Use Of Zidovudine Research Articles

Incubation period of HIV-1 in perinatally infected children. New York City Perinatal HIV Transmission Collaborative Study Group.

To estimate the distribution of the incubation period of HIV-1 among perinatally infected children and to test the hypothesis that this distribution has been changing over time. An analysis of 190 perinatally HIV-1-infected children born between 1986 and 1997 in eight medical centers in New York City to women enrolled in a prospective cohort study. Non-parametric Kaplan-Meier method and parametric survival analysis. Using the Kaplan-Meier method it was estimated that among perinatally HIV-1-infected children, 48% [95% confidence interval (CI), 41-56] developed AIDS by 3 years of age after which the rate was less than 3% per year. Using a parametric survival analysis for extrapolation, it was predicted that 33% (95% CI, 23-43) would remain AIDS-free at 13 years of age. Median age at onset of AIDS was estimated to be 4.1 years (95% CI, 1.9-6.4) by parametric survival analysis. The year of birth was significantly associated with AIDS-free survival, suggesting an increase in the time to AIDS over the years. This association remained significant (P=0.03) after adjustment for those maternal characteristics that have also changed over time: timing of enrollment (prepartum versus postpartum), zidovudine, alcohol, and hard drug (heroin, cocaine or methadone) use during pregnancy. Although a substantial proportion of perinatally HIV-1-infected children develop AIDS very early in life, a significant and increasing percentage of them are expected to survive into adolescence without developing AIDS. Further research is needed to determine the factors associated with the lengthening survival to AIDS.

HIV, maternal anemia and perinatal intervention using zidovudine

International Journal of Gynecology & ObstetricsVolume 61, Issue 1 p. 65-66 Brief communications HIV, maternal anemia and perinatal intervention using zidovudine N. Meda, Corresponding Author N. Meda griv.muraz@fasonet.bf Centre MURAZ, Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies (OCCGE), Bobo-Dioulasso, Burkina Faso, FranceCorresponding author. Tel.: +27 226 972630; fax: +27 226 970177.Search for more papers by this authorB. Dao, B. Dao Department of Gynecology and Obstetrics, Centre Hospitalier National Sourô Sanou, Bobo-Dioulasso, Burkina Faso, FranceSearch for more papers by this authorA. Ouangré, A. Ouangré Centre MURAZ, Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies (OCCGE), Bobo-Dioulasso, Burkina Faso, France1 The DITRAME Study Group is organized as follows: Coordination: INSERM U 330, Université Victor Segalen Bordeaux 2, Bordeaux, France (François Dabis). Principal investigators: Maternité Cochin Port-Royal, Paris, France (Laurent Mandelbrot), Centre Hospitalier Universitaire de Yopougon, Abidjan, Côte d'Ivoire (Christiane Welffens-Ekra). Abidjan Center (Côte d'Ivoire): CeDReS, Centre Hospitalier Universitaire de Treichville (Patrice Combes, Fatoumata Sylla-Koko, Dominique Bonard, Bruno You); Centre Hospitalier Universitaire de Yopougon (Marguerite Timité); DITRAME Project (Rosa Ramon); ORSTOM Petit Bassam (Philippe Msellati). Bobo-Dioulasso Center (Burkina Faso): Centre MURAZ/OCCGE (Michel Cartoux, Lucile Gautier-Charpentier, Nicolas Meda, Amadou Ouangré, Arlette Simonon); Centre Hospitalier National Sourô Sanou (André Jules Bazié, Blami Dao, Boubacar Nacro, François Tall). Methodology: INSERM U 330, Bordeaux, France (Valériane Leroy, Roger Salamon); Centre MURAZ/OCCGE (Philippe Van de Perre); Laboratoire de Virologie, Hôpital Necker-Enfants Malades, Paris, France (Christine Rouzioux). The DITRAME project was established in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso) with grants from the Agence Nationale de Recherches sur le SIDA (ANRS) and the French Ministry of Cooperation within the ANRS Coordinated Action n∘ 12 in collaboration with the National AIDS Control Programmes of Cote d'lvoire and Burkina Faso.Search for more papers by this authorThe DITRAME Study Group (ANRS 049 Clinical Trial), The DITRAME Study Group (ANRS 049 Clinical Trial)Search for more papers by this author N. Meda, Corresponding Author N. Meda griv.muraz@fasonet.bf Centre MURAZ, Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies (OCCGE), Bobo-Dioulasso, Burkina Faso, FranceCorresponding author. Tel.: +27 226 972630; fax: +27 226 970177.Search for more papers by this authorB. Dao, B. Dao Department of Gynecology and Obstetrics, Centre Hospitalier National Sourô Sanou, Bobo-Dioulasso, Burkina Faso, FranceSearch for more papers by this authorA. Ouangré, A. Ouangré Centre MURAZ, Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies (OCCGE), Bobo-Dioulasso, Burkina Faso, France1 The DITRAME Study Group is organized as follows: Coordination: INSERM U 330, Université Victor Segalen Bordeaux 2, Bordeaux, France (François Dabis). Principal investigators: Maternité Cochin Port-Royal, Paris, France (Laurent Mandelbrot), Centre Hospitalier Universitaire de Yopougon, Abidjan, Côte d'Ivoire (Christiane Welffens-Ekra). Abidjan Center (Côte d'Ivoire): CeDReS, Centre Hospitalier Universitaire de Treichville (Patrice Combes, Fatoumata Sylla-Koko, Dominique Bonard, Bruno You); Centre Hospitalier Universitaire de Yopougon (Marguerite Timité); DITRAME Project (Rosa Ramon); ORSTOM Petit Bassam (Philippe Msellati). Bobo-Dioulasso Center (Burkina Faso): Centre MURAZ/OCCGE (Michel Cartoux, Lucile Gautier-Charpentier, Nicolas Meda, Amadou Ouangré, Arlette Simonon); Centre Hospitalier National Sourô Sanou (André Jules Bazié, Blami Dao, Boubacar Nacro, François Tall). Methodology: INSERM U 330, Bordeaux, France (Valériane Leroy, Roger Salamon); Centre MURAZ/OCCGE (Philippe Van de Perre); Laboratoire de Virologie, Hôpital Necker-Enfants Malades, Paris, France (Christine Rouzioux). The DITRAME project was established in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso) with grants from the Agence Nationale de Recherches sur le SIDA (ANRS) and the French Ministry of Cooperation within the ANRS Coordinated Action n∘ 12 in collaboration with the National AIDS Control Programmes of Cote d'lvoire and Burkina Faso.Search for more papers by this authorThe DITRAME Study Group (ANRS 049 Clinical Trial), The DITRAME Study Group (ANRS 049 Clinical Trial)Search for more papers by this author First published: 21 June 1999 https://doi.org/10.1016/S0020-7292(98)00016-2Citations: 14 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume61, Issue1April 1998Pages 65-66 RelatedInformation

