TreatmentUpdate57, Vol. 7, No. 3 - March 1995 ************************************************* published by Community AIDS Treatment Information Exchange, Suite 420 - 517 College St., Toronto, Ontario, Canada M6G 4A2 ************************************************* INFECTION FIGHTERS A. Mepron or iv pentamidine for PCP * BACKGROUND The life-threatening infection PCP is one of the more common infections seen in patients in North America and Western Europe. Symptoms can include fever, shortness of breath and dry cough. Standard therapy is Bactrim(R)/Septra(R) or iv (intravenous) pentamidine. Alternatives may include clindamycin-primaquine, dapsone-trimethoprim, trimetrexate-dapsone and Mepron(R) (atovaquone, Wellvone(R)). There are problems associated with every therapy as some patients cannot tolerate sulfa drugs. Mepron is a relatively new treatment for PCP, and the manufacturer, Glaxo-Wellcome, has been conducting trials comparing it to standard therapy. * STUDY DETAILS In one experiment, researchers tested Mepron against iv pentamidine. Although 144 subjects (139 men and 5 women) entered the trial the company used data on 56 subjects who received Mepron and 53 who received pentamidine. Only subjects with mild-to-moderate documented PCP entered the study. Researchers assigned subjects at random to one of 2 arms of the study; either 750 mg Mepron "3 times daily with food" or one daily dose of pentamidine of either 3 or 4 mg/kg of body weight. Subjects were supposed to receive either drug for 3 weeks. Those subjects with "moderately severe PCP also received oral [corticosteroids]" to reduce inflammation. Subjects and doctors knew which drugs subjects received. * RESULTS According to the printed analysis, - 57% of subjects who received Mepron and 40% of who received iv pentamidine "were successfully treated." This difference was not statistically significant. - More subjects receiving Mepron (29%) were likely not to improve than subjects receiving pentamidine (17%). This difference was not statistically significant. - Subjects given pentamidine were more likely to stop recovering because of drug toxicity than subjects given Mepron. * SIDE EFFECTS Among subjects who received pentamidine, serious side effects included low blood sugar, nausea and vomiting. Among subjects receiving Mepron the most serious side effect was "rash". Subjects receiving Mepron reported "increased cough." * CONTESTED CONCLUSIONS The study doctors concluded that "oral [Mepron compared to iv pentamidine] have similar rates for successful treatment of mild to moderate PCP..." Doctors not associated with this study warn that "[subjects] in this study had a treatment failure rate that was 71% higher if they received Mepron than if they received iv pentamidine." Other doctors noted that within the first 4 weeks of treatment more subjects assigned to Mepron (13%) died than subjects assigned to pentamidine (8%). This difference was not statistically significant. By the 8th week the rates of death were similar. Although Mepron is less effective than standard treatment (Bactrim/Septra or iv pentamidine) it remains an option, particularly for patients who cannot tolerate sulfa drugs. REFERENCES: 1. Dohn MN, Weinberg WG, Torres RA, et al. Oral atovaquone compared to iv pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Annals of Internal Medicine 1994;121(3):174-180. 2. Lederman MM, and Van der Host C; Stoeckle M and Tannenberg A. Atovaquone for Pneumocystis carinii pneumonia. Annals of Internal Medicine 1995;122(4):314-315. 3. Hughes WT. The role of atovaquone tablets in treating pneumocystis carinii pneumonia. Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology 1995;8(3):247-252. II TESTING A. Pregnancy and the immune system * BACKGROUND Researchers studying pregnancy have found a relationship between the mother's immune system and the placenta (the 'organ' that develops around the fetus). The placenta is rich in blood vessels from the mother and fetus so that the fetus can received oxygen and nutrients from the mother. In order for the fetus to survive, it must be protected from the mother's immune system. It appears that the placenta produces chemicals that alter the mother's immune system. * CYTOKINES FOR SURVIVAL Research on pregnant mice and humans suggests that the immune system of the female parent undergoes a complicated change during pregnancy. One arm of the immune system called CMI (cell-mediated immunity) seems to become weaker during pregnancy. The body needs CMI to fight off certain microbes that tend to 'hide' inside cells. Examples of these microbes include CMV and SV, the bacteria that cause TB and related infections and, the parasite that causes the brain infection 'toxo' (toxoplasmosis). To help fight off these microbes the immune system releases chemicals such as IL-2 and interferon-gamma. Interestingly, large doses of these two chemicals can kill the fetus. The other arm of the immune system is called humoral immunity. Chemicals that strengthen this response include IL-4, -6 and -10. Antibody-producing B cells are an important part of this arm. In experiments on pregnant mice who are not likely to carry the fetus for the full length of pregnancy, injections of IL-3 and GM-CSF (granulocyte macrophage-colony stimulating factor) help correct this problem. Researchers in Alberta and India found that the placentas from women prone to abortion tend to release IL-2, interferon-gamma and TNF (tumour necrosis factor). * HELPING THE MOTHER It appears that pregnancy seems to strengthen humoral immunity and weaken CMI. This change seems to help the fetus survive pregnancy. Another issue is the survival of the mother. To strengthen humoral immunity may mean that pregnant women may not be able to maintain a strong defence (CMI) against HIV and other microbes. Thus pregnancy may further weaken the immune systems of HIV-infected women. Researchers need to find out more about the immune systems of women in general and women with HIV/AIDS in particular. REFERENCES: 1. Wegmann TG, Lin H, Guilbert and Mossman TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunology Today 1993;14(7):353-356. 2. Clarke AG and Kendall MD. The thymus in pregnancy: the interplay of neural, endocrine and immune influences. Immunology Today 1994;15(11):545-551. 3. Moncayo HE, Solder E, Abfalter E and Moncayo R. Cytokines and the maternal-fetal interface. Immunology Today 1994;15(6):295. B. Pregnancy and HIV: why some babies escape infection * THEORY VERSUS REALITY According to the World Health Organization, approximately 1 million children worldwide are infected with HIV. In the USA every year 7,000 HIV-infected women give birth to between 1,000 and 2,000 infected infants. On average between 75% to 85% of babies are born without HIV infection although their mothers are infected. Several research teams are studying infants born to these mothers, but these teams have produced more theories than clear answers. In general, it seems that the state of the mother's immune system and severity of HIV infection may play a role in the outcome of pregnancy. In some studies it appears that breast feeding may transmit the virus. In several studies it appears that fetuses' with strong CMI (cell-mediated immunity) were less likely to be HIV-infected compared to other fetuses with weak CMI. Women with HIV-2 infection seem less likely to transmit that virus to the fetus. REFERENCES: 1. Glausiuz J. HIV: The babies who escape. New Scientist 16 April, 1994, pages 38 to 42. 2. Khouri YF, McIntosh K, Cavacini L, et al. Vertical transmission of HIV-1: correlation with maternal viral load and plasma levels of CD4 binding site anti-gp120 antibodies. Journal of Clinical Investigation 1995;95:732-737. 3. Clerici M, Sison A, Berzofsky JA, et al. Cellular immune factors associated with mother-to-infant transmission of HIV. AIDS 1993;7:1427-1433. 4. Kilk SC, Wara DW, Landers DV and Levy JA. Features of HIV-1 that could influence maternal-child transmission. Journal of the American Medical Association 1994;272(6):467-474. 5. Douglas SD. Immunological and virological clues for mother-to-child transmission of HIV-1 and HIV-2. Journal of the American Medical Association 1994;272(6):487-488. 