Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Adherence to tablet and liquid formulations of antiretroviral medication for paediatric HIV treatment at an urban clinic in Uganda.

BACKGROUND: Major obstacles remain in scaling up paediatric HIV treatment, including limited paediatric anti-retroviral drug options for resource-limited settings, challenges with adherence to liquid formulations and treatment fatigue with lifelong therapy. AIM: To determine levels of adherence to HAART in HIV-infected children at 12, 24, 36 and 48 weeks of follow-up and to compare adherence levels before and after switching from syrup to fixed-dose combination (FDC)-tablet anti-retroviral formulations. METHODS: HIV-infected children aged between 6 months and 12 years were initiated on anti-retroviral therapy at Makerere University-Johns Hopkins University Care Clinic, Kampala. Good adherence to HAART was defined as taking ≥95% of prescribed medications. Adherence levels were measured using pharmacy refill data, quarterly unannounced home-visit pill counts and caregiver self-reports. Data were analysed using STATA(®) version 10.0. RESULTS: A total of 129 HIV-infected children were initiated on HAART with 14.7% on syrups and 85.3% on tablet formulations at enrollment. According to caregiver self-reporting, 99.2%, 100%, 100% and 99.2% achieved ≥95% adherence at 12, 24, 36 and 48 weeks, respectively. Using pharmacy refill data, the proportions were 89.9%, 95.4%, 93.8% and 93.0% and for unannounced home visits were 89.8%, 92.4%, 88.9% and 86.2%, respectively. Median adherence to syrup formulations (97%, IQR 93-98) was significantly lower than for tablets (100%, IQR 97-100, p = 0.012, n = 28) using pharmacy refill data. Viral suppression correlated with home visit and pharmacy refill adherence data. CONCLUSION: The majority of children initiating HAART had good adherence when estimated by caregiver self-report and pharmacy refill data but lower adherence when measured by home-visit pill counts. Adherence to tablet formulation of HAART was significantly better than syrup formulation. Medication formulation did not significantly affect viral suppression.

Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission.

OBJECTIVE: A recent trial in Uganda demonstrated that a simple, inexpensive regimen of nevirapine (NVP) prophylaxis can dramatically reduce HIV-1 vertical transmission risk. In this regimen, women receive a single dose of NVP at the onset of labor and infants receive a single dose of NVP within 72 h of birth. The objective of this study was to determine whether HIV-1 variants with NVP resistance mutations were selected in Ugandan women who received this regimen in the Phase I/II trial HIVNET 006. METHODS: Reverse transcriptase (RT) sequences from plasma HIV-1 were analyzed from 15 women 6 weeks after NVP dosing. RT sequences from plasma collected prior to NVP dosing were also analyzed. RESULTS: The K103N NVP resistance mutation was detected 6 weeks after NVP administration in three (20%) out of 15 women (95% confidence interval, 0-40%). Pre-dose samples were available from two of the three women; both pre-dose samples lacked the mutation. Other NVP resistance mutations were absent from all 15 women. Women with the K103N mutation had a longer median NVP elimination half-life, decreased median oral clearance, and increased median area under the concentration time curve than those without the mutation. An evaluable sample was obtained from one of these three women 33 months after delivery; the K103N mutation was not detected in that sample. CONCLUSIONS: This preliminary study demonstrates that HIV-1 with the RT K103N mutation can be detected in some Ugandan women following a single dose of NVP. This suggests that non-nucleoside RT inhibitor resistance may be selected in some people by single dose NVP prophylaxis. Pharmacokinetic data suggested that a more prolonged exposure to NVP after dosing may favor selection of NVP-resistant HIV-1.

HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group.

OBJECTIVES: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. METHODS: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. RESULTS: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P= 0.0001) and higher plasma HIV-1 RNA (P=0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P=0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P= 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P=0.009] were independently associated with transmission in multivariate analysis. CONCLUSION: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy.

Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission.

OBJECTIVE: To evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission. DESIGN: Multicenter prospective cohort study. SETTING: Obstetric and pediatric clinics in five cities in the United States. PARTICIPANTS: Five hundred and thirty HIV-infected pregnant women and their infants. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission. RESULTS: Forty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h. CONCLUSIONS: On the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission.