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. Perinatal AIDS Collaborative Transmission Studies.

To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.

To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. Prospective study. Obstetric and paediatric clinics in Switzerland. Children of mothers with HIV infection identified before or at delivery. Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. HIV infection status of children. In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Perinatal HIV-1 transmission in the United States and internationally: A review

Summary Mother-to-infant transmission is the primary route of HIV-1 infection in children worldwide. Whereas the rate of perinatal transmission in the U.S. has dramatically decreased from 25% to 5–10% since 1994, due to widespread maternal and infant zidovudine (ZDV) use during pregnancy and post-delivery, such treatment is not feasible for most developing countries, where the large majority of HIV infected individuals reside. In developing countries, 20–40% of infected pregnant mothers continue to transmit to their babies, and 5–7 million children will have been infected worldwide by the year 2000. Epidemiologic studies have identified multiple potential risk factors for transmission, including low maternal CD4+ count, high viral load, STDs, low vitamin A levels, prolonged duration of rupture of membranes, chorioamnionitis, vaginal and preterm ( in utero transmission, also need further evaluation.

Update: Perinatally Acquired HIV/AIDS—United States, 1997

PERINATAL TRANSMISSION of human immunodeficiency virus (HIV) accounts for virtually all new HIV infections in children.¹Through 1993, an estimated 15,000 HIV-infected children were born to HIV-positive women in the United States.²In 1994, clinical trials demonstrated a two-thirds reduction in the risk for perinatal transmission associated with treatment of HIV-infected pregnant women and their infants with zidovudine (ZDV) therapy.³The Public Health Service (PHS) issued guidelines for the use of ZDV to reduce perinatal transmission in August 1994 and for universal HIV counseling and voluntary testing of pregnant women in July 1995.^3,4This report describes increases in HIV testing and use of ZDV treatment among HIV-infected mothers and a continued substantial decline in the incidence of acquired immunodeficiency syndrome (AIDS) during 1992-1996 among children who were infected through perinatal HIV transmission.^5* For states that conduct HIV surveillance, characteristics were examined for children born to

Relationship between CD4 count and CD4% in HIV-infected people.

