The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

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.     

Acetaminophen does not impair clearance of zidovudine

OBJECTIVE: To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity. DESIGN: Dose escalation, drug interaction study. SETTING: University clinical research center. PATIENTS: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. INTERVENTIONS: Acetaminophen and 200 mg of zidovudine simultaneously every 4 hours. For 13 patients, the unit dosage of acetaminophen was 325 mg for 3 days; for 8 patients, the dosage was 650 mg for 3 days; and, for 6 patients, the dosage was 650 mg for 7 days. MEASUREMENTS: Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment. MAIN RESULTS: Neither zidovudine clearance nor production of the glucuronide conjugate of zidovudine was impaired after treatment with acetaminophen. Clearance of zidovudine was actually accelerated by 5%, 11%, and 33% with the three acetaminophen regimens, respectively (P = 0.002 by analysis of variance; P = 0.04 for linear trend when changes in the area-under-the-curve for zidovudine were compared). CONCLUSION: Because serum concentrations of zidovudine decrease after the coadministration of acetaminophen, a pharmacokinetic interaction between zidovudine and acetaminophen is unlikely to increase the risk for hematologic toxicity associated with zidovudine.     

Toxic effects of zidovudine in asymptomatic human immunodeficiency virus-infected individuals with CD4+ cell counts of 0.50 x 10(9)/L or less. Detailed and updated results from protocol 019 of the AIDS Clinical Trials Group.

BACKGROUND--Protocol 019 of the AIDS Clinical Trials Group is a multicenter, double-blind, placebo-controlled trial of zidovudine (3'-azido-3'-deoxythymidine; formerly AZT) in human immunodeficiency virus-infected asymptomatic individuals. The initial results in the stratum of subjects entering with CD4+ cell counts of 0.50 x 10(9)/L or less have been reported, but without a detailed analysis of toxic effects. METHODS--This detailed and updated report analyzes the toxic effects that occurred in 1567 subjects (91% men; 89% white) in this stratum of protocol 019 who received placebo (494 subjects), a 500-mg daily dose of zidovudine (544 subjects), or a 1500-mg daily dose of zidovudine (529 subjects). Hematologic, hepatic, and renal effects and patient-reported symptoms and clinical signs were monitored. RESULTS--Severe anemia (hemoglobin level, < 80 g/L) was associated with both the 500-mg zidovudine group and the 1500-mg group compared with placebo. The estimated 18-month risks of severe anemia were 0.4%, 2.0%, and 9.7% for the placebo, 500-mg zidovudine, and 1500-mg zidovudine groups, respectively. Predictive baseline measures were lower hemoglobin level in the 1500-mg group and the two zidovudine groups combined and lower platelet count in the 500-mg zidovudine group. The risk of a first severe anemia developing was greatest in months 3 through 8 of treatment. Of the 44 subjects with severe anemia in the zidovudine groups, 18 (41%) progressed from mild anemia (hemoglobin level, 95 to 109 g/L) to severe anemia on consecutive visits (usually 2 to 4 weeks apart). Severe neutropenia (absolute neutrophil count, < 750 x 10(6)/L) did not occur significantly more often in the 500-mg zidovudine group but did in the 1500-mg zidovudine group. Moderate neutropenia (absolute neutrophil count, < 1300 x 10(6)/L) did develop significantly more often in the 500-mg zidovudine group (165 subjects) than in the placebo group (71 subjects). Mild (or worse) elevations of bilirubin levels were uncommon but occurred more often with zidovudine. Severe nausea (and/or vomiting) was rare (2.8% of subjects) but was associated with zidovudine. Milder patient-reported events were common, and a number were associated with zidovudine. CONCLUSION--Zidovudine at the 500-mg/d dosage appears to be tolerable in many patients with asymptomatic human immunodeficiency virus infection and CD4+ cell counts of 0.50 x 10(9)/L or less. Increased clinical surveillance for anemia may be warranted in certain patients.     