The contribution of assay variation and biological variation to the total variability of plasma HIV-1 RNA measurements. The Women Infant Transmission Study Clinics. Virology Quality Assurance Program.

OBJECTIVES: To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations. DESIGN: A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program. METHODS: Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation. RESULTS: The total variation (standard deviation) from a random effects model was 0.26 log10 RNA copies/ml. The estimated interassay variation was 0.08 log10 and intra-assay variation was 0.12 log10 RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal. CONCLUSION: Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained.

A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006).

OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. DESIGN: An open label phase I/II study. SETTING: Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. OUTCOMES: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. RESULTS: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team.

OBJECTIVE: To evaluate independent contributions of maternal factors to adverse pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy (ART). DESIGN: Risk factors for preterm birth (< 37 weeks gestation), low birth weight (LBW) (< 2500 g), and intrauterine growth retardation (IUGR) (birth weight < 10th percentile for gestational age) examined in 497 HIV-infected pregnant women enrolled in PACTG 185, a perinatal clinical trial. METHODS: HIV RNA copy number, culture titer, and CD4 lymphocyte counts were measured during pregnancy. Information collected included antenatal use of cigarettes, alcohol, illicit drugs; ART; obstetric history and complications. RESULTS: Eighty-six percent were minority race/ethnicity; 86% received antenatal monotherapy, predominantly zidovudine (ZDV), and 14% received combination antiretrovirals. Preterm birth occurred in 17%, LBW in 13%, IUGR in 6%. Risk of preterm birth was independently associated with prior preterm birth [odds ratio (OR) 3.34; P < 0.001], multiple gestation (OR, 6.02; P = 0.011), antenatal alcohol use (OR, 1.91; P = 0.038), and antenatal diagnosis of genital herpes (OR, 0.24; P = 0.022) or pre-eclampsia (OR, 6.36; P = 0.025). LBW was associated with antenatal diagnosis of genital herpes (OR, 0.08; P = 0.014) and pre-eclampsia (OR, 5.25; P = 0.049), and baseline HIV culture titer (OR, 1.41; P = 0.037). IUGR was associated with multiple gestation (OR, 8.20; P = 0.010), antenatal cigarette use (OR, 3.60; P = 0.008), and pre-eclampsia (OR, 12.90; P = 0.007). Maternal immune status and HIV RNA copy number were not associated with APO. CONCLUSIONS: Risk factors for APO in antiretroviral treated HIV-infected women are similar to those reported for uninfected women. These data suggest that provision of prenatal care and ART may reduce APO.

Geographic mobility and children's emotional/behavioral adjustment and school functioning.

OBJECTIVE: To evaluate the relationship of geographic mobility to children's emotional/behavioral adjustment and school functioning. DESIGN: Analysis of data from the 1988 National Health Interview Survey of Child Health in which multistage probability sampling was used to obtain data for nationally representative estimates of health and demographic characteristics of US children. PARTICIPANTS: 10,362 US school-age children and their families. MEASUREMENTS: The 1988 National Health Interview Survey of Child Health includes data on health and demographic characteristics, emotional/behavioral variables, school functioning, and geographic mobility for 10,362 US school-age children. This study examined the relationship of children's geographic mobility to children's reported emotional problems, use of psychological help, scores on a Behavior Problem Index, repeating a grade in school, and being suspended or expelled from school. RESULTS: Twenty-four percent of children have never moved, 35% of children have moved once or twice, and 39% of children aged 6 to 17 years have moved three or more times in their lifetime. Using multiple logistic regression to control for important demographic variables, children who moved three or more times were 2.3 times more likely to have received psychological help, 1.7 times more likely to have repeated a grade, and 1.9 times more likely to have been suspended or expelled from school compared with children who had never moved. Multiple regression was also used to analyze the impact of mobility in relation to scores on the Behavior Problem Index. Children who moved three or more times were 1.6 times more likely to be in the top tenth percentile of scores on the Behavior Problem Index compared with children who had never moved. CONCLUSIONS: Children who move three or more times are at increased risk for emotional/behavioral and school problems. Thus, pediatricians, other health professionals, and educators should be alert to the potential educational and psychological problems among children from highly mobile families.

School functioning of US children with asthma.

