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Although expression of E6/E7 antigens by HPV-related cancers presents an opportunity for immunologic targeting, there are currently no HPV-specific FDA-approved immunotherapies to treat HPV-related cancers. The IMMUNOCERV trial was designed to test the hypothesis that PDS0101, a novel, subcutaneously administered HPV-specific vaccine containing peptide pools encoding E6/E7 antigens, would be safe and effective in combination with standard of care chemoradiation for locally advanced HPV-related cervical cancer. In this single-arm, phase 2 study (NCT04580771), patients received PDS0101 at Day -10, 7, 28, and 49 (+/- 5 days) in relation to the start of chemoradiation. Key eligibility criteria included newly diagnosed, biopsy-proven locally advanced squamous cell carcinoma of the cervix (tumor ≥5cm and/or nodal disease), age greater than 17, and ECOG ≤2. The trial was designed to include 35 patients. Adverse events were assessed using the CTCAE version 5.0. The primary endpoint for this study was the rate of clinically significant grade ≥3 acute toxicities from first vaccine injection up to 30 days following completion of chemoradiation (Day -10 to day 80). Prespecified secondary endpoints included the rate of complete metabolic response (CMR) on Day 170 PET CT (± 14 days), rate of ≥90% gross tumor volume reduction (GTVR) on Day 35 MRI (± 5 days), progression-free survival (PFS), and overall survival (OS) at 12 and 18 months after completion of chemoradiation. Seventeen patients were enrolled before the trial was closed due to a change in the standard of care. Median follow up was 575 days. Acute grade 3+ adverse events occurred in eight patients (47%). Toxicities related to PDS0101 injection were limited to injection site reaction in twelve patients (71%) and single reports of urticarial allergic reaction (Grade 3) and pain (Grade 2). Five patients (29%) experienced >90% GTVR at Day 35 MRI compared to baseline. CMR at 4 month follow up were achieved in 10 of 17 patients (59%) including seven patients who completed all five prescribed doses of PDS0101 (88%). Twelve, 18, and 36-month PFS were 82.4%, 74.9%, and 74.9%. Twelve, 18, and 36-month DFS were each 82.35%. OS at 12, 18, and 36 months was 92.9%, 84.4%, and 84.4%. GTVR on Day 35 MRI >75% (HR 0.064, 95% CI = 0.004-0.92, P = 0.001) and receipt of all five doses of PDS0101 (HR 0.27, 95% CI = 0.02-0.91, P = 0.040) were associated with improved PFS. All patients who received five doses of PDS0101 were disease free and alive at 36 months. In this final report of the IMMUNOCERV clinical trial, PDS0101 was safe and well-tolerated, and receipt of all prescribed doses of PDS0101 was associated with improved PFS. Further investigation of PDS0101 in cervical cancer in combination with pembrolizumab is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Craniopharyngiomas can be aggressive leading to significant complications and morbidity. It is not clear whether there are any predictive factors for incidence or outcomes. Our aim was therefore to record the incidence, presentation, characteristics and progression of paediatric craniopharyngiomas in the West of Scotland., Method: Retrospective case note review for children diagnosed with paediatric craniopharyngiomas at the Royal Hospital for Children Glasgow, from 1995 to 2021 was conducted. All analyses were conducted using GraphPad Prism 9.4.0., Results: Of 21 patients diagnosed with craniopharyngiomas, the most common presenting symptoms were headaches (17/21, 81%); visual impairment (13/21, 62%); vomiting (9/21, 43%) and growth failure (7/21, 33%). Seventeen (81%) patients underwent hydrocephalus and/or resection surgery within 3 months of diagnosis, usually within the first 2 weeks (13/21, 62%). Subtotal resection surgeries were performed in 71% of patients, and median time between subsequent resection surgeries for tumour recurrence was 4 years (0,11). BMI SDS increased at 5 year follow-up (p = 0.021) with 43% being obese (BMI > + 2SD). More patients acquired hypopituitarism post-operatively (14/16, 88%) compared to pre-operatively (4/15, 27%). A greater incidence of craniopharyngiomas were reported in more affluent areas (10/21, 48%) (SIMD score 8-10) compared to more deprived areas (6/10, 29%) (SIMD score 1-3). Five patients (24%) died with a median time between diagnosis and death of 9 years (6,13)., Conclusion: Over 25 years the management of craniopharyngioma has changed substantially. Co-morbidities such as obesity are difficult to manage post-operatively and mortality risk can be up to 25% according to our cohort., (© 2024. Crown.)

