Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania

The objective of this study was to analyze the mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load at enrollment (36 weeks of gestation) in a cohort of HIV-1-seropositive breast-feeding women at the Dar es Salaam site of the multicenter Petra trial (a mother-to-child HIV-1 transmission intervention trial using antiretroviral therapy). Antiretroviral treatment was not available in this setting apart from the short treatment given within the trial around delivery to prevent mother-to-child transmission of HIV. T-lymphocyte subsets were determined by flow cytometry. Plasma HIV-1 RNA was quantified by the Amplicor HIV-1 RNA Monitor v 1.5 assay. Mortality after delivery was analyzed using the life-table technique and Cox regression. The analysis included 266 mothers. The CD4 cell counts at enrollment were <200 cells/mm in 14.5% of the mothers. The viral load at enrollment was >100,000 RNA copies/mL in 33.6% of the mothers. The mortality 24 months after delivery was 6.7% (95% CI = 3.1-10.1%). The mortality 24 months after delivery was 29.9% (95% CI = 13.1-46.9%) for mothers with <200 CD4 cells/mm at enrollment, 3.3% (95% CI = 0-6.6%) for mothers with 200-499 CD4 cells/mm, 2.9% (95% CI = 0-7.1%) for mothers with >500 CD4 cells/mm (P = 0.0000), 15.0% (95% CI = 6.6-23.4%) for mothers with viral load >100,000 copies/mL at enrollment, and 2.8% (95% CI = 0-5.6%) for mothers with viral load <100,000 copies/mL (P = 0.0000). In the multivariate analysis CD4 cell counts and viral load were both independent risk factors for mortality (P < 0.001 and P = 0.004, respectively). In conclusion, the mortality was high among women with severe immunosuppression or high viral load at enrollment, but not in the rest of the women. CD4 lymphocyte count in late pregnancy was a better predictor of death within 2 years than was viral load. The results support the World Health Organization recommendation to initiate antiretroviral treatment in resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.     

Advances in the prevention of mother-to-child transmission of HIV-1 infection in resource-limited settings

Ten years after the first trials demonstrating the efficacy of zidovudine (ZDV) for the prevention of mother-to-child transmission (pMTCT) of HIV, different antiretroviral approaches have been validated in resource-limited settings. Remarkable progress has been made in the last 4 years, with trials demonstrating the efficacy of postexposure antiretroviral prophylaxis in Malawi, as well as studies in Thailand and C?te d'Ivoire assessing the efficacy and viral resistance patterns of short-course regimens combining ZDV plus single-dose nevirapine (sdNVP). The field efficacy of a short course of ZDV plus lamivudine (3TC), together with sdNVP, has also been recently reported, with 6-week transmission rates below 5% for the first time in Africa in a population in which 40% breast-feed. The introduction of HAART for pregnant women has begun on a small scale in resource-limited settings and will hopefully further reduce transmission. What remains is the crucial issue of viral resistance after antiretroviral therapy for pMTCT, especially in the context of the growing availability and use of sdNVP in national pMTCT programs. Preliminary data from South Africa and C?te d'Ivoire suggest that the maternal use of ZDV plus 3TC for at least 3 days postpartum may reduce the occurrence of resistance mutations after maternal exposure to sdNVP. In the context of increasing controversy surrounding the use of sdNVP for pMTCT, the World Health Organization has recently reiterate its recommendations for its use for pMTCT in resource-constrained settings within a wide panel of antiretroviral regimens, in order to allow greater and quicker population coverage. The field application of pMTCT study results is a real challenge, and innovative approaches need to be designed an evaluated ot increase uptake of pMTCT programs in resource-poor settings. Research must continue to identify new interventions and new antiretroviral drugs for pMTCT.     