6. Rowlands-Jones SL, Nixon DF, Alderhous MC, et al. HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. Lancet 1993;341:860-861. C. Pregnancy and HIV: a French study * A 7-YEAR STUDY IN FRANCE In this project, researchers have been keeping track of babies born to HIV-infected mothers. The mothers were asked not to breast feed their infants. Here is the subject profile: - average age was about 27 years - about 1/4 were from Central Africa - about 5 % were from the West Indies - 80% had either no symptoms or just persistently swollen lymph nodes - average CD4+ cell count was roughly 600 cells - average % of lymphocytes that were CD4+ was 30% - average CD8+ cell count was 864 cells - average % of lymphocytes that were CD8+ was 44% No women used anti-HIV drugs during the study. * TRANSMISSION RATE OF 20% The researchers reported data on 848 mothers (and their children). They found that about 20% of babies had HIV infection. The transmission rate has remained roughly the same since 1986. Researchers analysed other data to find out what factors might affect the infection of babies. They found that the following factors did not have any relation to the infant being HIV-infected: - being born in Central Africa - cutting open the mother's womb to release the infant - whether the mother was infected through needles or sex The following factors appeared to be associated with infection of the fetus: - breast-feeding - age-older mothers - low CD4+ cell counts (explained below) - detectable p24 antigen - symptoms of HIV infection On average, women who had a CD4+ cell count of 601 cells or more had a 15% chance of giving birth to an infected infant. Women who had less than 200 CD4+ cells had a 43% chance of giving birth to an infected infant. These differences were statistically significant; that is, not likely due to chance alone. Women with the lowest risk of transmission (12%) had more than 500 CD4+ cells and less than 40% of CD8+ cells. Women with the highest risk (50%) of transmission had less than 200 CD4+ cells and more than 40% CD8+ cells. The length of time infants were breast fed did not seem to affect which infants would become HIV-infected. Mothers who were more than 35 years old had a transmission rate of 30% and those under the age of 25 had a rate of less than 16%. Subjects with no symptoms of HIV infection had an 18% risk of transmission while those with AIDS had a rate of 35%. REFERENCES: 1. Mayaux M-J, Blanche S, Rouzioux C, et al. Maternal factors associated with perinatal HIV-1 transmission: the French cohort study-7 years of follow-up observation. Journal of Acquired Immunodeficiency Syndromes and Human Retro- virology 1995;8(2):188-194. D. Pregnancy and HIV-studies from Tanzania and Cote d'Ivoire * STUDY DETAILS Researchers in Sweden and Tanzania conducted a 3 year study to try and find out factors that might explain why some babies are born without HIV infection. The researchers tested blood from 3,000 mothers and found that roughly 12% were HIV infected. Data analysis relied on information from 255 mothers,138 of whom were infected with HIV, and 117 who were not. The researchers noted CD4+ and CD8+ cells, the HIV protein p24 and beta2-microglobulin (á2-m). Blood levels of á2-m increase as the immune system weakens in subjects with HIV infection. * RESULTS On average about 22% of infants born to infected mothers were also infected. The researchers found that the following factors were linked to infection in the infants: - higher-than-normal blood levels of á2-m - detectable p24 antigen - low blood levels of CD4+ cells * á2-M On average, infants born to women with relatively high blood levels of á2-m (2 mg/litre or greater) had a 34% chance of also being HIV-infected. In women with less than 2 mg/L of á2-m, the chance of giving birth to an infected infant was 14%. * %CD4+ CELLS The researchers did not find any statistically significant relations between infected infants and CD4+ cell counts. When they measured the percent of lymphocytes that were CD4+, then low %CD4+ levels were linked to infants being infected. For mothers with %CD4+ cells 20% or less, the chance of an infant being born with HIV infection was about 33%. Mothers who had more than 20% CD4+ cells had a transmission rate of 14%. Among mothers with less than 20% CD4+ cells and blood levels of á2-m greater than 2 mg/L, the rate of transmission was 54%. Although p24 antigen was more commonly detected in blood samples from mothers who transmitted the infection (than in those that didn't), "few mothers had [detectable p24]". * COTE D'IVOIRE Another study in C8te d'Ivoire analyzing data from over 600 poor HIV-1 infected women, found that pregnant women had a 25% chance of giving birth to an infected infant. For women with HIV-2, the equivalent figure was 1%. REFERENCES: 1. Bredberg-Raden U, Urassa W, Urassa E, et al. Predictive markers for mother-to-child transmission of HIV-1 in Dar es Salaam, Tanzania. Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology 1995;8(2):182-187. 2. Adjorlolo-Johnson G, De Cock D, Dkpini E, et al. Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Cote d'Ivoire. Journal of the American Medical Association 1 994;272(6):462-466. E. French-American study on AZT for pregnant HIV-infected women * STUDY DETAILS We now report results from the study ANRS 024/ ACTG 076. Researchers randomly assigned subjects to one of 2 arms in the study; either AZT or placebo. Those assigned to AZT received 500 mg/day orally before giving birth and during birth they received iv AZT 2mg/kg of body weight for 1 hour, "followed by 1 mg/kg/hour until birth." After birth the infant received AZT 2 mg/kg every 6 hours for 6 weeks. Subjects and their infants received regular monitoring. For their analysis, researchers used data from 205 women assigned to receive AZT and 204 women assigned to placebo. Neither doctors nor subjects were supposed to know who received AZT and who did not. At least 1/2 of the subjects: - were 25 years old - had 550 CD4+ cells - were pregnant for 6 months before entering the study - received AZT for 11 weeks before giving birth * EFFECT(S) OF AZT Researchers made decisions about the effect of AZT or placebo in a number of ways. In one calculation, 180 mothers and their infants received AZT while 183 others did not. Roughly 8% of infants born to mothers in the AZT arm were infected as were 26% of those born to mothers in the placebo arm. Since 8% of infants born to mothers who used AZT were also HIV-infected, treatment with AZT does not provide 100% protection. * TOXICITY--THE MOTHERS Roughly the same proportion of women reported side effects in each arm of the study. There were no deaths among the mothers in either arm during the study. Six months after birth, 95% of women in both arms of the study had CD4+ cell counts "greater than 300 CD4+ cells". * TOXICITY--THE INFANTS Five deaths occurred in subjects receiving AZT and 3 others in those assigned to placebo. None of these deaths appeared to be caused by AZT or placebo. Doctors detected a variety of physical defects in 33 infants but these were evenly divided between the 2 arms of the trial. Nearly twice as many infants given AZT had reduced blood levels of haemoglobin (needed for moving oxygen) than others not given the drug. Six weeks after birth (when they stopped using AZT) haemoglobin rose. References appear in section F below. F. AZT and pregnancy-unanswered questions and difficult decisions * WHAT NEXT? Despite the apparent benefit of AZT in ANRS 024/ACTG 076 (details of which appear above) many questions remain unanswered . * TIMING OF 'TREATMENT' It appears that HIV infection of the fetus happens late in the course of pregnancy; before, during and possibly after birth (via breast milk). In making an attempt to protect the fetus, researchers gave women oral and iv AZT, and later their infants received the drug as well. One issue arising from this research is the timing of treatment. Can shorter exposure to AZT late in pregnancy also provide the same or better protection from HIV? * AZT: DELIVERY AND DOSE Women in this trial received oral AZT at a dose of 500 mg/day. Can the fetus of pregnant women benefit from a reduced dose of AZT-300 mg/day? The women in the trial also received iv AZT, is this always needed? AZT is supposed to work by interfering with the viral enzyme RT (reverse transcriptase); it works only once a cell has already been infected by HIV. In experiments on health care workers and patients accidentally infected with HIV, treatment