Field acceptability and effectiveness of the routine utilization of zidovudine to reduce mother-to-child transmission of HIV-1 in West Africa

OBJECTIVE: To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission (MTCT) of HIV in breastfed children after a randomized clinical trial demonstrated its efficacy in C?te d'Ivoire and Burkina Faso. METHODS: Pregnant women aged 18 years or older, who had confirmed HIV-1 infection, haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36-38 weeks' gestation to receive an oral short course of zidovudine. Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction, or if aged 15 months or older, a positive HIV serology. RESULTS: The acceptability of HIV pretest counselling was significantly higher in the cohort (90.3%) than in the trial (83.7%) (P < 0.001), but the return rate for HIV test results and for inclusion was low. A similar proportion of women accepted starting zidovudine in the cohort, 30.4% compared with 27.3% in the trial (P = 0.13). The proportions of women who took more than 80% of the expected zidovudine regimen were 81.8% before labour, 86.7% during labour, and 88.1% during the postpartum period, compared with those observed during the trial, 78.1, 81.1, and 85%, respectively. The MTCT probability at age 15 months was 19.6% in the cohort (n = 185) versus 21.2% in the trial (P = 0.52). CONCLUSION: The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures. For women who consent, zidovudine is well accepted and efficacious under routine circumstances.     

Compliance with zidovudine therapy in patients infected with human immunodeficiency virus, type 1: a cross-sectional study in a municipal hospital clinic.

PURPOSE: To determine the extent of and clinical variables associated with zidovudine compliance. PATIENTS AND METHODS: A survey of 83 patients infected with human immunodeficiency virus (HIV) followed in a municipal hospital clinic was performed. Compliance histories were validated by serum and urine zidovudine levels. Patient characteristics included 46% white, 63% with a history of intravenous drug use, and 59% reporting a diagnosis of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The main outcome measure was greater than 80% compliance with prescribed doses of zidovudine over the previous week. RESULTS: Sixty-seven percent of the study patients reported greater than 80% compliance with prescribed doses of zidovudine over the previous week. The most common explanations given for missing a dose were "forgot to take zidovudine" and "did not have the medication with me." Five variables were independently associated with greater than 80% compliance as determined by stepwise multiple logistic regression: patient belief that zidovudine prolongs life (odds ratio [OR] 9.3, [95% confidence interval (CI) 2.4, 36.7]), a diagnosis of AIDS or ARC (OR 5.5, [CI 1.5, 20.4]), use of a medication timer (OR 4.4, [CI 1.0, 19.1]), no history of intravenous drug use (OR 3.7, [CI 1.0, 14.2]), and taking one to three other medications with zidovudine. CONCLUSIONS: High compliance with zidovudine was achieved by HIV-infected patients in a municipal hospital clinic, many of whom had a history of intravenous drug use. Compliance with zidovudine may be enhanced by a patient's belief that it prolongs life and the use of a medication timer for proper dosing.     

Zidovudine (AZT) for treatment of patients infected with human immunodeficiency virus type 1. An evaluation of effectiveness in clinical practice

To learn about the patterns of use and the effectiveness of zidovudine therapy in clinical practice, we conducted an observational cohort study of 86 patients with human immunodeficiency virus type 1 infection. All patients were followed up for at least 6 months after starting zidovudine (AZT) therapy. Of the 86 patients, 78 (91%) initially received full-dosage zidovudine (1200 mg/d), and eight received a reduced dosage (600 mg/d). During follow-up, the number able to maintain full-dosage zidovudine therapy decreased to 54 (63%) at 3 months and 40 (47%) at 6 months. Thirty-five patients required dosage reductions that lasted at least 7 days and were not preceded by an adverse outcome (death or opportunistic infection). Overall, adverse outcomes occurred for nine (26%) of those with dosage reductions compared with 22 (43%) of 51 patients with no previous dosage change. Even after adjusting for baseline cytopenias and the time of the dosage reductions, adverse outcomes did not occur significantly more often in patients who received reductions in their zidovudine dosage. Our results indicate that full-dosage zidovudine therapy cannot be maintained for most patients infected with human immunodeficiency virus, but that clinicians need not be pessimistic about treatment outcomes when dosage reductions are needed.     

