Genotypic resistance testing in HIV-infected pregnant women in an urban setting.

This study examines the utility of HIV genotypic resistance testing (GT) in pregnant women at their initial pregnancy evaluation. A retrospective medical record review of 50 consecutive HIV-infected pregnant women in whom GT was obtained in the Bronx, New York was conducted. Twenty-eight (56%) were antiretroviral experienced, including 12 on antiretroviral therapy (ART) at time of GT. Major mutations were found in 11 (24%) of 45 amplifiable GTs. Major resistance mutations were identified against nucleoside reverse transcriptase inhibitors (NRTIs) in six (13%) patients; against non-nucleoside reverse transcriptase inhibitors (NNRTIs) in eight (18%) patients, and against protease inhibitors in two (4%) patients. Duration of ART exposure was significantly associated with identification of resistance mutations by GT for NRTIs and NNRTIs (P < or =0.05). Results of this study indicate that GT at presentation may have implications on the initial choice of ART in up to one-quarter of HIV-infected pregnant women, especially with current or prior antiretroviral use.

Management of HIV infection during pregnancy.

Optimal management of HIV infection in pregnancy requires maternal use of potent antiretroviral therapy to prevent disease progression in the mother and vertical transmission to the newborn. Combination antiretroviral therapy substantially reduces the risk of perinatal HIV transmission and appears to be more effective than zidovudine monotherapy. The administration of single dose nevirapine to mother intrapartum and infant postpartum effectively reduces vertical HIV transmission and is less costly and cumbersome than zidovudine regimens. Elective cesarean section reduces vertical transmission of HIV but its benefit is less clear when antiretroviral therapy decreases maternal plasma HIV viral load to low levels at delivery. If possible, HIV-infected mothers should avoid breastfeeding. The present review discusses the importance of early identification of maternal HIV infection, strict adherence to combination antiretroviral regimens to prevent drug resistance, developing a better understanding of antiretroviral pharmacokinetics in pregnancy and short/long term safety of anti-HIV drugs.

Prevention of perinatal HIV transmission during pregnancy.

Transmission of the human immunodeficiency virus (HIV) from mother to child can occur in utero, during labour or after delivery from breastfeeding. The majority of infants are infected during delivery. Maternal HIV-1 plasma viral load at delivery is the most important predictor of vertical transmission. For this reason, efforts to interrupt transmission have focused on the use of antiretroviral therapy. Zidovudine has been shown to reduce significantly vertical HIV transmission when used antepartum and intrapartum by the mother and postpartum by the newborn for 6 weeks. However, zidovudine monotherapy increases the risk of developing zidovudine resistance and may jeopardize the goal of durable viral suppression and allow HIV disease progression in the mother and transmission to the infant. Potent antiretroviral therapy is now recommended for all HIV-infected pregnant women using the same criteria for non-pregnant individuals. If possible, combination antiretroviral regimens should include the use of zidovudine but not at the expense of long-term viral suppression. The use of elective Caesarean section should probably be reserved for women who fail to achieve viral suppression at the time of delivery or if indicated for obstetrical reasons. The practice of breastfeeding has been shown to diminish the long-term efficacy of perinatal antiretroviral therapy. All HIV-infected mothers should avoid breastfeeding the newborn if possible. This review summarizes major prospective and retrospective antiretroviral treatment studies in HIV-infected pregnant women. Pharmacokinetic information as it relates to pregnancy and adverse event profiles of antiretroviral agents are also discussed. The impact of recent advances in the management of HIV infection in pregnancy is discussed with regard to their feasibility in resource-poor countries.

Presence of human immunodeficiency virus (HIV) type 1, group M, non-B subtypes, Bronx, New York: a sentinel site for monitoring HIV genetic diversity in the United States.

In the United States, human immunodeficiency virus (HIV) type 1, group M, subtype B is the predominant subtype. A cross-sectional study of HIV-infected patients at the Bronx-Lebanon Hospital Center, Bronx, NY, between September 1997 and February 1998 identified 3 (1. 2%) of 252 persons infected with non-B subtypes: subtypes A and F, 1 each, and 1 potential recombinant subtype B(env)/F(prt). All 3 persons were born in the United States and tested positive for HIV antibodies between 1988 and 1997 while living in the Bronx. None reported travel to other countries, receipt of blood products, or drug injection. This study is among the first to indicate probable transmission of non-B HIV-1 subtypes in the United States. The occurrence of non-B HIV-1 subtypes in long-term US residents without a history of foreign travel may have implications for the evaluation and development of antiretroviral drugs, vaccines, and tests intended for use in the United States to diagnose HIV infection and screen blood.

Combination antiretroviral therapy in human immunodeficiency virus-infected pregnant women.