Background: With overpopulation contributing to the depletion of planetary resources, the high rates of unintended pregnancies in India are a cause for concern. Despite the free supply of contraception options within India's national family planning initiatives, women are generally offered hormonal options as temporary spacing methods. However, female condoms, a much neglected but potent woman initiated, non-hormonal multipurpose prevention device, are yet to be considered for inclusion in India's contraceptive cafeteria. Thus, we aim to examine the place of female condoms among the contraceptive options, by analysing the perceptions of key stakeholders regarding its advantages and disadvantages, along with their opinions on how female condoms should be promoted., Methods: We used purposive sampling to recruit and interview potential users and dispensers of the female condom. The interview participants visited or worked at family planning clinics in Pune at Smt. Kashibai Navale Medical College and General Hospital (SKNMC-GH), its urban and rural outreach clinics, and at Saheli (a non-governmental organisation for female sex workers). We conducted semi-structured interviews and coded our data inductively., Results: We interviewed 5 rural women, 20 urban women (including 10 female sex workers), 5 male partners of female sex workers, and 5 family planning healthcare providers. Nearly half (12/25) of the women we interviewed, said that they were eager to use female condoms in the future. Many participants perceived female condoms to be an instrument to empower women to be in control of their sexual and reproductive lives (15/35), and that it provided user comfort and confidence (4/35). Their perceived disadvantages are that they are relatively more expensive (6/35), users have limited experience (9/35), and women who buy or use them may be stigmatised and feel embarrassed (4/35). Yet, nearly three-quarters of potential users (21/30) and most healthcare providers (4/5), were confident that female condoms could become popular following extensive promotional campaigns, interventions to improve availability and access, and initiatives to enhance the knowledge of female users., Conclusions: Female condoms have garnered support from both users and dispensers and have the potential to be widely adopted in India if family planning initiatives which increase awareness, knowledge, and access are systematically undertaken as with other contraceptive options., (© 2022. The Author(s).)

In 2020 the COVID-19 pandemic caused millions to lose their jobs and, consequently, their employer-sponsored health insurance. Enacted in 2010, the Affordable Care Act (ACA) created safeguards for such events by expanding Medicaid coverage and establishing Marketplaces through which people could purchase health insurance. Using a novel national data set with information on ACA-compliant individual insurance plans, we found large increases in Marketplace enrollment in 2020 compared with 2019 but with varying percentage increases and spending risk implications across states. States that did not expand Medicaid had enrollment and spending risk increases. States that expanded Medicaid but did not relax 2020 Marketplace enrollment criteria also had spending risk increases. In contrast, states that expanded Medicaid and relaxed 2020 enrollment criteria experienced enrollment increases without spending risk changes. The findings are reassuring with respect to the ability of Marketplaces to buffer employment shocks, but they also provide cautionary signals that risks and premiums could begin to rise either in the absence of Medicaid expansion or when Marketplace enrollment is constrained.