To describe the relationship between absolute CD4 count and CD4%, and the influence on this of gender, risk group, age, a diagnosis of AIDS, use of zidovudine (ZDV) therapy and PCP prophylaxis. 9203 paired serial measurements of CD4 count and CD4% on 1017 initially AIDS-free and ZDV-naive HIV positive patients from a London-based cohort were available for analysis. Multi-level regression procedures were used on log-transformed data to relate values of CD4 count to a given level of CD4%. We estimated the effect of selected covariates on this relationship from the exponent of the covariate coefficient. A strong linear relationship was found between log CD4 and log CD4%, CD4 = e 1.78(CD4%)1.26 or 5.93 (CD4%)1.26 (excluding covariates). Based on this model, a CD4% of 5%, 15%, and 30% corresponded to an estimated CD4 count (95% confidence interval [CI]) of 45 cells/mm3 (17-117 cells/mm3), 182 cells/mm3 (64-499 cells/mm3) and 438 cells/mm3 (132-1395 cells/mm3), respectively. However, after adjustment for selected covariates, the predicted CD4 count for a given CD4% was found to be lower among heterosexuals and injecting drug users as compared with homosexual men by 30% and 17% respectively; following an AIDS diagnosis by 21%; and after initiation of ZDV therapy and PCP prophylaxis by 19% and 10%, respectively. This analysis should be useful to clinicians and researchers in relating values of CD4 count to CD4%, although we have demonstrated that this is not a simple relationship. The wide CI observed in the estimated CD4 count particularly at high CD4% values, and the adjustments necessary according to risk group, following an AIDS diagnosis and use of ZDV and PCP therapy limit its application in the clinical setting.

Effect of Treatment with Zidovudine on Subsequent Incidence of Kaposi's Sarcoma

Despite much investigation of zidovudine, little has been reported regarding its effect on the development of most individual AIDS-defining illnesses, including Kaposi's sarcoma (KS). We used observational data from the Multicenter AIDS Cohort Study (MACS) to estimate the effect of zidovudine use on the subsequent incidence of KS. To do this, we examined and adjusted for predictors of zidovudine use. CD4 lymphocyte counts, the development of HIV-related symptoms and AIDS, and changes in these factors were important predictors of zidovudine use. We used these associations to control for confounding by these and other factors with the G-estimation approach. We found no evidence that zidovudine use affected the time to KS in the MACS; the point estimate (95% confidence interval [CI]) for increase in time to KS was zero (-28%-68%). The relative risk was 1.0 (95% CI, 0.54-1.84). Randomized trials suggest that zidovudine may prevent KS. We discuss possible explanations for differences between results.

Paediatric HIV update.

Less than half of the paediatric HIV infections recorded in Australia have resulted from perinatal transmission, but in recent years this has been the predominant mode of infection. There are 136 infants who are known to have been exposed perinatally to HIV in Australia: 49 of these are infected. Caesarean section is thought now not to reduce the risk of perinatal transmission (PNT); rather, the risk increases with duration of membrane rupture and rises rapidly after 4 h of membrane rupture. However, no data exist to show that interventions to expediate delivery after membrane rupture reduce the risk of PNT. Data such as these suggest that the majority of perinatal infections (probably about 60%) occur close to the time of delivery. While the overall risk of PNT for non-breast fed infants is approximately 20-25%, the risk of infection for the infant is considerably increased when there is evidence of increased maternal viral burden. Advanced maternal disease predicts that if the infant is infected there is more likely to be early progression of HIV than is the case for the less frequently infected infants of mothers who are asymptomatic. Bottle feeding may prevent infection of 10% of children exposed perinatally. Use of zidovudine by the mother in the third trimester and i.v. zidovudine during labour, followed by oral zidovudine for the infant for 6 weeks can reduce the PNT rate by two thirds, to about 8%. Approximately 3% of uninfected infants with perinatal HIV exposure may be found to be transiently virus positive but eventually become antibody negative and thus appear to have eliminated the virus. The risk of Pneumocystis carinii pneumonitis (PCP) cannot be predicted on the basis of CD4 count and it is recommended that all children of infected mothers commence PCP prophylaxis around the age of 6 weeks-2 months and continue that therapy until the age of 12 months or until it becomes clear that the infant is uninfected. The cumulative risk of AIDS increases rapidly during the first year of life to about 20%, then more slowly at a rate of about 2 or 3% a year. The shape of this curve reveals the bimodal progression of HIV disease in children. About 15-20% of children rapidly develop a severe immune deficiency, opportunistic infections and, in most cases, encephalopathy. There is a very high morbidity rate in this group of children, most of whom die before the age of 3 or 4 years. In contrast, 80-85% of children only become immunodeficient after a relatively long period, which is similar to or perhaps even longer than that in adults. Recent studies indicate that zidovudine antiviral monotherapy is no longer appropriate. While no clear alternative to monotherapy has emerged most would, wherever possible, commence antiretroviral therapy with a combination of two or three drugs including zidovudine plus didanosine or lamivudine. If a third drug is used it would probably be a protease inhibitor.