Effectiveness of repeat single-dose nevirapine for prevention of mother-to-child transmission of HIV-1 in repeat pregnancies in Uganda

BACKGROUND: Single-dose nevirapine (SDNVP) is widely used to prevent mother-to-child HIV transmission in resource-limited settings. Given detection of resistant mutants among women who receive SDNVP, concerns have arisen over the efficacy of SDNVP in repeat pregnancies. METHODS: Retrospective data were collected from SDNVP-exposed and -unexposed women from the HIV Network for Prevention 012 trial who subsequently received SDNVP in another pregnancy. Prospective data were collected from pregnant women who were SDNVP exposed or unexposed before delivery. Kaplan-Meier and Cox regression analyses were used to estimate rates of HIV infection and HIV-free survival among infants born to women with or without prior SDNVP exposure. RESULTS: In the retrospective cohort, the infection rates were 11.3% and 16.7% for 104 infants of NVP-exposed and -unexposed mothers, respectively (P = 0.41). In the prospective cohort, among 103 infants of NVP-exposed and -unexposed mothers, the 12-month infant HIV infection rates were 20.5% and 18.7% (P = 0.81) and HIV-free survival rates were 74.4% and 78.1% (P = 0.66), respectively. CONCLUSIONS: There was no increased risk of infant HIV infection among SDNVP-exposed women compared with -unexposed women. These findings support current international guidelines to offer SDNVP to HIV-infected pregnant women, regardless of previous SDNVP exposure, when more complex prophylaxis regimens are not available.     

Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding: from animal studies to randomized clinical trials

The major remaining challenge in the prevention of mother-to-child transmission is the reduction of the risk in settings where breast-feeding is common. This review gives an update on ongoing or planned antiretroviral intervention studies in resource-limited settings that are aimed at reducing the risk of mother-to-infant HIV transmission during lactation. These strategies include antiretroviral therapy given to the mother to reduce viral load in plasma and breast milk as well as antiretroviral regimens providing prophylaxis to uninfected infants during the period of breast-feeding. The rationale for the interventions based on animal models and human studies is described as well as the study designs of clinical trials. Potential risks and benefits of these interventions to mothers and infants are also highlighted. Laboratory studies nested within several of these trials will provide a better understanding of the pathogenesis of postnatal HIV transmission and its potential prevention using antiretroviral drugs.     

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants

OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in children by comparing the clinical outcome of infants born to HIV- 1-seropositive mothers who did versus those who did not receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS-related death before 18 months of age. RESULTS: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally infected infants born to HIV-infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.     

Efficient monitoring of HIV-1 vertically infected children in Kenya on first-line antiretroviral therapy

Background

Worldwide access to antiretroviral therapy (ART) in low- and middle-income countries has significantly increased. Although this presents better treatment options for HIV-infected individuals, the challenge of monitoring ART in these settings still remains.

Objective

To investigate efficient and cost-effective criteria for assessing ART failure among HIV-1-infected children on first-line ART in resource-limited settings.

Study design

Retrospective analysis of 75 HIV-1 vertically infected Kenyan children with a follow-up period of 24 months after initiating ART. Plasma viral load, peripheral CD4⁺T-cell counts and HIV-1 drug-resistance mutations were monitored biannually.

Results

Plasma viral load (VL) was suppressed to undetectable level or more than 1.5 log₁₀ from baseline levels in 53 (70.7%) children within 24 months. VL in the remaining 22 (29.3%) children was not suppressed significantly. Of the 22 children, 21 were infected with HIV-1 strains that developed drug-resistance mutations; 9 within 12 months and 12 between 12 and 24 months. Among the 53 who were successfully treated, VL was suppressed in 33 within 12 months and in 20 between 12 and 24 months. There was no significant difference in VL at baseline and the change of CD4⁺T-cell counts after initiating ART between those treated successfully and the failure groups.

Conclusion

After initiating ART, children may require longer times to achieve complete viral suppression. Plasma viral load testing 24 months after initiating ART could be used to differentiate ART failures among HIV-1 vertically infected children in resource-limited settings. Additionally, drug resistance testing, if affordable, would be helpful in identifying those failing therapy and in choosing second-line regimens.     

Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study

OBJECTIVE: To investigate the possibility of reducing mother-to-child transmission (MTCT) of HIV-1 through breast-feeding by prophylactic antiretroviral (ARV) treatment of the infant during the breast-feeding period. DESIGN: An open-label, nonrandomized, prospective cohort study in Tanzania (Mitra). METHODS: HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1 week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6 months). Counseling emphasized exclusive breast-feeding. HIV transmission was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial, taking CD4 cell count and other possible confounders into consideration. RESULTS: There were 398 infants included in the transmission analysis in the Mitra study. The estimated cumulative proportion of HIV-1-infected infants was 3.8% (95% confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI: 2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High viral load and a low CD4 T-cell count at enrollment were associated with transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to 11.4). No serious adverse events related to the ARV treatment of infants occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50% lower than in the breast-feeding population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The difference in transmission up to 6 months was significant also in the subpopulation of mothers with CD4 counts>or=200 cells/microL. CONCLUSIONS: The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health.     

Effect of cessation of zidovudine prophylaxis to reduce vertical transmission on maternal HIV disease progression and survival

Zidovudine prophylaxis is recommended to reduce perinatal HIV-1 transmission, but there are limited data on long-term effects on women's health. Pediatrics AIDS Clinical Trials Group (PACTG) 288 was a prospective observational study among US women randomized to zidovudine or placebo in PACTG 076 that was designed to evaluate and compare postpartum clinical, immune, and viral parameters between randomized treatment arms. Forty-eight percent (226/474) of eligible women enrolled in the study (mean follow-up of 4.1 years). Progression and time to AIDS or death were similar in both groups, observed in 21 (19%) zidovudine group women and 29 (25%) placebo group women (RR = 0.73, 90% CI: 0.46-1.17). No significant differences in CD4 lymphocyte count or HIV RNA levels were detected. Genotypic zidovudine resistance was detected in 10% of 156 women (9% of zidovudine group women and 11% of placebo group women). Based on our data, ZDV monotherapy could be considered as chemoprophylaxis to reduce perinatal HIV transmission for minimally symptomatic HIV-infected pregnant women with a low viral load and normal CD4 cell count who do not want to receive highly active antiretroviral therapy because of concern about potential side effects or who wish to reduce fetal exposure to multiple drugs during pregnancy.     

Maternal viral load,CD4 cell count and vertical transmission of HIV-1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998. © 1998 Wiley-Liss,Inc.     

Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.     

Prevention of mother-to-child transmission of HIV in Thailand: physicians' attitudes on zidovudine use, pregnancy termination, and willingness to provide care.

We administered a survey to Thai physicians, using regular mail, on their attitudes and practices regarding zidovudine (ZDV) use and pregnancy termination in HIV-infected pregnant women. We surveyed their willingness to care for these patients as well. In 1997, 79.5% of 480 respondents reported that they did not routinely use perinatal ZDV prophylaxis. Predictors of failure to use ZDV found to be significant in our logistic regression model included practice outside of Bangkok (odds ratio [OR] = 2.0), belief that ZDV is not cost effective (OR = 2.5), unfamiliarity with AIDS Clinical Trials Group (ACTG) 076 results (OR = 2.5), and failure to screen for HIV routinely (OR = 4.9). Elective abortion for HIV-infected women was advocated by 45.3% of respondents. Factors associated in multivariable analysis with this preference included specialty training in obstetrics/gynecology (OR = 1.8), practice inside Bangkok (OR = 2.0), male gender (OR = 1.9), and treatment of < or =2 HIV-infected patients yearly (OR = 1.8). A significant proportion of respondents described themselves as unwilling to perform pelvic examinations (19.2%), vaginal deliveries (30.7%), or cesarean deliveries (39.5%) on women who were known to be infected with HIV. We conclude that many Thai obstetric providers are reluctant to care for HIV-infected women, do not routinely use perinatal ZDV prophylaxis, and prefer to terminate pregnancies among HIV-infected patients. Physician education concerning the value of HIV screening and antiretroviral therapy in HIV-infected pregnant women is needed urgently in Thailand.     

