Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir- than with efavirenz-based antiretroviral therapy.

BACKGROUND: There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub-Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG). METHODS: We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana, excluding those with pre-existing diabetes. We screened for GDM using a 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks' gestation or at the earliest prenatal visit for those presenting after 28 weeks. Logistic regression models were fitted to assess the association between maternal HIV infection and GDM. Subgroup analyses were performed among WLHIV to assess the association between maternal antiretroviral therapy (ART) in pregnancy [DTG vs. efavirenz (EFV) with tenofovir/emtricitabine] and GDM. RESULTS: Of 486 pregnant women, 66.5% were WLHIV, and they were older than women without HIV (median age 30 vs. 25 years, P < 0.01). Among WLHIV, 97.8% had an HIV-1 RNA level < 400 copies/mL at enrolment. Overall, 8.4% had GDM with similar rates between WLHIV and those without HIV (9.0% vs. 7.4%). The WLHIV receiving DTG-based ART had a 60% lower risk for GDM compared with those on EFV-based ART (adjusted odds ratio = 0.40, 95% CI: 0.18-0.92) after adjusting for confounders. CONCLUSIONS: Pregnant WLHIV on ART in Botswana were not at increased risk of GDM compared with women without HIV. Among WLHIV, the risk of GDM was lower with DTG- than with EFV-based ART. Further studies with larger cohorts are warranted to confirm these findings.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

Cost and cost-effectiveness of transitioning to universal initiation of lifelong antiretroviral therapy for all HIV-positive pregnant and breastfeeding women in Swaziland.

OBJECTIVES: To assess the costs and cost-effectiveness of transitioning from antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant and breastfeeding women in Swaziland. METHODS: We measured the total costs of prevention of mother-to-child HIV transmission (PMTCT) service delivery at public sector facilities with empirical cost data collected at three points in time: once under Option A and again twice after transition to the Option B+ approach. The cost per woman treated per month includes recurrent costs (personnel, overheads, medication and diagnostic tests) and capital costs (buildings, furniture, start-up costs and training). Cost-effectiveness was estimated from the health services perspective as the cost per woman retained in care through 6 months postpartum. This analysis is nested within a larger stepped-wedge evaluation, which demonstrated a 26% increase in maternal retention after the transition to Option B+. RESULTS: Across the five sites, the total cost for PMTCT during the study period (from August 2013 to October 2015, in 2015 US$) was $868,426 for Option B+ and $680 508 for Option A. The cost per woman treated per month was $183 for a woman on ART under Option B+, and $127 and $118 for a woman on ART and zidovudine (AZT), respectively, under Option A. The weighted average cost per woman treated on Option B+ was $826 compared to $525 under Option A. The main cost drivers were the start-up costs, additional training provided and staff time spent on PMTCT tasks for Option B+. The incremental cost-effectiveness ratio was estimated at $912 for every additional mother retained in care through six months postpartum. CONCLUSIONS: The cost and cost-effectiveness outcomes from this study indicate that there is a robust economic case for pursuing the Option B+ approach in Swaziland and similar settings such as South Africa. Furthermore, these costs can be used to aid decision making and budgeting, for similar settings transitioning to test and treat strategy.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

CONTEXT: HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. OBJECTIVE: We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. METHODS: As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. RESULTS: Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). CONCLUSION: Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes.

'There's no place like home': perceptions of home-based HIV testing in Lesotho.

HIV testing has the potential to reduce HIV transmission by identifying and counseling individuals with HIV, reducing risk behaviors, linking persons with HIV to care and earlier treatment, and reducing perinatal transmission. In Lesotho, a high HIV prevalence country in which a large proportion of the population has never tested for HIV, home-based testing (HBT) may be an important strategy to increase HIV testing. We identified factors influencing acceptability of HIV prevention strategies among a convenience sample of 200 pregnant or post-partum Basotho women and 30 Basotho men. We first conducted cross-sectional surveys, followed by key informant interviews with all 30 men and focus group discussions with a sub-set of 62 women. In total, 82% of women reported positive perceptions of HBT; women and men viewed HBT as a potential way to increase testing among men and saw the home as a comfortable, supportive environment for testing and counseling couples and families together. Potential barriers to HBT uptake included concerns about confidentiality, privacy, coercion to test, conflict within the family and fear of HIV/AIDS-associated stigma. Participants emphasized community mobilization and education as important elements of HBT.

Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe a family-focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother-to-child transmission (MTCT)-plus program in Abidjan, Côte d'Ivoire. PROGRAM: The MTCT-plus initiative aims to enroll HIV-infected pregnant and postpartum women in comprehensive HIV care and treatment for themselves and their families. MAIN OUTCOMES: Between August 2003 and August 2005, 605 HIV-infected pregnant or postpartum women and 582 HIV-exposed infants enrolled. Of their 568 male partners reported alive, 52% were aware of their wife's HIV status and 30% were tested for HIV; 53% of these tested partners were found to be HIV-infected and 78% enrolled into the program. Overall only 10% of the women enrolled together with their infected partner. On the other hand, the program involved half of the seronegative men who came for voluntary counselling and testing (VCT) in the care of their families. Of 1624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 10.8% were brought in for HIV testing, of whom 12.3% were found to be HIV-infected. LESSONS LEARNED AND CHALLENGES: The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges such as disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.

The Tingathe Surge: a multi-strategy approach to accelerate HIV case finding in Malawi.

SETTING: Nineteen health facilities in rural, southeastern Malawi. OBJECTIVE: To describe the implementation and results of a 6-week intervention to accelerate human immunodeficiency virus (HIV) case finding. DESIGN: Six HIV testing strategies were simultaneously implemented. Routinely collected data from Ministry of Health registers were used to determine the number of HIV tests performed and of new cases identified. The weekly averages of the total number of tests and new cases before and during the intervention were compared. Testing by age group and sex was described. The percentage yield of new cases was compared by testing strategy. RESULTS: Of 29 703 HIV tests conducted, 1106 (3.7%) were positive. Of the total number of persons tested, 69.5% were women and 75.5% were aged >15 years. The yield of positive test results was 3.5% among women, 4.3% among men, 4.4% among those aged >15 years and 1.5% among those aged ⩽15 years. The average weekly number of tests increased 106.7% from 3337 to 6896 (P = 0.002). The average weekly number of positive cases identified increased 51.9% from 158 to 240 (P = 0.017). The testing strategy with the highest yield resulted in a 6.0% yield; the lowest was 1.3%. The yield for all strategies, except one, was highest in adult men. CONCLUSION: A multi-strategy approach to HIV testing and counseling can be an effective means of accelerating HIV case finding.

Burden of tuberculosis in HIV-positive pregnant women in Cape Town, South Africa.

BACKGROUND: The burden of active tuberculosis (TB) in pregnancy compared with preconception and postpartum is unclear, particularly with universal antiretroviral therapy (ART) initiation in pregnancy. METHODS: We retrospectively compared active TB incidence in the 18 months preconception, during pregnancy and up to 6 months postpartum in human immunodeficiency virus (HIV) positive women attending antenatal care at a primary health care facility in Cape Town from 2013 to 2014. RESULTS: Among 1513 women (4116 person-years [py]), 1489 (98.4%) received lifelong ART in pregnancy, and 79 TB episodes were identified. Unadjusted TB incidence rates (IR) preconception, during pregnancy and postpartum were 2466 (95%CI 1863-3202), 1127 (95% CI 600-1928) and 1447 (95% CI 694-2661) per 100 000 py, respectively. Adjusting for age and CD4 count at first antenatal visit and ART status, TB risk was lower during pregnancy (incidence rate ratio [IRR] 0.17 vs. preconception, 95%CI 0.09-0.31) and increased slightly postpartum (IRR 1.31 vs. pregnancy, 95%CI 0.56-3.07). CONCLUSION: Among HIV-positive women in South Africa, the TB burden preconception, during pregnancy and postpartum was substantial. The risk of TB during pregnancy was lower than preconception, but increased slightly postpartum; this represents missed opportunities for diagnosis, prevention and control. Improved TB prevention strategies and integrated care for HIV-positive women and their children are needed.

Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.

Cutting the cost of South African antiretroviral therapy using newer, safer drugs.

Antiretrovirals are a significant cost driver for HIV programmes. Current first-line regimens have performed well in real-life programmes, but have a low barrier to virological resistance and still carry toxicity that limits adherence. New drug developments may mean that we have access to safer, more robust and cheaper regimens, but only if the appropriate clinical trials are conducted. We briefly discuss these trials, and demonstrate the large cost savings to the South African HIV programme if these are successful.

Mother-to-child discordance in HLA-G exon 2 is associated with a reduced risk of perinatal HIV-1 transmission.

Definitive genetic parameters correlating with mother-to-child transmission (MCT) of HIV have not been fully established. We screened for the potential correlation between HLA-G variants and MCT, in a cohort of mother-child pairs. Discordance in exon 2 of HLA-G was significantly more common among non-transmitting (93%) than transmitting mother-child pairs (40%). Our results suggest that mother-child pairs both carrying the identical mutation in HLA-G exon 2 may be at higher risk of MCT of HIV-1.

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

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

OBJECTIVES: 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. DESIGN: 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. METHODS: Non-parametric Kaplan-Meier method and parametric survival analysis. RESULTS: 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. CONCLUSIONS: 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.

Heterosexual behavior during pregnancy and perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the relationship between maternal heterosexual activity during pregnancy and perinatal transmission of HIV-1. DESIGN: A retrospective analysis of 175 New York City HIV-1-seropositive women enrolled during pregnancy or immediately post-partum from 1986 to 1994 in a prospective cohort study. METHODS: Frequency of heterosexual intercourse and condom use during pregnancy was determined from self-report measures. Unprotected intercourse was defined as follows: 'none', consistent condom use or abstinence; 'moderate', inconsistent condom use and fewer than 80 episodes of intercourse; and 'high', inconsistent condom use and 80 or more episodes. RESULTS: The rate of perinatal HIV-1 transmission was 9.1% (four out of 44) among women with no unprotected intercourse during pregnancy, 22.2% (20 out of 90) among those with moderate frequency, and 39.0% (16 out of 41) among those with high frequency (P < 0.01). The relative risk (RR) of perinatal transmission was higher among women with moderate [RR, 2.4; 95% confidence interval (Cl), 0.9-6.7] and high frequency of unprotected sexual intercourse (RR, 4.3; 95% Cl, 1.6-11.8) compared with women with no unprotected sexual intercourse. When potential covariates (maternal injecting drug use, CD4 lymphocyte count, AIDS, zidovudine use, pelvic inflammatory disease or sexually transmitted disease during pregnancy, delivery mode, and extreme prematurity) were included in a logistic regression model (n = 128), the rate of perinatal transmission remained significantly higher among women with any unprotected sexual intercourse during pregnancy. CONCLUSIONS: Data suggest that unprotected sexual intercourse during pregnancy influences perinatal HIV-1 transmission.

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

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.

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Neurological correlates of fetal cocaine exposure: transient hypertonia of infancy and early childhood.

OBJECTIVE: To assess whether prenatal cocaine exposure has any long-term effects on neurodevelopment. DESIGN: A prospective cohort study with examiners blind to drug exposure and human immunodeficiency virus (HIV) status. SUBJECTS: Of 144 high-risk infants enrolled in a perinatal HIV neurodevelopmental study, 119 (83%) infants with both neurological and urine toxicology measures were followed up to age 24 months. METHODS: Neurological and developmental assessments were analyzed at 6-month intervals grouped according to the presence of cocaine in urine toxicology: 51 infants were cocaine-positive. Adjusted odds ratios (ORs) and 95% confidence interval (CI) were obtained by logistic regression equations that adjusted for perinatal variables, including measures of fetal growth, gestation, HIV status, and infant toxicology results. SETTING: Harlem Hospital Center from 1988 to 1992. RESULTS: At age 6 months, 21 of 51 (41%) cocaine-positive children exhibited hypertonia of any type (hypertonic tetraparesis, hypertonic diparesis, and hypertonic hemiparesis) compared with 17 of 68 (25%) cocaine-negative infants (OR = 2.1, CI = 1.0-4.6). Cocaine-positive infants were four times more likely to show hypertonic tetraparesis (HTP) than cocaine-negative infants (OR = 4.0; CI = 1.5-10.8). The association remained significant in multivariate analyses. Hypertonia, consistent with cerebral palsy, diminished over time in both groups. In 97% of affected infants hypertonia resolved by 24 months. Arm hypertonia abated first; leg hypertonia remained in some children up to age 18 months. No differences in development scores between cocaine-positive and cocaine-negative were noted at any age interval. However, among cocaine-positive infants those with early HTP showed significantly lower mean developmental scores at 6 and 12 month compared to infants without HTP. CONCLUSION: Cocaine positivity urine toxicology at birth is associated with hypertonia during infancy. Such cocaine-induced effects are usually symmetrical, transient, and the majority of exposed children outgrow hypertonia by 24 months of life. Among cocaine-positive infants, HTP may be a marker for later developmental impairments.