Preventing transmission of blood-borne pathogens: A compelling argument for effective device-selection strategies

Disease transmission from percutaneous injury occurs in 2% to 40% of the health care workers (HCWs) after exposure to the hepatitis B virus (HBV), in 3% to 10% after exposure to the hepatitis C (HCV) virus, and in 0.2% to 0.5% after exposure to the HIV virus. According to a recently published case-control study from the Centers for Disease Control and Prevention, the following factors increase the risk of HIV seroconversion in HCWs after percutaneous exposure to HIV-infected blood: deep injury, visible blood on the device, procedures involving needle placement directly into a vein or artery, and terminal AIDS in the source patient. Postexposure use of zidovudine by HCWs appears to reduce the risk of HIV transmission by 79%. Institutions seeking to reduce the risk of HCW seroconversion should conduct analyses of specific tasks associated with these high-risk factors, and safety interventions should be installed when tasks and devices increase the risk of seroconversion. Although this type of outcome-based strategy may not significantly reduce the total number of needlestick injuries, reducing high-risk exposures minimizes disease transmission and maximizes the costeffectiveness of the intervention.

Prevention of vertical HIV transmission with zidovudine: Projected impact of HIV testing and prenatal care

We sought to estimate the impact of maternal HIV testing and prenatal care on the potential to reduce vertical transmission through zidovudine (AZT) use by HIV-infected mothers. We evaluated the prepartum maternal HIV diagnosis rate, prenatal care, disease stage, and vertical transmission rate (from a two-part mixture model) using New York State Medicaid and vital statistics data for HIV-infected mothers and their singletons in 1985-90. We used published data to estimate the effect of AZT on vertical transmission and expert input to define other parameters for the model. Our HIV-infected (N = 1514) had a vertical transmission rate of 27.0%. HIV was diagnosed prepartum for 39.5% of women in 1990. Transmission would have been 22.2% if AZT had been taken only by the subset of women diagnosed prepartum with HIV and receiving prenatal care by 34 weeks gestation (86.7%). Transmission would have dropped to 11.2% if all women had been diagnosed prepartum with HIV and received adequate prenatal care. The observed deficiencies in prenatal care and maternal HIV diagnosis rates in this Medicaid population-based cohort must be addressed to realize the promise of AZT to reduce vertical transmission.

Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3.

The objective of this study was to identify prognostic factors for survival in patients with pretreatment CD4 < or =50 cells/mm3 treated with nucleoside analogs, and to develop and validate a mortality risk model based on these factors. The design of the study consisted of retrospective analysis of AIDS Clinical Trials Group (ACTG) protocols 116a, 116b/117, 155, and 118. The setting was the multicenter AIDS Clinical Trials Group. The patients were HIV-infected with pretreatment CD4 < or =50 cells/mm3 and various degrees of prior zidovudine (ZDV) use. Double-blind, three-arm randomized control trials ACTG 116a and ACTG 116b/117 compared ZDV with didanosine (ddI). ACTG 155 compared ZDV with zalcitabine or combination therapy. Our validation study, ACTG 118, compared the effects of three different doses of ddI on survival. The main outcome measures were survival and mortality. The three studies combined enrolled 699 patients with entry CD4 T-lymphocyte counts of < or =50 cells/mm3. Forty percent of patients died during follow-up, with a median survival of 19.7 months. Multivariate analysis showed shorter survival at p < 0.0001 with lower CD4 count (relative hazard [RH] = 0.98) and lower hemoglobin level (RH = 0.81). Other factors included older age (RH = 1.03), male gender (RH = 1.70), Hispanic ethnicity (RH = 1.68), and symptomatic disease stage (RH = 2.06). Our predictive mortality risk model differentiated well patients with differing risks of mortality. When the risk model was applied to ACTG 118, the validation data set, the identified prognostic factors could distinguish patients with varying risks of death (p < 0.001, stratified log-rank test). These results demonstrate that CD4 T-lymphocytes counts < or =50 cells/mm3 should not be considered a precursor of imminent death; considerable variability in survival exists in severely immunocompromised patients. Our identification of prognostic indicators for survival can aid clinicians and patients in management of their disease and researchers in design of future clinical trials.