with AZT by itself or the related drug ddI and interferon-alpha has not protected people from HIV infection. As well, it is not clear what might happen to the fetus if the mother develops virus that is resistant to AZT. * OTHER PREGNANT WOMEN Readers cannot assume that the results from this study mean that fetuses of other pregnant HIV-infected women will 'benefit' from AZT treatment of their mother. The subjects in this trial were a "select group of women", having - few, if any, symptoms of HIV infection - little past use of AZT - relatively high CD4+ cell counts Based on results from ANRS 24/ACTG 076, it is not clear what might happen to the fetuses of other pregnant HIV-infected women who have lower CD4+ cell counts, used AZT for long periods of time and/or have serious symptoms. * TOXIC FOR SOME BUT NOT OTHERS? Results from the French-American study suggest that toxicity from AZT to infants is minor, but it is not clear what will happen to mothers and infants over the long term. Mothers may be understandably wary given the interim results from the American study ACTG 152. In that trial hundreds of infants-most aged between 3 and 30 months-received AZT or ddI or a combination of both drugs. An independent safety monitoring board recommended that the trial be stopped because babies receiving AZT alone, compared to the other 2 groups, had: - stopped growing - more life-threatening infections - brain damage - higher rates of death Given that 75% to 85% of pregnant HIV-infected women give birth to healthy, non-HIV-infected babies, there are concerns about giving all such women (and their fetuses) AZT. Perhaps research using less toxic drugs such as nevirapine might be useful. * HOW DOES AZT WORK? Doctors associated with this study do not know why AZT treatment apparently reduced the chance of HIV infection of the fetus. Experiments on baby monkeys infected with SIV suggests that AZT may delay the appearance of AIDS. Researchers think that the anti-viral effects of AZT may be the source of its benefit--but this has not been formally proven. Indeed, researchers do not have a precise and clear understanding of exactly why most babies born to HIV-infected mothers do not have HIV infection. REFERENCES: 1. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-fetal transmission of Human Immunodeficiency Virus type 1 with Zidovudine treatment. New England Journal of Medicine 1994;331(18):1173-1180. 2. Rogers MF and Jaffe HW. Reducing the risk of maternal-infant transmission of HIV: a door is opened. [Editorial] New England Journal of Medicine 1994;331(18):1222-1223. 3. Palmer DL, Njelle BL, Wiley CA, et al. HIV-1 infection despite immediate combination antiviral therapy after infusion of contaminated white blood cells. American Journal of Medicine 1994;97:289-295. 4. Glick ME. Interim results lead to discontinuation of AZT-only study arm. Press release. February, 1995. 5. Bayer R. Ethical challenges posed by Zidovudine treatment to reduce vertical transmission of HIV. New England Journal of Medicine 1994;331(18):1223-1225. 6. Van Rompay KKA, Otsyula MG, Marthas ML, et al. Immediate Zidovudine treatment protects Simian Immunodeficiency Virus-infected new born macaques against rapid onset of AIDS. Antimicrobial Agents and Chemotherapy 1995;39(1):125-131. 7. Dabis F, Mandelbrot L, Msellati P and van de Perre P. Zidovudine to decrease mother-to-child transmission of HIV- 1: is it a good thing for developing countries? AIDS 1995;9(2):204-206. 8. Michie CA and Hyer W. When does HIV cross the placenta? Lancet 1995; 345(8948): 517-518. 9. Kesson AM, Fear WR, Williams L, et al. HIV infection of placental macrophages: their potential role in vertical transmission. Journal of Leukocyte Biology 1994;56:241-246. 10. Bryson YJ, Pangs, Wei LS, et al. Clearance of HIV infection in a perinatally infected infant. New England Journal of Medicine 1995;332(13):833-838. 