Thai Red Cross zidovudine donation program to prevent vertical transmission of HIV: the effect of the modified ACTG 076 regimen

OBJECTIVES: To evaluate the impact of the modified ACTG 076 zidovudine regimen on the risk for vertical HIV transmission. DESIGN: Observational retrospective evaluation of a prospective cohort. SETTING: Thai Red Cross zidovudine donation program to reduce vertical HIV transmission. PATIENTS: HIV-infected Thai women and their offspring. INTERVENTION: The modified regimen consisted of 500 mg zidovudine daily during pregnancy and 300 mg zidovudine every 3 h during labor, taken orally, and 2 mg/kg zidovudine syrup four times daily for 6 weeks to infants. MAIN OUTCOME MEASURES: Only infants with at least 1 HIV DNA polymerase chain reaction (PCR) result at age > or = 4 weeks were included. HIV infection was defined by having at least one positive PCR at age > or = 4 weeks. The transmission rate was calculated. Characteristics of women who did and did not transmit HIV to infants were compared. RESULTS: A total of 2891 women and their infants participated in the program and 726 infants of 719 women were included in the analysis. Forty-three infants were infected. The overall transmission rate was 6.0% (95% confidence interval, 4.4-8.0). There were no differences in maternal characteristics between transmitters and non-transmitters. The transmission rate in women who started zidovudine before 30 weeks' gestation was not significantly different from that in women who started zidovudine at or after 30 weeks' gestation: 5.7 versus 3.3%, respectively. CONCLUSIONS: This modified zidovudine regimen is effective in reducing vertical transmission in a country with predominant subtype E infection. A donation program for preventing vertical HIV transmission can be implemented in developing countries, as in Thailand.     

HIV-seropositive thrombocytopenia: the action of zidovudine.

The action of zidovudine when administered to individuals with severe HIV thrombocytopenia was investigated. Four individuals with platelets less than 50 x 10(9)/l and CD4 cells greater than 200 x 10(6)/l were treated with 600 mg zidovudine per day for 6 weeks, no drug for 6 weeks, 1200 mg zidovudine per day for 6 weeks, then no drug for 6 weeks. Glycocalicin, a platelet protein which correlates inversely with platelet survival, was assayed before and after treatment. Glycocalicin indices were also measured in four additional individuals with HIV thrombocytopenia. Platelet counts rose 2.5-fold [95% confidence interval (Cl), 2.0-3.0)] for four subjects who received 600 mg zidovudine per day and 4.9-fold (95% Cl, 4.0-5.8) for three subjects receiving 1200 mg zidovudine per day. Platelet counts declined during drug-free intervals. Plasma glycocalicin indices were elevated in all with untreated HIV thrombocytopenia. Indices fell after zidovudine treatment in six of seven individuals, suggesting that zidovudine prolonged platelet survival. Analysis of 170 HIV-seropositive asymptomatic individuals [mean CD4 count 474 x x 10(6)/l, standard deviation (s.d.) 245 x 10(6)/l] revealed that 14 (8%) had less than 125 x 10(9)/l platelets but only 2 (1%) had less than 50 x 10(9)/l platelets. Platelet counts increased spontaneously in eight individuals with mild HIV thrombocytopenia among the 10 for whom repeat counts were available.     

