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Objective: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus., Design: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405)., Methods: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates., Results: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04)., Conclusion: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.

Purpose of Review: Because of widespread availability of highly active antiretroviral therapy in the developed world, a large proportion of children with perinatally acquired HIV have survived to adolescence and young adulthood. Although their survival is remarkable, many now experience the long-term effects of HIV infection and its treatment. Further, as these youths have entered adolescence, more is known about the impact of normative developmental transitions on health maintenance behaviors., Recent Findings: Although perinatally infected adolescents are healthier than they were a decade or more ago, they are significantly experienced with antiretroviral therapy, with increased virological resistance and other consequences of extended antiretroviral use. Three behavioral health challenges have been documented in the first cohort of long-term survivors: decreased medication adherence, sexual debut and accompanying pregnancy and transmission risk, and mental health problems. These issues are consistent with a developmental press for autonomy, mature sexual relationships and future planning, but must be carefully managed to preserve health., Summary: Adolescents with perinatally acquired HIV require coordinated multidisciplinary support services - including adherence support, reproductive health counseling addressing both pregnancy planning and disease transmission, and mental health and educational/vocational planning - so that they can fully benefit from treatment advances., ((C) 2011 Lippincott Williams & Wilkins, Inc.)

The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine rapid HIV testing in labor and delivery (L&D) for women with undocumented HIV status using an opt-out approach. Identifying factors associated with declining a rapid HIV test in L&D will be helpful in developing strategies to improve rapid HIV testing uptake. Data from the Mother-Infant Rapid Intervention at Delivery study were analyzed. Women ≥24 weeks gestation, in labor, with undocumented HIV status were offered rapid HIV testing using informed consent. Women who declined rapid HIV testing (decliners) but agreed to be interviewed were compared to women who accepted testing (acceptors). 102 decliners and 478 acceptors met inclusion criteria for analysis. Decliners of rapid HIV testing were more likely to have had prenatal care (PNC), after adjusting for age, Hispanic ethnicity, high-school education and city of enrollment (adjusted OR 2.4, 95% CI 1.06-5.58). Having had PNC was collinear with prior HIV education and previous offer of an HIV test during the current pregnancy, so these factors were not part of the model. During PNC, standard informed consent may involve discussions that negatively affect later uptake of testing in L&D. Therefore an opt-out approach to testing may improve testing rates. Furthermore, decliners may have felt that testing in L&D was redundant because of previous testing during PNC; however, if previous testing occurred, this was undocumented at L&D. Documentation and timely communication of HIV status is critical to provide appropriate HIV prophylaxis.

Background: Involvement of the thymus during human immunodeficiency virus (HIV) infection may impair production of naive lymphocytes leading to more rapid depletion, but the characteristics of primary strains in the thymus are not well studied because of the unavailability of tissue in living individuals., Methods: We studied the characteristics of HIV type 1 (HIV-1) in a 5-year old perinatally infected child with thymitis and compared the genomic sequences of the HIV-1 C2-V5 region of the env gene in the thymic tissue and peripheral blood., Results: The thymus harbored predominantly viral sequences close to the founder HIV-1 variant that circulated in the blood at 2 and 3 months of age, whereas the peripheral blood virus at 5 years of age had evolved extensively. Viral sequences from circulating CD8(+) T cells at 5 years of age phylogenetically clustered with those from the thymic tissue., Conclusions: These results indicate the existence of a distinct thymic viral reservoir and suggest that circulating CD8(+) T cells were infected in the thymus, presumably at the CD4(+)CD8(+) thymocyte stage. They also demonstrate that not all thymic HIV infections will necessarily lead to severe thymic dysfunction. The characteristics of the virus strain seeding the thymus may dictate the rate of disease progression.

The objective of the study was to evaluate the feasibility, acceptability, and accuracy of rapid human immunodeficiency virus (HIV) testing during labor. The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study was a prospective, multicenter study that offered voluntary, rapid HIV testing to women with undocumented HIV status at 17 hospitals in 6 cities. Of 12,481 eligible women, 74% were approached for participation and 85.5% of those approached accepted rapid HIV testing. Among 7753 women tested, MIRIAD identified 52 (0.7%) HIV-infected women. The time between obtaining the blood sample for the rapid test and reporting the results to the health care provider was shorter for hospitals utilizing point-of-care testing than in hospitals utilizing laboratory-based testing (30 minutes vs 68 minutes; P < .0001), and point-of-care testing strategies were 14 times more likely to have a short turnaround as laboratory testing strategies. Routine rapid testing during labor provides a feasible, acceptable, and accurate way to identify HIV-infected women before delivery.

Recently, we developed an immunoglobulin G (IgG)-capture BED-enzyme immunoassay (BED-CEIA) to identify recent HIV-1 infections. We estimated HIV-1 incidence among inner-city pregnant women in Atlanta, Georgia (1991-1998) using this assay. The annual cumulative incidence was estimated at 2.4/1000 (95% CI = 2.0-2.9). Incidence declined from 3.1/1000 in 1991-1994 to 1.4/1000 in 1995-1998 (risk ratio = 2.3, 95% CI = 1.5-3.4). Women with recent HIV-1 infection more often reported a previous negative antibody test (p = 0.018) and sexual relations with men other than the father during the past year (p = 0.046). Fewer seroconverters in 1995-1998 used crack cocaine than in the earlier time period. A high but declining HIV-1 incidence was found among inner-city pregnant women in Atlanta.

Context: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis., Objectives: To determine the feasibility and acceptance of rapid HIV testing among women in labor and to assess rapid HIV assay performance., Design, Setting, and Patients: The Mother-Infant Rapid Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and voluntary rapid HIV testing for women in labor at 16 US hospitals from November 16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood was used., Main Outcome Measures: Acceptance of HIV testing; sensitivity, specificity, and predictive value of the rapid test; time from blood collection to patient notification of results., Results: There were 91,707 visits to the labor and delivery units in the study, 7381 of which were by eligible women without documentation of HIV testing. Of these, 5744 (78%) women were approached for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test were 100% and 99.9%, respectively; positive predictive value was 90% compared with 76% for enzyme immunoassay (EIA). Factors independently associated with higher test acceptance included younger age, being black or Hispanic, gestational age less than 32 weeks, and having had no prenatal care. Lower acceptance was associated with being admitted between 4 pm and midnight, particularly on Friday nights, but this may be explained in part by fewer available personnel. Median time from blood collection to patient notification of result was 66 minutes (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001)., Conclusions: Rapid HIV testing is feasible and delivers accurate and timely test results for women in labor. It provides HIV-positive women prompt access to intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal HIV transmission, and may be particularly applicable to higher-risk populations.

Objective: To determine the relationship of maternal health factors and infant antiretroviral treatment to the risk of pediatric disease progression to AIDS or death by 24 months of age., Design: Prospective perinatal HIV-1 transmission and pediatric natural history study., Setting: Urban medical centers in four cities in the USA., Participants: A total of 2656 pregnant and postpartum HIV-infected women enrolled in the Perinatal AIDS Collaborative Transmission Study (PACTS) and 360 children determined to be HIV-infected., Main Outcome Measures: Pediatric AIDS or death by 24 months of age., Results: Children born to mothers with class C disease, CD4 cell count < 200 x 106/l, or HIV-1 RNA viral load > 100 000 copies/ml progressed more rapidly than children born to mothers with less advanced disease. In a multivariate analysis, there was an increased risk of progression if mothers had Class C disease [relative risk (RR), 1.7; 95% confidence interval (CI), 1.0-2.7] or HIV-1 RNA > 100 000 copies/ml (RR, 2.4; 95% CI, 1.2-4.6) controlling for child antiretroviral therapy and year of birth. Earlier years of birth significantly increased the likelihood of rapid progression (P = 0.01) in this multivariate model. Children who received combination antiretroviral therapies with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor were significantly less likely to progress compared with those receiving no therapy (P = 0.03)., Conclusions: HIV-1-infected infants born to women with advanced HIV-1 disease were at increased risk for rapid disease progression. More recent birth year and early treatment with potent antiretroviral therapy significantly diminished the likelihood of developing AIDS or dying during early childhood.

Quantitative HIV RNA testing was used for diagnosis in 156 HIV-exposed non-breast-fed infants at less than 6 months of age (54 infected, 102 uninfected) enrolled in the Perinatal AIDS Collaborative Transmission Study. Sensitivity was 29% in the first week, 79% at 8 to 28 days of age, and >90% at 29 days of age and thereafter; specificity was 100% in all periods, except at 29 to 60 days of age, when specificity was 93%. Neither sensitivity nor specificity was significantly affected by maternal or infant zidovudine (ZDV) treatment, even though infant viral loads were lower during the first 6 weeks in infants who received perinatal ZDV prophylaxis ( p=.005). Paired analysis of DNA and RNA measurements revealed no advantage for either test. Quantitative RNA testing can be used for diagnosis in HIV-exposed infants, recognizing the chance for a false-positive test result. It may be most useful as a confirmatory test in infants with another positive diagnostic test result.

To assess the impact of antiretroviral resistance on perinatal transmission prevention efforts, human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing was done for 220 HIV-1-infected, zidovudine (AZT)-exposed pregnant women and 24 of their infected infants. The women were prospectively enrolled in 4 US cities in 1991-1997. Phylogenetic and sequencing analyses revealed 5 women with non-clade B infections traced to western African origins. AZT-associated mutations were detected in 17.3% of pregnant women, whereas genotypic resistance to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors was infrequent. No significant association was detected between perinatal transmission and the presence of either AZT or nucleoside reverse-transcriptase inhibitor resistance-associated mutations. AZT resistance mutations were detected in 2 (8.3%) neonatal samples, but the mutation pattern was not identical to the mother's. Although no effect of viral resistance on mother-infant transmission was demonstrated, the advent of more-potent drug classes and the potential for the rapid emergence of resistance warrant prospective surveillance.

Objective: HIV infections in children are characterized by high viral load and, in some perinatally infected newborns, delayed appearance of viral markers. Both phenomena may be related to different levels of immune activation affecting viral replication. This study was designed to investigate the relationship between immune activation and viral replication in pediatric HIV infection, and the role of pre-existent immune activation in facilitating HIV transmission to the fetus/newborn., Design: Plasma levels of soluble L-selectin (s-LS), an immune activation marker, were determined in 100 infants with perinatally transmitted HIV infection, compared with 106 age-matched HIV-exposed uninfected controls. Included in the analysis were samples from 31 HIV-infected (10 PCR+ and 21 PCR-) and 35 uninfected newborns aged < 2 days., Methods: To determine s-LS levels, a solid phase ELISA was performed on plasma samples of patients and controls., Results: s-LS levels in uninfected children were higher than those in normal adults. HIV-infected patients had more rapidly increasing values in the first 6 months of life compared with uninfected infants. Plasma s-LS levels correlated with HIV viral loads (r, 0.50). Among newborns in the first 2 days of life, s-LS levels were lowest in those with negative PCR tests, compared with PCR-positive or uninfected infants., Conclusions: These results suggest that higher immune activation in children contributes to higher viral loads, and that the level of pre-existent immune activation may have a role in determining which infants have detectable virus in peripheral blood at birth.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

Objectives: 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., Design: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities., Methods: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics., Results: 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., Conclusions: 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.