Data from the 1988 US National Health Interview Survey on Child Health, a nationally representative cross-sectional survey, were used to determine national estimates of school outcomes (grade failure, learning disabilities, and suspension/expulsion) and mean number of absences for children with asthma (CWA) compared to well children without current health conditions. Families indicated that 536 (4.9%) of the 10,362 survey children in grades 1 through 12 had had asthma in the previous 12 months. Families reported 18% of CWA vs 15% of well children had grade failure, 9% of CWA vs 5% of well children had learning disabilities, and 5% of CWA vs 6% of well children had been expelled or suspended. Children with asthma averaged 7.6 school days absent compared with 2.5 days for the well group. Multiple logistic regression was used to compare the odds of grade failure, learning disabilities, and suspension/expulsion among CWA and well children, overall and stratified by income. Similar methods were used to assess the role of health status among asthmatic children. After adjustment for demographic factors, CWA had similar risks of grade failure and suspension/expulsion, but 1.7 times the risk of learning disability compared with well children. Also, among families with incomes below $20,000, CWA had twice the odds of grade failure compared with well children. For asthmatic children, reported health status was an important predictor of learning disability. Ten percent of CWA were reported to be in fair-poor health. After adjustment for demographic factors, those in fair-poor health were twice as likely to have a reported learning disability compared with those in good-excellent health.(ABSTRACT TRUNCATED AT 250 WORDS)

Families on the move and children's health care.

OBJECTIVE: To evaluate the relationship of family moves to children's health care use. DESIGN: Analyses of data from the 1988 National Health Interview Survey of Child Health (NHIS-CH). This survey uses a multisite probability cluster technique to achieve nationally representative estimates of health and demographic characteristics of the US civilian population. PARTICIPANTS: 17,110 US children and their families who took part in the 1988 NHIS-CH. MEASUREMENTS: The 1988 NHIS-CH collected health and demographic data including family mobility information on 17,110 US children and their families. This study analyzed the relationship of number of family moves to reporting a regular site for preventive pediatric health care services, a regular site for pediatric sick care, and routine use of emergency departments when a child was sick. RESULTS: Overall, 8% of US children were reported to lack a regular site for preventive care services, 7% a site for sick care, and 3% routinely used an emergency department for sick care. However, 14% of children who had moved three or more times lacked a regular site for preventive care and 10% lacked a regular site for sick care, compared to only 3% of children who had never moved. Children who had moved more than twice were three times as likely to lack a regular site for preventive or sick care and 1.6 times as likely to use an emergency department for sick care, as were children who had never moved. CONCLUSIONS: Families with increased mobility are more likely to lack a regular site for both preventive and sick care and to use emergency departments when their children become ill.

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children. AIDS Clinical Trials Group Protocol 152 Study Team.

BACKGROUND: A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. METHODS: Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if < 30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to < 12 months, 12 to < 30 months, 30 months to 6 years and > or = 6 years). RESULTS: Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. CONCLUSIONS: These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children < 30 months of age demonstrates that treatment strategies should be developed for earlier intervention.

The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women. Women and Infants Transmission Study Group.

BACKGROUND: Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. METHODS: The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at approximately 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. RESULTS: Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 microg/ml) than among uninfected children (2.70 microg/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P > or = 0.48). The proportion of children with antibody concentrations > or = 1.0 microg/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P=0.81). CONCLUSIONS: These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued.

Prevention of perinatal HIV infection. What do we know? Where should future research go?

Major progress has been made in reduction of perinatal HIV transmission in the United States and Europe following the PACTG 076 results using zidovudine (ZDV) for prevention of mother-to-infant HIV transmission. Internationally in the past two years, short-course antiretroviral trials have shown efficacy for both antenatal or intrapartum and postnatal interventions. Trials in Bankok, Thailand, and Cote d'Ivoire demonstrated that antenatal ZDV started at 36 weeks could reduce transmission by 50% among non-breastfeeding women and about 37% among breastfeeding women. Uganda trial results with one dose of nevirapine given to the mother at the onset of labor and to the newborn resulted in a 47% reduction in transmission when compared to a regimen of ZDV given intrapartum and for 1 week to the newborn. These recent international research findings provide evidence that both short-course antenatal/intrapartum and intrapartum/neonatal prophylaxis can effectively reduce perinatal HIV transmission in resource-poor settings. In order to avert the 1600 new infant HIV infections occurring daily, the world community must act to rapidly implement these international perinatal trial results.

Lack of evidence of mitochondrial dysfunction in the offspring of HIV-infected women. Retrospective review of perinatal exposure to antiretroviral drugs in the Perinatal AIDS Collaborative Transmission Study.

A recent report suggesting mitochondrial dysfunction among eight HIV-exposed but uninfected children exposed perinatally to nucleoside reverse transcriptase inhibitors (NRTIs) prompted a review within the Perinatal AIDS Collaborative Transmission Study (PACTS). A standardized retrospective review was conducted of 118 deaths at < 5 years. Deaths were classified as unrelated to mitochondrial dysfunction (Class 1), unlikely related (Class 2), possibly related (Class 3), or likely related or proven (Class 4). Among 35 deaths recorded in HIV-uninfected or indeterminate children, none were classified in either Class 2, 3, or 4. We also reviewed signs or symptoms consistent with possible mitochondrial dysfunction among 1,954 living uninfected children. Only one child was in Class 3 and two siblings were in Class 2; none had perinatal antiretroviral drug exposure. We found no evidence indicating that uninfected infants exposed to perinatal NRTIs died of mitochondrial disorders or that living exposed children had symptoms of mitochondrial dysfunction.

Prevention of HIV infection in children.

The threshold of a new century is an opportune time to review advances in the prevention of HIV infection in children. In the United States, progress in the ability to virtually eliminate perinatal HIV transmission that was unthinkable just a few years ago has been achieved. Clinicians providing care to pregnant women should educate and counsel women about HIV and strongly recommend that they be tested. They should also counsel HIV-infected women about the means available to substantially decrease the risk for HIV transmission to their infants (e.g., antiretroviral drug use, avoidance of breast-feeding, elective C-section, encouraging pregnant women to use barrier methods during sexual intercourse, and to discontinue injection drug use). This article has highlighted some of the remaining challenges that constitute barriers to achieving maximal decrease of HIV infection in children. Studies conducted in resource-poor countries have added greatly to the understanding of vertical transmission of HIV, and they are now leading to practical and affordable approaches to reduce vertical HIV transmission world-wide. The results of this research must lead to coordinated public health action and a global political commitment to extend the benefits of antiretroviral drug prophylaxis that now exist widely in the United States to more resource-poor countries.

Update on perinatal HIV transmission.

Over the past decade, much progress has been made in understanding the risk factors and timing of perinatal HIV transmission. Even more impressive have been the successful clinical trials with antiretrovirals, such as ZDV, ZDV-3TC, and nevirapine, that demonstrated significant reductions in the risk for infant infection. Within the United States and Europe, these trial results have led to rapid implementation and dramatic decreases in new perinatal HIV cases since 1994. An immediate challenge is to rapidly translate the short-course antiretroviral trial results with ZDV and nevirapine into public health policy and practice in resource-poor settings, where almost 600,000 neonates continue to become infected by mother-infant HIV transmission each year. Physicians must also test strategies to further decrease the risk for infant HIV infection during the breast-feeding period.

Women and HIV. Epidemiology and global overview.

The global HIV-1 epidemic in women continues to expand at an alarming rate. More than 11 million women are currently estimated to be HIV-infected, with the majority living in sub-Saharan Africa. The primary risk factor for HIV infection in women is unprotected heterosexual intercourse. Several cofactors may influence a woman's risk for HIV acquisition. These include the presence of other STDs, the prevalence of HIV in the population, engagement in high-risk sexual behaviors at a young age, an increased number of sexual partners, HIV illness severity in an infected partner, host immunogenetic responses, hormonal and other local effects in the female genital tract, and viral characteristics. The general clinical findings in women with HIV disease are similar to those in HIV-infected men. Some studies have noted higher rates of esophageal candidiasis and decreased rates of Kaposi's sarcoma in women when compared with men. Overall disease progression and survival in women and men are similar once an adjustment is made for other important risk factors such as the time of seroconversion, the receipt of antiretrovirals, and baseline CD4 cell counts. Women with HIV have a high frequency of a number of diseases of the reproductive tract, including low-grade cervical dysplasia and vulvovaginal candidiasis. Despite progress in understanding the risk factors for HIV transmission to women and the variables related to disease progression, major research questions remain. These include the role of hormonal contraceptives in the risk for HIV acquisition, the primary mechanism of infection, and host systemic as well as local hormonal and immune responses in the female reproductive tract that may alter the risk of HIV infection. Over the next decade, it is anticipated that the quality of life and length of survival will improve dramatically for both HIV-infected women and men in settings in which new highly active combination antiretroviral therapy is available and affordable. Unfortunately, in most of the world, these antiretroviral drugs are not available for the treatment of the vast numbers of individuals infected by HIV. Therefore, development of successful strategies for primary prevention of HIV infection in women must be a top public health priority.

PIP: The global HIV epidemic in women continues to expand, primarily as a result of unprotected heterosexual intercourse. Women's risk of HIV acquisition is affected by cofactors such as the presence of other sexually transmitted diseases, the prevalence of HIV in the population, the practice of high-risk sexual behaviors at a young age, an increased number of sexual partners, HIV illness severity in an infected partner, host immunogenetic responses, hormonal and other local effects in the female genital tract, and viral characteristics. Although the general clinical findings in HIV-infected men and women are similar, women also have a high frequency of reproductive tract diseases such as low-grade cervical dysplasia and vulvovaginal candidiasis. Further research is needed to assess the role of hormonal contraception in the risk for HIV acquisition, the primary mechanism of infection, and host systemic as well as local hormonal and immune responses in the female reproductive tract that may alter HIV risk. Although combination antiretroviral therapy has demonstrated the ability to improve the quality of life and survival time of HIV-infected men and women, the high cost of such treatment renders it inaccessible to the majority of HIV-infected patients. Thus, the development of successful strategies for primary prevention of HIV infection--especially among women--remains a top public health priority.

Preschool risk factors as predictors of early school performance.

The relative importance of selected developmental, medical, and social factors in assessing a child's early academic potential was evaluated prospectively in a rural southern school district. Two hundred and ten (210) preschoolers were given the Sprigle School Readiness Screening Test (SSRST) and the Beery Test of Visual Motor Integration (VMI) while physicians rated the children's attention span. A parental questionnaire assessed medical, behavioral, social, and family variables. Follow-up school data were available on 176 children (84%). Using regression techniques, reading and math achievement scores were directly correlated with maternal education, SSRST and VMI results, and lack of family history of learning problems, whereas grade failure was associated with low VMI scores, decreased maternal education, boys with late birthdays, and family history of learning problems. Medical problems and parental preschool behavior concerns were unrelated to school achievement, but physician rating of preschool attention span showed a significant correlation with reading and math scores. A 0-11 Risk Index of School Capability (RISC) scale based on data analyses was developed to rate a preschooler's early academic potential. A score of 7 or above had a 98% positive predictive value of successful grade completion, whereas a score of 3 or below had a 70% predictive value for grade failure. The value of assessing the scores of the VMI and SSRST alone was also considered, but was found less useful. This study demonstrates the importance of evaluating a number of risk factors in assessing a preschooler's early academic potential. Such data can be used to focus school resources for children at increased risk for grade failure.

Parental and pediatric trainee knowledge of development.

This study evaluated the fund of knowledge about normal development and developmental disabilities of parents and pediatric residents. A 23-item questionnaire was administered to 91 parents of children who were being evaluated at the Division for Disorders of Development and Learning (DDDL) and to 20 pediatric residents at the University of North Carolina (UNC). The physicians-in-training were provided with an additional 26 questions on development, as well as a rating scale of "personal comfort" in discussing three specific developmental disabilities with parents (epilepsy, hyperactivity, and mental retardation). On the series of identical questions, pediatric residents scored significantly better than parents; the mean number correct was 19.4/23 (residents) versus 15.9/23 (parents). However, in both groups there were notable errors. Incorrect responses by 25% or more of parents and/or physicians were labeled "common misconceptions." Sixteen parent and 15 physician common misconceptions were identified in the areas of normal development and developmental disabilities. The pediatric residents revealed greater comfort in discussing the medical problem (epilepsy) than the two developmental problems (mental retardation and learning disabilities/hyperactivity). The study revealed important and similar gaps in the pediatric trainees' and parents' knowledge of development. These deficiencies need to be addressed in the training of pediatric residents in order to help them better understand the needs of families of developmentally disabled and normal children.