Hemorrhagic cystitis is a life-threatening condition in which the transitional epithelium and blood vessels of the bladder necrose leading to severe hematuria, abdominal pain, and voiding lower urinary tract symptoms. Etiology includes chemotherapy (cyclophosphamide, ifosfamide, busulfan), radiotherapy, or infectious agents. We present a pediatric case of a 15-year-old boy with medulloblastoma who developed hemorrhagic cystitis following cisplatin chemotherapy. All other causes were ruled out and it is therefore likely that the agent, in this case, was cisplatin, which has never had hemorrhagic cystitis reported as a side effect. We also suggest a mechanism for urothelial injury centered around OCT-2 receptors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Environmental exposures have a significant effect on respiratory and sleep symptoms in young children. Although the effect of air pollution on the respiratory symptoms in young children is well-established, less is known about the effect of household environmental characteristics and practices on wheeze and sleep concerns., Aims: The aim of this pilot study is to explore the association between household environmental characteristics and practices with the symptoms of wheezing and sleep concerns in the past year in a convenience sample of young Indian children., Materials and Methods: A detailed questionnaire about the child's home environment and respiratory and sleep symptoms was administered to the caregivers of 190 outpatients aged between 6 months and 5 years old at a teaching hospital., Results: Indoor environmental characteristics and cleaning techniques were analyzed for the association with wheeze and sleep disorders. Half (50%) of the cohort had the symptoms of wheezing and 21% had occasional or frequent sleep concerns. Sleeping with a stuffed toy was significantly associated with both wheezing and sleep concerns (P = 0.05)., Conclusions: : Sleeping with a stuffed toy was a risk factor for wheeze and a risk factor for sleep disorders independent of wheeze., Competing Interests: None

Objectives: To estimate the population prevalence of clinically significant symptoms of depression, generalised anxiety, thoughts of being better off dead, irritability, and high optimism about the future, and of direct experience of COVID-19, loss of employment caused by COVID-19 restrictions, worry about contracting COVID-19, or major disadvantage because of the restrictions; to examine the relationship between these experiences and reporting mental symptoms., Design, Setting, Participants: Anonymous online survey of adult Australian residents, 3 April - 2 May 2020., Main Outcome Measures: Self-reported psychological status during the preceding fortnight assessed with the Patient Health Questionnaire 9 (PHQ-9; symptoms of depression) and the Generalised Anxiety Disorder Scale (GAD-7). Optimism about the future was assessed with a 10-point study-specific visual analogue scale., Results: 13 829 respondents contributed complete response data. The estimated prevalence of clinically significant symptoms of depression (PHQ-9 ≥ 10) was 27.6% (95% CI, 26.1-29.1%) and of clinically significant symptoms of anxiety (GAD-7 ≥ 10) 21.0% (95% CI, 19.6-22.4%); 14.6% of respondents (95% CI, 13.5-16.0%) reported thoughts of being better off dead or self-harm (PHQ-9, item 9) on at least some days and 59.2% (95% CI, 57.6-60.7%) that they were more irritable (GAD-7, item 6). An estimated 28.3% of respondents (95% CI, 27.1-29.6%) reported great optimism about the future (score ≥ 8). People who had lost jobs, were worried about contracting COVID-19, or for whom the restrictions had a highly adverse impact on daily life were more likely to report symptoms of depression or anxiety, and less likely to report high optimism than people without these experiences., Conclusions: Mental health problems were widespread among Australians during the first month of the stage two COVID-19 restrictions; in addition, about one-quarter of respondents reported mild to moderate symptoms of depression or anxiety. A public mental health response that includes universal, selective and indicated clinical interventions is needed., (© 2020 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Researchers and advocates have increasingly called for adolescent participation in clinical trials for new HIV prevention products, particularly adolescent girls in areas most affected by the epidemic. However, recent trials have highlighted the challenges for young women and adolescents to be able to effectively use new products that require daily dosing. This analysis provides a highly relevant context for this challenging environment by examining community members acceptability of adolescent girls' participation in clinical trials for new HIV prevention products. We conducted 41 in-depth interviews in Dar es Salaam, Tanzania and Pune, India with 22 key informants (KIs). Cultural perspectives on adolescent sexuality varied between countries, with KIs in Tanzania more readily acknowledging adolescent girls' sexual activity than KIs in India. KIs in both countries felt strongly adolescents must be well-informed about research concepts prior to participation, and emphasis should be given to preventative misconception. Despite concern in both countries that the trials might be seen as encouraging sexual behavior, KIs in Tanzania overwhelmingly supported adolescent inclusion, whereas KIs in India were more cautious. Involving adolescent girls in clinical trials for new HIV prevention products is potentially acceptable, although meaningful community engagement will be necessary.