Increased T-cell colony formation in AIDS patients treated with zidovudine: a possible mechanism for increased lymphocyte number

Treatment of AIDS patients with zidovudine is associated with an increase in lymphocyte counts. The mechanism for this increase is unclear and somewhat surprising in view of the myelosuppressive effect of zidovudine. To investigate this further, we measured lymphocyte numbers, T-cell subsets, and the ability of peripheral blood mononuclear cells (PBMC) to form T-cell colonies (T-CFC) in agar formation, in a group of patients with AIDS, before and during the first 6 months of zidovudine treatment. Eight patients were treated for an average of 11 weeks. There was a significant increase in T-CFC with zidovudine treatment (11.5 +/- 4.7% versus 29.8 +/- 6.9%, P less than 0.02 using a paired Student's t-test). There was a non-significant trend in the improvement of lymphocyte counts in these patients (872 +/- 117 versus 1102 +/- 204, NS). In vitro exposure of lymphocytes to zidovudine (200 mumol/l) resulted in modest suppression of T-CFC formation, suggesting that the effect of zidovudine treatment is indirect. Given that we have previously shown that inactivated HIV can inhibit T-CFC formation, we suggest that zidovudine treatment indirectly allows an increase in lymphocyte number by decreasing virus load, thereby permitting greater T-cell repopulation.     

Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of post-thrombotic treatment

In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0·1–0·4 × 10⁹/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0·2 × 10⁹/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0·2 × 10⁹/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0·75 × 10⁹ cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.     

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial

A study was conducted to assess the safety and efficacy of short-course nevirapine compared with zidovudine given to women during labor and to neonates during the first week of life. 626 HIV-1 infected pregnant women attending the antenatal clinic from November 1997 to April 1999 at Mulago Hospital in Kampala, Uganda, were randomly given nevirapine or zidovudine. Infants were tested for HIV-1 infection at birth, at 6-8 weeks, and at 14-16 weeks. Findings revealed that the estimated risk of HIV-1 transmission in the zidovudine and nevirapine groups was 10.4% and 8.2%, respectively, at birth; 21.3% and 11.9%, by 6-8 weeks; and 25.1% and 13.1%, by 14-16 weeks. There was a 47% relative efficacy rate of the nevirapine regimen at 14-16 weeks compared to zidovudine. Based on the findings, nevirapine lowers the risk of HIV-1 transmission by nearly 50% during the first 14-16 weeks of life in breast-fed infants.     

Zidovudine prophylaxis for needlestick exposure to human immunodeficiency virus

Objective:To perform a decision analysis to determine the thresholds of safety and effectiveness that would fustify short-term zidovudine (AZT) administration for persons with accidental percutaneous exposure to HIV-positive blood. Design:Published data were used to estimate the seroconversion rate (0.42%), rate of developing AIDS if HIV-infected (5%/year), and survival with AIDS (50%/year). No information is available on zidovudine effectiveness and little is known about fatal toxicity of zidovudine. Death from AIDS or from zidovudine toxicity was used as the endpoint. Results:For those with exposure to blood known to be HIV-seropositive, the benefits of zidovudine outweigh the risks if efficacy is above approximately 3% to 8%. Wide variations in the assumptions have little effect on the thresholds. Conclusions:Since clinical trials to determine zidovudine effectiveness in this setting will probably never be done, decision analysis offers the only quantitative method for addressing this question. Unless future studies show zidovudine to be both ineffective and toxic, the benefits of short-term administration of zidovudine outweigh the risks immediately after exposure to HIV-positive blood. Zidovudine benefits do not clearly outweigh the risks after exposure to blood of unknown serologic status, or if there is a delay in starting therapy. Received from the Clinical Trials Unit and the Departments of Medicine, Community Medicine, and Biomathematical Sciences, Mount Sinai School of Medicine of the City University of New York, New York, New York. Presented at the V International Conference on AIDS, Montreal, Quebec, Canada, June 1989. Supported in part by grant no. NOI-AI-72627 from the National Institute of Allergy and Infectious Diseases.     

Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine.