Incidence of HIV-1 infection and effects of clinic-based counseling on HIV preventive behaviors among married women in northern Thailand

To determine the incidence of and risk factors for HIV-1 infection among married women in northern Thailand, we enrolled 779 seronegative women from family planning clinics and a postpartum ward in Chiang Rai, Thailand, from 1998 through 1999. Women were tested for HIV antibodies at 6 and 12 months after enrollment. They received HIV prevention counseling at enrollment and at each follow-up visit. Counseling covered partner communication, partner HIV testing, and condom use by steady partners. Effects of counseling were measured using standardized questionnaires. Follow-up rates were 94% at 6 months and 92% at 12 months. Only 1 woman seroconverted during the follow-up period, yielding an overall HIV incidence of 0.14 per 100 person-years. After receiving counseling, women reported significantly increased communication with husbands concerning HIV risk, HIV testing, and condom use during the first 6 months after enrollment; communication remained high for 6 to 12 months. Women reported a modest increase in HIV testing and consistent condom use by husbands. The risk for HIV transmission to women in steady relationships is low in northern Thailand. Although HIV prevention counseling promoted partner communication, its effects on HIV preventive behaviors were limited.     

Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission

OBJECTIVE: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. METHODS: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. RESULTS: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). CONCLUSIONS: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.     

Couples at risk: HIV-1 concordance and discordance among sexual partners receiving voluntary counseling and testing in Uganda

OBJECTIVE: To determine correlates of HIV-1 concordance for couples receiving voluntary HIV counseling and testing. DESIGN: Cross-sectional study of couples receiving voluntary HIV counseling and testing in Kampala, Uganda. METHODS: An interview and physical examination were conducted for 49 HIV-1-concordant (both partners infected with HIV) and 126 HIV-1-discordant (1 partner infected with HIV and 1 partner HIV negative) couples. Blood samples from all participants were tested for HIV-1 and syphilis serology. CD4 cell count and HIV load were characterized for all HIV-infected persons. Urine samples were tested for Neisseria gonorrhoeae and Chlamydia trachomatis using ligase chain reaction. Associations between couples' HIV status and key sociodemographic, behavioral, and biomedical factors were analyzed. RESULTS: Men in HIV-concordant couples were more likely than men in HIV-discordant couples to be living together with their sexual partner (odds ratio [OR], 11.3; 95% confidence interval [CI], 2.8-53.7; P=0.004), to be uncircumcised (OR, 4.5; 95% CI, 1.1-18.8; P=0.042), and to have higher HIV loads (OR for each log increase, 3.0; 95% CI, 2.0-4.7; P<0.001). Women in HIV-concordant couples were more likely than women in HIV-discordant couples to be living together with their sexual partner (OR, 19.0; 95% CI, 3.8-84.8), to have an uncircumcised male partner (OR, 6.5; 95% CI, 1.6-26.4), to have had a sexually transmitted disease in the 6 months before enrollment (OR, 1.9; 95% CI, 0.9-4.5), and to have higher HIV loads (OR for each log increase, 2.2; 95% CI, 1.5-3.2). CONCLUSIONS: Several behavioral and biologic risk factors were associated with HIV concordance for couples. Providing early sexually transmitted disease diagnosis and treatment, antiretroviral therapy, and specially designed counseling to HIV-discordant couples may help prevent HIV transmission in couples where being in a stable sexual relationship is a major risk factor for HIV infection.     

Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United StatesRevised November 3, 2000

Abstract

These recommendations update the February 25, 2000 guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission.* This report provides health-care providers with information for discussion with HIV-1 infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented as scenarios and the factors influencing treatment considerations are highlighted in this report. It is recognized that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving. The Perinatal HIV Guidelines Working Group will review new data on an ongoing basis and provide regular updates to the guidelines; the most recent information is available on the HIV/AIDS Treatment Information Service (ATIS) website (http://www.hivatis.org).

In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1 infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy, pregnancy is not a reason to defer standard therapy. The use of antiretroviral drugs in pregnancy requires unique considerations, including the potential need to alter dosing as a result of physiologic changes associated with pregnancy, the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness for reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily to treat HIV-1 infection, to reduce perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy for infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen.