Time trends for HIV-1 antiretroviral resistance among antiretroviral-experienced and naive pregnant women in New York City during 1991 to early 2001.

Time trends in the prevalence of drug resistance to antiretroviral therapy (ART) in pregnant women have not been studied. Treatment and prophylactic efficacy could be compromised by drug-resistant HIV strains. We conducted a repeated cross-sectional study of antiretroviral resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) and of major mutations to protease inhibitors (PIs) in virus isolates from 300 HIV-infected pregnant women in New York City from 1991 to early 2001.

Antiretroviral resistance in viral isolates from HIV-1-transmitting mothers and their infants.

Objective: To characterize concordance of resistance mutations to antiretroviral drugs (ART) in mother-infant pairs.

Design: Case series of HIV-transmitting mothers and infants in the Women and Infants Transmission Study, where delivery occurred between April 1994 and December 1999.

Methods: Reverse transcriptase and protease genes were sequenced in stored viral isolates from 32 mother-infant pairs.

Pharmacokinetics of didanosine and drug resistance mutations in infants exposed to zidovudine during gestation or postnatally and treated with didanosine or zidovudine in the first three months of life.

Background: There are limited numbers of drugs that are available in formulations that are appropriate for neonates and few studies assessing resistance among infants born to human immunodeficiency virus (HIV)-infected women.

Methods: Pharmacokinetics and tolerance of didanosine (ddI) were determined for infants < or =120 days of age. Infants received at least 24 hours of zidovudine (ZDV) treatment, followed by a single ddI dose and pharmacokinetic sampling.

Gag-p6 Tsg101 binding site duplications in maternal-infant HIV infection.

Prevalence and patterns of HIV p6 duplications in HIV-1 mother-to-baby transmission are examined. Resistance genotyping was performed in a multisite U.S.

Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy.

Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use.

Hepatitis C virus coinfection and HIV load, CD4+ cell percentage, and clinical progression to AIDS or death among HIV-infected women: Women and Infants Transmission Study.

Background: Despite previous study, it remains unclear whether hepatitis C virus (HCV) coinfection affects the progression of human immunodeficiency virus (HIV) type 1 infection. The Women and Infants Transmission Study provided an opportunity to assess this issue.

Methods: Longitudinal data on 652 HIV-1-infected women enrolled in the study before the availability of highly active antiretroviral therapy (HAART; 1989-1995) were analyzed.

Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: the women and infants transmission study.

Objective: We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV) type 1-infected women enrolled in the Women and Infants Transmission Study (WITS) during an 11-year period (1990-2001).

Design And Methods: As part of WITS, evaluations were performed at birth and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age. Growth, hospitalization and the incidence of clinical disease were assessed regularly.

Effect of hard-drug use on CD4 cell percentage, HIV RNA level, and progression to AIDS-defining class C events among HIV-infected women.

In vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit ("hard")--drug use.

Mother-to-child transmission of HIV-1: strong association with certain maternal HLA-B alleles independent of viral load implicates innate immune mechanisms.

The transmission of HIV-1 from mother to child during pregnancy is unlike other types of HIV-1 transmission because the child shares major histocompatibility complex (MHC) genes with the mother during a time while the mother is induced to tolerate the paternally derived fetal MHC molecules, in part through natural killer (NK) recognition of MHC polymorphisms. The relevance of these immune mechanisms to HIV-1 transmission was assessed by determining the HLA-B alleles of mother and infant. Almost half (48%) of mothers who transmitted with low viral loads had HLA-B*1302, B*3501, B*3503, B*4402, or B*5001 alleles, compared with 8% of nontransmitting mothers (P=0.

Immune parameters and morbidity in hard drug and human immunodeficiency virus-exposed but uninfected infants.

Objective: To examine the association of maternal hard drug use (injection drugs, cocaine, and opiates) on lymphocyte subsets and clinical morbidity in uninfected infants who are born to human immunodeficiency virus-infected mothers who were enrolled in the Women and Infants Transmission Study (1990-2000).

Methods: Maternal hard drug use was identified by self-report and/or urine toxicology. Infant evaluations occurred at birth and at 1, 2, 4, 6, 9, 12, 18, and 24 months of age.

Pharmacokinetics of saquinavir plus low-dose ritonavir in human immunodeficiency virus-infected pregnant women.