OBJECTIVE: To evaluate the development of phenotypic and genotypic resistance to zidovudine, didanosine and nevirapine as a function of the virologic response to therapy in a group of drug-naive individuals receiving various combinations of these agents. DESIGN: All patients were enrolled in a double-blind controlled randomized trial (the INCAS study) and were selected for detailed resistance studies based on specimen availability and virologic response. METHODS: Within the three study groups (zidovudine/nevirapine, zidovudine/didanosine or zidovudine/nevirapine/didanosine), 16, 19 and 24 patients, respectively, had evaluable baseline isolates and remained in the study > 24 weeks. Phenotypic resistance to all three drugs was evaluated using the VIRCO recombinant virus assay. Genotypic sequencing was done on selected specimens from patients receiving zidovudine/nevirapine/didanosine. RESULTS: After 24 weeks, all available isolates taken from patients receiving nevirapine were resistant to this agent, while 18/21 (86%) patients receiving triple therapy carried such isolates at 30--60 weeks. At 24 weeks, zidovudine resistance developed in 4/40 isolates but was more frequent after 30--60 weeks, especially in patients on two drugs. The degree of zidovudine resistance (rise in concentration required for 50% inhibition) appeared lower in the triple therapy group compared with zidovudine/didanosine (P = 0.0004). All nevirapine-resistant isolates that were sequenced carried at least one mutation associated with resistance, most often K103N and/or Y181C. CONCLUSION: The use of highly active drug therapies may be associated with a beneficial effect on the development of antiretroviral drug resistance. The characteristics of virologic suppression that must be maintained to avoid resistance are currently being studied in hypothesis-driven clinical trials.     

Factors influencing outcome of treatment with zidovudine of patients with AIDS in Australia. The Australian Zidovudine Study Group

In a multicentre study of zidovudine therapy in Australia commencing in June 1987, 308 homosexual or bisexual men with AIDS started on zidovudine by 30 June 1988. Using follow-up data collected through 31 December 1988, the outcome of the first 18 months of zidovudine therapy in these patients has been analysed in terms of efficacy, expressed as survival and as time to development of a new AIDS-defining condition, and in terms of safety, expressed as toxicity. Median survival from time of diagnosis of AIDS was 124 weeks, significantly longer (P less than 0.001, logrank statistic) than the median survival of 44 weeks in historical controls representing AIDS patients prior to the availability of zidovudine therapy. Median survival time from starting zidovudine has not been reached in these patients, while 172 (56%) developed new AIDS-defining conditions, with median time to progression of 48 weeks. Anaemia requiring transfusion was experienced by 155 patients (50%). Significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients who commenced zidovudine therapy (Dx-zidovudine time) within 12 weeks of diagnosis and had baseline Karnofsky scores greater than or equal to 80, haemoglobin greater than or equal to 11 g/dl, CD4+ cell counts greater than or equal to 50 x 10(6)/l. Therapy-related significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients with no weight loss and who received the full zidovudine dose (1.2g) during the first 52 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zidovudine treatment for anti-HIV positive haemophiliacs

Twenty haemophiliacs (17 CDC group IV and 3 CDC group II) were treated with zidovudine for a median of 37 weeks (range 10-66). Eight (40%) tolerated zidovudine without a dose change. Two patients died and five patients (29%) developed opportunist infections. Haematological toxicity occurred in ten CDC IV patients (59%) but only one case of sepsis occurred in 101 episodes of documented granulocytopenia. Thrombocytopenia responded to treatment with zidovudine in four of five patients. It is concluded that zidovudine is beneficial for symptomatic haemophiliacs and although the haematological toxicity is high, it is mostly asymptomatic, reversible and well tolerated. Two of the three CDC II patients treated with zidovudine progressed to CDC IV, but had low initial T4 lymphocyte counts and were P24 antigen positive.     