11. Schwartz DH, Sharma UK, Perlman EJ and Blakemore K. Adherence of Human Immunodeficiency Virus lymphocytes to fetal placental cells: a model of maternal->fetal transmission. Proceedings of the National Academy of Sciences USA 1995; 92:978-982 III VACCINES A. Vaccines for HIV * BACKGROUND During the past 10 years researchers have been constructing a number of potential anti-HIV vaccines. Most of these vaccines were designed to stimulate one arm of the immune system (humoral immunity) and cause the body to make anti-HIV antibodies. The theory supporting this design relied on a number of now outdated ideas, one of which was that anti-HIV antibodies would protect people from HIV infection. Unfortunately most people with HIV/AIDS make these antibodies which do not appear to protect them from infection or further damage to the immune system. It appears that the other arm of the immune system--CMI (cell-mediated immunity)-- weakens over time. Many of the life-threatening infections seen in AIDS occur because CMI has declined. Researchers in France, Montr‚al and California studying monkeys with AIDS have reached the same conclusion. They are trying to design vaccines that can boost CMI against SIV (the virus that causes AIDS in some monkeys) and HIV. These vaccines may also be used to help the immune systems of people with HIV/AIDS. * HELPING VACCINES WORK Usually vaccines have 2 parts. The first part (called the adjuvant) is designed to enhance the immune response to the vaccine (the second part). Adjuvants generally used in vaccines include: - alum (aluminum hydroxide) - CFA (complete Freunds adjuvant made with light mineral oil) - extracts of bacteria such as MDP (muramyl dipeptide) Most adjuvants stimulate production of antibodies and favour humoral immunity. Scientists working on developing HIV/AIDS vaccines are trying to find adjuvant that can help T cells respond to a vaccine. Researchers experimenting on humans with cancer are testing a number of chemicals designed to boost CMI. Reviewing their early results, it is not clear which chemicals are best for boosting CMI. Here are several chemicals that are being tested for their ability to boost T cells so that they will be stimulated by vaccines: - interleukins 2 and 12 - DTC (Immuthiol(R) ) - MIMP (methyl inosine monophosphate) - thymic hormones such as thymosin alpha 1, thymopentin, thymic humoral factor - levamisole (Ergamisol(R) - indomethacin (Indocid(R) - complete Freunds adjuvant (CFA) REFERENCES: 1. Hadden JW. T-cell adjuvants. International Journal of Immunopharmacology 1994; 16(9):703-70. 2. Vaslin B, Le Grand R, Vogt G, et al, Induction of Humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection? Vaccine 1994;12(12):1132-1140. 3. Chan WL, Rodgers A, Grief C, et al. Immunization with class 1 human histocompatibility leukocyte antigen can protect macques against challenge infection with SIVMAC-32H AIDS 1995;9(3):223-228. B. The Salk HIV vaccine-results from several studies * BACKGROUND Learning that CMI (cell-mediated-immunity) was reduced in patients with AIDS a research team led by Dr. J. Salk (creator of the polio vaccine) designed a potential anti-HIV vaccine called the immunogen. To make this vaccine, technicians attacked HIV with chemicals and radiation so that it could not cause any infection. They then removed the HIV-protein gp120. This protein can impair the ability of the immune system to fight HIV. To boost the response of the immune system to the vaccine, researchers used an adjuvant called IFA (incomplete Freunds adjuvant) using light mineral oil and other ingredients. IFA appears to stimulate both CMI and humoral immunity. The researchers also used a small amount of another HIV protein called p24 with the adjuvant. * STUDY DETAILS All subjects in this study were adults, had CD4+ cell counts of at least 600 cells, and had no symptoms of HIV infection. As well, subjects did not have B-cells producing high levels of unnecessary antibodies. Researchers randomly assigned subjects to receive 3 injections of the vaccine or just the adjuvant over six months. * MEASURING T CELLS Different labs have different procedures for reporting a person's CD4+ cell count. Sometimes the actual number of CD4+ cells is computed. Sometimes it is not. CD4+ cells are lymphocytes, and lymphocytes are white blood cells. The white blood cells are expressed as an estimate of the actual number of white blood cells in 1 cc of blood. CD4+ cells are usually expressed