The future of prenatal HIV testing.

The use of zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus, as well as continuing advances in our understanding of the determinants of that transmission, and of potential new avenues of intervention augur ever more efficient perinatal prevention strategies in the near future. In this paper the evolving role of prenatal testing in an era of ever more successful interventions will be discussed. At least four factors will be critical in determining what that role will be: clinical, legal, ethical and economic. Each of these are parochial, i.e. they will feature in eradication strategies in different ways in different geographical, economic and cultural settings. An understanding of these factors will help to suggest what course testing policy should take and to determine the role clinicians must play if any testing policy is to succeed in contributing to the end of pediatric HIV disease.

Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland.

To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. HIV-infected pregnant women and children in the United Kingdom and Ireland. Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

Reducing the risk of perinatal HIV‐1 transmission with zidovudine: results and implications of AIDS Clinical Trials Group protocol 076

This paper reviews the rationale for the AIDS Clinical Trials Group (ACTG) protocol 076 design, the study results and the implications of these results, including discussion of the US Public Health Service Task Force recommendations on the use of zidovudine to reduce perinatal transmission and for prenatal human immunodeficiency virus (HIV) counseling and testing.

Progress in prevention of perinatal HIV-1.

The findings of a recent human immunodeficiency (HIV-1) prevention trial in the USA demonstrated that administration of an antiretroviral drug, zidovudine, to mothers during the prenatal and intrapartum periods, and to their neonates for 6 weeks, resulted in a two-thirds reduction in risk of perinatal transmission from 25.5% to 8.3%. These results were rapidly disseminated both in the USA and internationally. Since the release of these clinical trial results in the spring of 1994, several observational studies have documented a sharp increase in maternal and neonatal zidovudine use, as well as a significant decrease in perinatal HIV-1 transmission, with rates of about 8% being observed in non-clinical trial settings. Internationally, the results have led to the development of a variety of perinatal prevention trials that build on the success of the U.S. perinatal prevention trial but use modified strategies that can feasibly be carried out in developing countries.

Prevalence and incidence of resistance to zidovudine and other antiretroviral drugs

Drug-resistant human immunodeficiency virus (HIV)-1 has been detected in patients on all of the currently available antiretroviral drug regimens. Continuous, high-level virus replication with an error-prone reverse transcriptase enzyme and potential viral recombination events lead to each patient having numerous viral quasispecies and promote the emergence of drug-resistant strains. Drug resistance is associated with one or more point mutations in the HIV gene of the protein that is targeted by the drug. Factors associated with rapid emergence of drug resistance include host factors, such as advanced HIV disease and low CD4 cell counts; viral factors, such as high plasma HIV RNA, pre-existing drug-resistant virus, and possibly syncytium-inducing (SI) phenotype; and drug-related factors, such as suboptimal drug levels or poor compliance. High-level drug resistance has emerged after weeks to months of therapy for lamivudine (3TC) and nevirapine where drug-resistant quasispecies pre-exist in essentially all patients. Resistance has emerged more slowly for zidovudine (ZDV) and HIV protease inhibitors, which require the sequential accumulation of multiple mutations to develop high-level resistance. Certain drugs, such as didanosine (DDI), dideoxycytidine (DDC), and stavudine (D4T) have only produced viruses with low-level resistance, despite prolonged therapy. Development of drug-resistant HIV-1 has been associated with declining CD4 cell counts and rising plasma viral load. Zidovudine-resistant HIV-1 has been associated with adverse clinical outcomes independent of baseline CD4 cell counts and plasma HIV-1 RNA levels. Combination therapy offers the possibility of delaying or preventing the development of HIV drug resistance via interacting drug resistance mutations or potent antiviral activity. Widespread use of ZDV has been associated with transmission of ZDV-resistant HIV-1 in approximately 10% of adult seroconverters and a significant percentage of infants who fail the AIDS Clinical Trial Group (ACTG) 076 prophylactic regimen.

Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood — France, United Kingdom, and United States, January 1988–August 1994

Health-care workers (HCWs) are potentially at risk for human immunodeficiency virus (HIV) infection through occupational exposures to blood. Although prospective studies indicate that the estimated risk for HIV infection after a percutaneous exposure to HIV-infected blood is approximately 0.3% (1,2), factors that influence this risk have not been determined. To assess potential risk factors, CDC, in collaboration with French and British public health authorities, conducted a retrospective case-control study using data reported to national surveillance systems in the United States, France, and the United Kingdom. This report describes the study and summarizes results that suggest that risk factors for HIV transmission include certain characteristics of the exposure and the source patient; in addition, postexposure use of zidovudine (ZDV) by HCWs was associated with a lower risk for HIV transmission.

HIV Testing of Pregnant Women in Colorado 455

Background In Colorado there are 0.4 per 1000 HIV-infected women of childbearing age compared to a national prevalence of 1.6 per 1000 women. The ACTG 076 study demonstrated a reduction in vertical transmission of HIV to newborns with the use of zidovudine. The US Public Health Service has recommended routine HIV counseling and voluntary testing for all pregnant women and Congress has amended the Ryan White CARE Act to require that at least 95% of pregnant women have been tested for HIV. Objectives: Describe: 1) provider practices of HIV testing and counseling of pregnant women 2) provider attitudes towards HIV testing of pregnant women 3) the barriers providers perceive to HIV testing of pregnant women 4) provider knowledge about the use of zidovudine to decrease vertical transmission of HIV. Methods: Cross-sectional survey mailed to family practitioners, obstetricians, and nurse midwives who provide prenatal care to pregnant women in Colorado. Data entry and statistical analysis with Epi Info 6.04. Results: Overall response rate of health care providers surveyed was 48%; 120 obstetricians and 197 family practitioners that provided prenatal care were evaluable. Greater than 90% of providers test for HIV infection in pregnant women yet only half always test. Twenty five percent of providers do not test for HIV because they perceive their patients to be without risk factors. When offered HIV testing 90% of women will accept. Half of all providers are very uncomfortable with caring for HIV-infected women and overall only 30% have ever cared for an HIV-infected pregnant woman. Only 75% of providers are familiar with the use of zidovudine to interrupt vertical transmission of HIV to the newborn. Seventy five percent of providers feel that all pregnant women should be tested for HIV regardless of stated risk behaviors. Conclusions: Greater than 90% of providers state they test for HIV infection in pregnant women; 75% think all pregnant women should be tested regardless of risk factors yet only 50% of providers always test. Despite public health education efforts, 25% of health care providers that provide prenatal care in Colorado do not regularly test all pregnant women for HIV infection and 25% do not know about the use of zidovudine to interrupt vertical transmission of HIV to the newborn.

Survival of European patients with Kaposi's sarcoma as AIDS-defining condition during the first decade of AIDS. AIDS in Europe Study Group.

To determine whether the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has changed between 1979 and 1989; and to define whether prognosis factors could be identified. This is a multicentric retrospective cohort study from 52 centers in 17 European countries involving adults AIDS patients diagnosed between 1979 and 1989. Variables such as age, sex, geographical regions, transmission groups, date of Kaposi's sarcoma diagnosis, zidovudine use, CD4+ cell count and concomitant opportunistic infections or AIDS-related malignancies were evaluated by using uni- and multivariable proportional hazard models. Log-rank tests were used to determine which variables were associated with survival. From the 6,546 AIDS patients recruited in the database of the AIDS in Europe Study Group, 1,394 were diagnosed with Kaposi's sarcoma at the time of AIDS diagnosis, from 1979 and 1989. A total of 1,047 Kaposi's sarcoma patients died during the follow-up period. By Kaplan-Meier analyses, the median and mean survival for these Kaposi's sarcoma patients were 17 and 25 months, respectively, with no change over time. However, age, sex (female), geographic region, low CD4+ cell count (< 150 x 10(6)/l) and some opportunistic infections and non-Hodgkin's lymphoma were associated with a poorer prognosis. Zidovudine use, year of diagnosis and risk factor for HIV-1 infection brought no additional information as predictor of mortality. This study suggests that the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has remained poor during the last decade in contrast with the overall AIDS survival which had significantly improved from a median of 13-18 months during the same period of observation. There is a need for further prospective information to explain the worse prognosis in women and the geographical variations.