The physiologic changes that occur during pregnancy make it difficult to predict antiretroviral pharmacokinetics (PKs), but few data exist on the PKs of protease inhibitors in human immunodeficiency virus (HIV)-infected pregnant women. The objective of the present study was to determine the PKs of ritonavir (RTV)-enhanced saquinavir (SQV) in HIV-infected pregnant women by an area under the curve (AUC)-targeted approach. A phase I, formal PK evaluation was conducted with HIV-infected pregnant woman during gestation, during labor and delivery, and at 6 weeks postpartum.

Zidovudine resistance phenotype and risk of perinatal HIV-1 transmission in zidovudine monotherapy-treated mothers with moderately advanced disease.

The association of phenotypic zidovudine resistance with perinatal transmission was evaluated in 74 zidovudine-treated mothers enrolled in the Women and Infants Transmission Study through September 1994. Women in the sample had moderately advanced disease, with a median CD4+ cell count of 271/microL and a median plasma HIV-1 RNA level of 39,811 copies/mL. Factors independently associated with zidovudine resistance at delivery (50% inhibitory concentration [IC50], >/=0.

Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.

Objectives: To define the tolerated dose of recombinant interleukin-2 (rIL-2) in HIV-infected children (part A), and to determine the safety and immunologic effects of the tolerated rIL-2 dose in a cohort of HIV-infected children (part B).

Design: Open-label, dose-escalation.

Setting: Multiple center study.

The relationship of pregnancy to human immunodeficiency virus disease progression.

Objective: This study was undertaken to determine the effect of pregnancy on progression of human immunodeficiency virus (HIV) disease.

Study Design: We compared the immunologic, clinical, and virologic courses of 953 women who had no additional pregnancy after their index pregnancy, with the courses of 329 women who had a second pregnancy subsequent to their index pregnancy. Baseline variables included use of antiretroviral therapy, and CD4 and HIV RNA values.

Multicenter evaluation of use of dried blood and plasma spot specimens in quantitative assays for human immunodeficiency virus RNA: measurement, precision, and RNA stability.

Eleven laboratories evaluated the use of dried blood and plasma spots for quantitation of human immunodeficiency virus (HIV) RNA by two commercially available RNA assays, the Roche Amplicor HIV-1 Monitor and the bioMerieux NucliSens HIV-1 QT assays. The recovery of HIV RNA was linear over a dynamic range extending from 4,000 to 500,000 HIV type 1 RNA copies/ml. The Monitor assay appeared to have a broader dynamic range and seemed more sensitive at lower concentrations.

Risk factors for Kaposi's sarcoma-associated herpesvirus infection among HIV-1-infected pregnant women in the USA.

Objectives: We sought to identify risk factors for infection with the Kaposi's Sarcoma-associated herpesvirus (KSHV) among pregnant women and to examine a reported association of KSHV with injecting drug use (IDU) and hepatitis C virus (HCV) infection.

Design: Cross-sectional evaluation of questionnaire data and KSHV and HCV seroprevalence in the Women and Infants Transmission Study.

Methods: In sera collected from HIV-1-infected pregnant women (n = 887) and, at age 12 months, their offspring (n = 900) at six sites in the USA and Puerto Rico, KSHV and HCV antibodies were detected with sensitive and specific enzyme immunoassays.

Evaluation of coxsackievirus infection in children with human immunodeficiency virus type 1-associated cardiomyopathy.

In a matched case-control study of the association between coxsackieviruses and cardiac impairment, 24 human immunodeficiency virus (HIV) type 1-infected children with cardiac impairment were compared with 24 HIV-1-infected control subjects. Serologic evidence of coxsackievirus infection was present in all children, with no significant difference in geometric mean antibody titers between case patients and control subjects. Conditional logistic regression to test for an association between coxsackievirus antibody titer and the presence or absence of cardiac impairment, by any indicator, showed an odds ratio of 1.

Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV transmission.

A case-control design study was used to investigate the association of maternal HIV-1 phenotype in MT-2 cells at or near the time of delivery with perinatal transmission of HIV-1, controlling for maternal CD4 percentage and duration of rupture of membranes, in 48 transmitting and 96 non-transmitting HIV-1-infected mothers who gave birth between 1990 and 1995. The non-syncytium-inducing (NSI) phenotype was more commonly seen in transmitting mothers compared with non-transmitting mothers (90% vs. 75%, p =.

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.

Addenbrooke's reunion.

It will be ten years this year since the September 1975 set qualified at Addenbrooke,s Hospital, Cambridge.