OBJECTIVE: To describe the safety, efficacy, and perinatal transmission rates of human immunodeficiency virus (HIV) with combination antiretroviral therapy in pregnancy. METHODS: Retrospective study of all HIV-infected pregnant women treated with combination antiretroviral therapy after September 1, 1996, and who delivered by September 1, 1998, at Bronx-Lebanon Hospital Center. RESULTS: Thirty women received combination therapy, 13 with protease inhibitor. Median baseline CD4 was 285 cells/mm3; 16 (53%) had AIDS, 20 (67%) were antiretroviral-experienced, and 11 (37%) were illicit substance users. Fourteen were receiving antiretroviral therapy (eight with protease inhibitor) during the first trimester. Combination therapy was prescribed for a median of 26 weeks during pregnancy. One third changed antiretroviral therapy, and nearly half (47%) were nonadherent. Twenty-four women had a successful viral load and/or CD4 response. The median (range) delivery gestation was 39 (32-42) weeks, and the median (range) birth weight was 2892 (1430-3863) g. Adverse outcomes included one stillbirth; one case of microcephaly; and five infants less than 2500 g, two of which were under 36 weeks' gestation. Median birth weight did not differ with maternal protease exposure. None of the 26 infants studied for at least 4 months had HIV infection. Associated maternal complications were four cases of pregnancy-induced hypertension, one of gestational diabetes, and one exacerbation of hepatitis C virus. CONCLUSION: Combination antiretroviral therapy in pregnancy was efficacious in reducing viral load, increasing CD4, and preventing vertical HIV transmission in women with advanced HIV disease, extensive antiretroviral experience, prior history of vertical transmission, and/or substance abuse. The findings are promising in this preliminary report that combination antiretroviral therapy may not be related to major infant toxicity, but further study is warranted.

Adherence to antiretroviral medications in an inner-city population.

Adherence to antiretroviral medications is essential for optimal treatment of HIV infection. We investigated nonadherence to antiretroviral medications in an inner-city population by using a confidential interview and a self-administered anonymous questionnaire. We estimated adherence on the day before and the month before the interview and asked reasons for nonadherence. Of 173 people who were taking antiretroviral medications, all participated in the confidential interview and 101 also completed the anonymous questionnaire. Results of the confidential interview and the anonymous questionnaire revealed rates of 6% and 28%, respectively, for nonadherence to any drug on the preceding day and of 11% and 39%, respectively, in the preceding month. The most common reasons for nonadherence in both methods were forgetfulness, inaccessibility of medications, and perceived or actual toxicity. On 12% of the anonymous questionnaires one reason for nonadherence was perceived or actual lack of drug efficacy: this reason was not given in any of the confidential interviews. Responses about the extent of nonadherence and the reasons for it may differ depending on the method of ascertainment. Interventions to improve adherence should focus on making medication dosages easier to remember, ensuring a continued supply of medications, and circumventing toxicities.

Serum IgE levels in patients with human immunodeficiency virus infection.

BACKGROUND: Increased serum IgE levels are associated with advanced HIV infection. The magnitude of the increase has varied greatly between studies which generally did not assess potential confounding factors. OBJECTIVE: To determine whether the increased serum IgE levels reported with HIV infection is affected by demographic or behavioral factors, we studied injection drug users, women, and minority ethnic and racial groups with HIV infection, for whom little data now exist. METHODS: A prospective cross-sectional study of ambulatory patients with or at risk for HIV infection was performed. We enrolled 83 injection drug users and 56 non-drug users seropositive for HIV and 43 seronegative at-risk individuals from an Infectious Diseases clinic and a longitudinal study of HIV infection in injection drug users in the Bronx, New York City. Fifteen HIV-seronegative non-atopic controls were also studied. Total serum IgE levels were measured by a solid phase fluorescent assay and lymphocyte phenotypes were measured by monoclonal antibodies. RESULTS: On multiple linear regression analysis, HIV infection (P=.01) and advanced HIV disease (P < or =.01) were independently associated with increased serum IgE levels, controlling for gender, race, age, and use of injection drugs. In both HIV-seronegative and seropositive individuals, female gender was independently associated with lower IgE levels (P < or = .001). We did not find an independent effect of race or injection drug use on IgE levels. CONCLUSIONS: Increased serum IgE levels were associated with HIV infection, the highest levels existing in those with advanced HIV disease. Women had lower IgE levels than men, independent of HIV status. Active or past drug use, race, and age were not found to be independently associated with serum IgE levels. Further studies are necessary to elucidate the mechanisms underlying the increased serum IgE levels seen with HIV infection and its associated immunodeficiency, and to substantiate and explore the decreased levels found in women.