acyclovir and AIDS-Related-Complex

Much controversy surrounds the use of antiretroviral drugs in HIV-infected patients. The many studies involving large numbers of patients that have been and are being conducted have raised as many questions as they have sought to answer. Given that no cure exists and that all clinically available drugs have only limited activity despite their high toxicity, the question of which drug (or combination of drugs) to use, and in whom, continues to vex both the clinician and the patient. Only three specific antiretroviral agents are currently licensed for use: zidovudine (ZDV), didanosine (dideoxyinosine, ddI) and zalcitabine (dideoxycytidine, ddC). This article reviews the major studies comparing the clinical efficacy of these drugs and the possible benefits of adding acyclovir to zidovudine therapy. The questions of when to begin antiretroviral therapy and the role of combination chemotherapy are discussed. Whenever possible, 'clinical' endpoints (death or clinical progression) are distinguished from 'softer' endpoints (surrogate markers of progression, such as the CD4 lymphocyte count) in the studies reviewed. Recommendations for the use of antiretroviral agents based on currently available published data are made.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Didanosine; Drug Therapy, Combination; Drug Tolerance; HIV Infections; HIV-1; Humans; Zalcitabine; Zidovudine

To evaluate the association between acyclovir use and survival in patients with advanced human immunodeficiency virus infection, observational data from 1044 persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3 following initiation of zidovudine were analyzed. Of these patients, 336 (32%) received regular acyclovir (> or = 6 weeks in 2 months). There were no differences in mortality data between acyclovir users and nonusers overall or when analyzed from 1 year after first use of zidovudine, from time of AIDS in those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use was associated with increased mortality (relative hazard, 1.28; P = .057) independent of herpesvirus infections and of other characteristics associated with mortality. In this study, the use of acyclovir at doses for treatment of herpes simplex virus infection in combination with zidovudine was not associated with prolonged survival.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Prospective Studies; Survival Rate; Zidovudine

To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC).. Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy.. Teaching hospital ambulatory clinics in eight European countries and Australia.. A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988.. Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts.. During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients.. These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Male; Safety; Zidovudine

To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS).. Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy.. Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia.. One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS).. Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay.. Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable.. Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; HIV Core Protein p24; Humans; Zidovudine

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

Topics: Acyclovir; Adult; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Male; Neoplasms; Opportunistic Infections; Safety; Zidovudine

Zidovudine delays the progression of human immunodeficiency virus (HIV) infection but is associated with hematologic toxicity at high doses. Regimens are needed that preserve or enhance efficacy and reduce toxicity. Acyclovir has been reported to potentiate the effect of zidovudine on HIV in vitro.. We conducted a Phase II open-label, dose-escalating trial to evaluate the clinical and antiviral effects of zidovudine at low (300 mg daily, 28 subjects), medium (600 mg, 24 subjects), and high (1500 mg, 15 subjects) doses, either with or without acyclovir (4.8 g) by random assignment. The subjects had the acquired immunodeficiency syndrome (AIDS)-related complex, but not AIDS. All of them had either HIV p24 antigenemia or plasma viremia and CD4-lymphocyte counts of 200 to 500 per cubic millimeter when they began treatment.. Performance scores and fatigue improved the most in the low- and medium-dose zidovudine groups (both P less than or equal to 0.025). Those assigned to low-dose zidovudine gained the most weight and had the greatest improvement in the mean CD4-lymphocyte count (from 321 per cubic millimeter at base line to 412 per cubic millimeter after 12 weeks, P = 0.01). The proportion of subjects in whom HIV antigenemia resolved, the decrease in the level of antigenemia, and the reduction in the plasma virus titers were similar at all three doses. Subjects assigned to receive the low or medium dose who subsequently crossed over to the 1500-mg dose (n = 19) did not have an increase in CD4-cell counts or a decline in levels of HIV antigen, but they did have dose-related toxicity. The addition of acyclovir to zidovudine was well tolerated, but it did not enhance any of zidovudine's antiretroviral effects.. In this pilot study a very low dose of zidovudine (300 mg) had clinical and virologic effects similar to those of higher daily doses (600 and 1500 mg). The minimal effective dose of zidovudine for the treatment of HIV infection has yet to be determined, and further studies of very low daily doses are warranted.

Topics: Acyclovir; Adult; AIDS-Related Complex; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Gene Products, gag; HIV Core Protein p24; Humans; Leukocyte Count; Male; Pilot Projects; Random Allocation; Viral Core Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Clinical Trials as Topic; Double-Blind Method; Humans; Multicenter Studies as Topic; Opportunistic Infections; Random Allocation; Zidovudine

