg in seven (22%) of 32 in the former group and in none of seven in the latter. (Abstract 496.)
Molluscum Contagiosum
Three patients with extensive molluscum contagiosum, despite highly active antiretroviral therapy, had complete resolution of their cutaneous disease after treatment with cidofovir. Two were given the drug intravenously and one topically as 3% cidofovir in Dermovan. (Abstract 504.)
If these observations prove true, they provide us with the first potential non-ablative therapy of this superficial pox virus infection.
Thrombotic Thrombocytopenic Purpura?
The components of a thrombotic thrombocytopenia-hemolytic uremic syndrome-like (schistocytosis, anemia, and thrombocytopenia occurred together with neurologic dysfunction, fever, or renal insufficiency)-were seen in 7% of 350 consecutive HIV patients admitted to hospital. (Abstract 503.) But is this really TTP?
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