as percentages. For example, usually lymphocytes make up between 25% and 50% of all white blood cells. Normally, CD4+ cells make up 30% to 45% of all lymphocytes. This is an actual measurement. To find out the CD4+ cell count some small calculations are needed. Thus CD4+ cell counts are calculated while the %CD4+ are actual measurements. Thus %CD4+ and %CD8+ are more accurate than the calculated number of cells. In a future issue of TreatmentUpdate we will provide details on how to find out the number of CD4+ and CD8+ cells * RESULTS--CD4+ CELLS At the time subjects entered the study their average %CD4+ (the proportion of lymphocytes that were CD4+ cells) was roughly 31%. Subjects who received the immunogen had a slower rate of loss of CD4+ cells compared to subjects who received IFA. This difference between the two groups was statistically significant that is, not likely due to chance alone. * RESULTS--ANTIBODIES Both groups of subjects produced increased amounts of antibodies against the HIV protein p24. Subjects who received the immunogen made more antibodies. This difference was also statistically significant. * RESULTS--CMI, VIRUS AND TOXICITY To measure CMI technicians inject a small amount of protein from yeast or bacteria under the skin. In people with good CMI there is usually a reaction within 48 hours-swelling and redness at the injection site. The greater the reaction the higher the level of CMI. Among the subjects given the immunogen, CMI apparently increased by 21% while subjects in the IFA group had their CMI fall by 28%. It appeared that subjects who received the vaccine had a slower increase in production of HIV compared to who subjects received IFA. Again this difference was also statistically significant. Although some subjects used AZT while in the study, it did not appear to reduce production of H[V during the study. Researchers reported no serious side effects in people in both groups. REFERENCES: 1. Trauger RJ, Ferre F, Daigle AE, et al. Effect of immunization with inactivated gp120-depleted Human Immunodeficiency Virus type 1 (HIV-1) immunogen on HIV-1 immunity, viral DNA and percent of CD4+ cells. Journal of Infectious Diseases 1994;169:1256-1264. 2. Moss RB, Ferre F, Trauger R, et al. Inactivated HIV-1 immunogen: impact on markers of disease progression. Journal of Acquired Immunodeficiency Syndromes 1994;7 (Supplement l):s21-s27. 3. Smith GW. Calculating your absolute T4+ count. IN: Testing AIDS 1989; page 4. C. Salk HIV vaccine--immune boosting effects * STUDY DETAILS In this study researchers focused on the effect of the immunogen on CMI. Subjects in this were symptom-free, had at least a minimal level of CMI and at least 600 CD4+ cells. Researchers enrolled 46 men and 2 women, and divided them up at random and placed subjects into 5 groups, each receiving a different dose (50, 100, 200 or 400 mcg (micrograms) of the vaccine or just IFA. Subjects received at least 1 injection of the vaccine or IFA. Technicians then tested subjects regularly for CMI. If the results of the tests suggested that CMI was weak then the subject received a booster shot of the vaccine (to a maximum of 6 boosters). Researchers monitored subjects for up to 2 years. They have just released data on the results of the first 9 months. * RESULTS At the beginning of the study subjects had various levels of CMI. Over time, subjects who received the vaccine had higher and sustained levels of CMI against H1V compared to subjects who received IFA. For each dose of the vaccine this effect was statistically significant. It appeared that the 100 mcg dose was "as effective as the 400 mcg dose in [boosting CMI against HIV] over the course of the study." Based on these preliminary and promising results, the Immune Response Corporation is planning larger studies. REFERENCES: 1. Turner JL, Trauger RJ, Daigle AE and Carlo DJ. HIV-1 Immunogen induction of HIV-1-specific delayed-type hypersensitivity: results of a double-blind, adjuvant- controlled, dose-ranging trial. AIDS 1994;8(10):1429-1435. Copyright (c) 1995 - CATIE. Distributed by AEGIS, your online gateway to a world of people, knowledge, and resources. 714.248.2836 * 8N1/Full Duplex * v.34+