A pilot study was initiated to explore a sequential combination antiretroviral regimen in 21 patients with AIDS or advanced human immunodeficiency virus (HIV) infection, who had received little or no prior anti-HIV therapy. The mean entry CD4 cell count was 184/mm3. Patients received 3-week cycles consisting of zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine for 1 week each. Overall, the regimen was well tolerated for up to 3 years. The principal toxicities were anemia, nausea, and vomiting; 1 patient developed retinal lesions. The mean CD4 cell count reached a peak of 64 cells/mm3 above baseline at week 8 (P = .005 compared to baseline) and remained above baseline for > 40 weeks. Patients also gained weight and had decreases in serum HIV p24 antigen. Eight patients developed opportunistic infections or tumors. Only 4 patients died during 3 years of follow-up. This regimen appears to be generally tolerable and to have anti-HIV activity. Additional studies will be needed, however, to learn how to best combine the available agents in patients with HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antigens, CD; Biomarkers; Body Weight; CD4 Antigens; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Core Protein p24; Humans; Male; Middle Aged; Pilot Projects; T-Lymphocyte Subsets; Time Factors; Zalcitabine; Zidovudine

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Bone Marrow; Brain Diseases; Dapsone; Ganciclovir; HIV Antigens; HIV Core Protein p24; Humans; Meningoencephalitis; Muscular Diseases; Neuropsychological Tests; Opportunistic Infections; Respiratory Function Tests; Retroviridae Proteins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Zidovudine

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antiviral Agents; Drug Interactions; Drug Therapy, Combination; Hematologic Diseases; Humans; Male; Middle Aged; Nervous System Diseases; Pilot Projects; T-Lymphocytes, Helper-Inducer; Thymidine; Zidovudine

Oral hairy leukoplakia was treated in six patients with (a) acyclovir (i.v. or p.o.), (b) 0.1% vitamin-A acid solution or (c) human beta-interferon-gel (10(5) I.E./g) in a total of 23 therapeutic courses. In 5/6 patients, acyclovir (7.5 mg/kg every 8 h i.v. or 5 x 400 mg p.o. over 5-10 days) led to partial (n = 1) or complete (n = 4) remission. After 1-6 months, however, the leukoplakia recurred in all cases. Vitamin-A acid solution (n = 3) led to remission in one and to improvement in the others. Human beta-interferon gel (n = 3) had no visible effect. The efficacy of acyclovir is further evidence of the concept that the Epstein-Barr virus is a major cause of oral hairy leukoplakia.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; AIDS-Related Complex; Drug Therapy, Combination; Humans; Infusions, Intravenous; Interferon Type I; Leukoplakia, Oral; Mouth Mucosa; Neoplasm Staging; Tretinoin

Patients who are homosexual, intravenous drug abusers, or have received multiple blood transfusions are at greater risk to contract the immunosuppressive disorders of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). These persons also have a greater chance of developing serious neurologic complications after an episode of Herpes zoster. We present two cases which emphasize the serious complications of Herpes zoster ophthalmicus in such patients. Since systemically administered acyclovir may shorten the disease course and reduce the complications of Herpes zoster in immunocompromised individuals, the authors favor treatment of all such patients who have Herpes zoster ophthalmicus with a seven-day course of high-dose (30 mg/kg/day) intravenous acyclovir. To minimize serious neurologic complications in such patients, treatment should be instituted immediately before the results of human immunodeficiency virus (HIV) testing are known.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Female; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Male; Middle Aged; Nervous System Diseases; Risk Factors

Seventeen patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis were treated with the antiviral drug ganciclovir (9-[1,3-dihydroxy-2-propoxy-methyl]-guanine, DHPG). Eight eyes of five patients developed rhegmatogenous retinal detachment after initiation of treatment. Multiple breaks in areas of peripheral, healed, atrophic retina accounted for the detachments. All seven eyes that underwent surgery had extensive retinal detachments that were reattached with vitrectomy and silicone oil. Retinotomy and retinal tacks were necessary in two cases that were complicated by severe proliferative vitreoretinopathy. In the fellow eye of one patient, laser treatment was used prophylactically to wall off a peripheral patch of healed retinitis. Endoretinal biopsies and culture were taken in five eyes; evidence of persistent cytomegalovirus was seen in two cases despite concurrent and clinically effective antiviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Follow-Up Studies; Ganciclovir; Homosexuality; Humans; Male; Middle Aged; Prospective Studies; Retina; Retinal Detachment; Retinal Perforations; Retinitis; Vitrectomy

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Age Factors; AIDS-Related Complex; Herpes Zoster; Homosexuality; Humans; Male; Risk Factors

The ocular findings in 38 patients infected by the Human T Cell Lymphotropic Virus Type III (HTLV III) are reviewed. Twenty patients were suffering from the Acquired Immunodeficiency Syndrome (AIDS) and 18 from the HTLV III related disease Persistent Generalised Lymphadenopathy (PGL). Cotton wool spots were found in the retinae of 8 patients at some stage of their disease and the prognostic significance of these is discussed. Cytomegalovirus (CMV) Retinitis was an ocular complication in eight of the patients with AIDS. The therapeutic effects of a new anti-viral drug, di-hydroxy propoxymethyl guanine (DHPG), are discussed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Antiviral Agents; Cytomegalovirus Infections; Eye Diseases; Fundus Oculi; Ganciclovir; Humans; Retinal Hemorrhage; Retinitis