The antiviral effect of zidovudine and ribavirin in clinical trials and the use of p24 antigen levels as a virologic marker

The inhibition of viremia and p24 core antigenemia in patients infected with human immunodeficiency virus (HIV) was evaluated in separate multicenter, double-blind, placebo-controlled trials of zidovudine and ribavirin. Of 29 patients (14 with AIDS and 15 with AIDS-related complex [ARC]) enrolled in the zidovudine study, 16 received 250 mg of zidovudine every 4 h and 13 received placebo. No difference in HIV isolation from peripheral blood was observed at 20 w in treated versus placebo groups (79% vs. 82%). In patients tolerating zidovudine, mean p24 antigen levels dropped to 8.2% +/- 8.1% of their baseline values, whereas in placebo recipients mean p24 antigen levels declined to 61.3% +/- 40.8% of their baseline values (P less than .005). In the ribavirin study, patients with ARC treated with either 800 mg or 600 mg ribavirin daily or with placebo showed no consistent reduction in p24 antigenemia or decrease in HIV isolation. These data indicate that decline in p24 antigenemia can be a useful virologic marker in evaluation of new antiretroviral drugs.     

Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial

OBJECTIVES: To compare the incidence of clinical lipodystrophy in HIV-1-infected patients receiving zidovudine or stavudine, in combination with indinavir and lamivudine, in a randomized trial. METHODS: NOVAVIR was a randomized multicentre trial comparing stavudine/lamivudine/indinavir and zidovudine/lamivudine/indinavir in 170 patients pretreated with zidovudine, didanosine or zalcitabine (> 6 months), but naive for lamivudine, stavudine and protease inhibitors. The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of 101 patients after 30 months of follow-up. RESULTS: The incidence of lipoatrophy was increased in the stavudine arm versus the zidovudine arm, as followed: facial atrophy: 48 versus 22% of patients, P = 0.011, lower limb atrophy: 49 versus 22% of patients, P = 0.006, buttock atrophy: 47 versus 20% of patients, P = 0.009, venomegaly: 57 versus 24% of patients, P = 0.001. There was no significant difference in the incidence of clinical signs of central fat accumulation nor in fasting metabolic parameters at month 30 between the two arms. In multivariate analyses, the stavudine arm, previous therapy with didanosine, and a lower CD4 cell count at study entry were associated with an increased risk of lipoatrophy, whereas older patients and women had an increased risk of lipohypertrophy. CONCLUSION: Patients receiving stavudine/lamivudine/indinavir had a greater rate of clinical lipodystrophy, mainly lipoatrophy, than those treated with zidovudine/lamivudine/indinavir.     

Implementing short-course zidovudine to reduce mother-infant HIV transmission in a large pilot program in Thailand

OBJECTIVES: To describe a pilot mother-infant HIV prevention program started by the Ministry of Public Health of Thailand in July 1998 and to report on the first year of its implementation. DESIGN: Analysis of monthly summaries of data from project logbooks, simple data forms in antenatal clinics and delivery rooms, site visits and workshops, mail survey. SETTING: All 89 public hospitals in seven north-eastern provinces of Thailand. PARTICIPANTS: Childbearing women, program officials. INTERVENTIONS: Counseling and HIV testing for pregnant women, short-course antenatal zidovudine for HIV-infected pregnant women, and infant formula for their children. MAIN OUTCOME MEASURES: Proportion of women with HIV test, proportion of HIV-infected women receiving zidovudine. RESULTS: Of 75,308 women who gave birth between July 1998 and June 1999, 74,511 (98.9%) had antenatal care, 51,492 (69.1%) in the same district and 23,019 (30.9%) outside the district where they gave birth. HIV test results were available at delivery for 46,648 (61.9%) women, 410 (0.9%) of whom tested positive. Of these HIV-infected women, 259 (63.2%) participated in the zidovudine program and 6 (1.5%) received zidovudine from other sources. The proportion of women whose HIV test results were known and proportion of HIV-infected women who received zidovudine increased significantly during the year. CONCLUSIONS: A mother-infant HIV prevention program using short-course antenatal zidovudine was quickly implemented in a large region of Thailand with moderate HIV prevalence. This successful experience is leading to national implementation of a perinatal HIV prevention program in Thailand and may prompt other developing countries to start similar programs.