Nevirapine (NVP) therapy is associated with a high risk of serious liver injury and skin rash. Treatment of Brown Norway rats with NVP causes an immune-mediated skin rash. Even though NVP does not cause serious liver injury in wildtype animals, incubation of hepatocytes with NVP leads to the release of presumably danger-associated molecular pattern molecules (DAMPs), which activate macrophages. In this study, we examined the liver biopsies of Brown Norway rats treated with NVP to determine the histologic correlate to the release of DAMPs by hepatocytes. In vivo, debris from necrotic hepatocytes and endothelial cells were present in the liver sinusoids, a condition that can trigger an immune response. In addition to mitochondrial, hepatocytic, and endothelial damage, the drug induced large hepatocytic inclusions composed of lipid droplets surrounded by concentric whorls of smooth endoplasmic reticulum (SER) cisternae-lipid-SER (LSER) inclusions, which were deposited in the sinusoids. NVP is lipid soluble, and these LSER inclusions may be sinks of NVP or its metabolites. LSERs are deposited in the blood stream where they may be picked up by lymph nodes and contribute to initiation of an immune response leading to serious liver injury or skin rash. LSERs migration from liver to the blood stream may signify a novel mechanism of drug exocytosis.

Purpose: Selection of the most appropriate chemotherapy dosing regimens for neonates treated within the first weeks of life represents a significant clinical dilemma. Due to a lack of information relating to the clinical pharmacology of anticancer drugs in these challenging patients, current dosing guidelines are based on limited scientific rationale. In the current study, we investigate the utilisation of therapeutic drug monitoring approaches in neonates with localised hepatoblastoma, Wilms' tumour and stage 4S neuroblastoma, being treated with widely used anticancer drugs., Methods: Plasma concentrations of cisplatin, vincristine, etoposide and carboplatin were quantified in two neonates being treated within the first 3 weeks of life and in a 32-week preterm infant treated at a gestational age of 40 weeks. Therapeutic drug monitoring was carried out where appropriate, based on the pharmacokinetic data obtained in conjunction with clinical response and toxicity., Results: Treatment of a child aged 2 weeks with a recommended cisplatin dose reduction for weight to 1.8 mg/kg resulted in achievement of unbound cisplatin plasma concentrations of 0.01-0.08 µg/mL, markedly lower than exposures previously reported in infants and older children. A dose increase to 2.7 mg/kg was implemented, leading to the achievement of levels more in-line with those previously reported. This increased dose level was well tolerated over six courses of treatment, resulting in a good response to cisplatin monotherapy and the patient remains in remission at 3.5 years. In contrast, a 50 % vincristine dose reduction for weight in a 3-week-old neonate resulted in plasma concentrations comparable to levels observed in older children, leading to successful treatment and continued remission at 2 years. In a third patient, etoposide and carboplatin clearance values normalised to body weight were comparable to those reported in older children, resulting in comparatively lower exposures following reduced dosing., Conclusions: The current report provides unique data on the pharmacokinetics of several widely used anticancer drugs in neonates treated within the first few weeks of life. The provision of these data acts as a useful reference point to support future dosing decisions to be made by clinicians in the treatment of these challenging patients.

13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.

Chyawanprash is an ayurvedic formulation used in Indian traditional medicinal system for its beneficial effect on human health. We investigated the immunostimulatory effects of Chyawanprash (CHY) using in vitro assays evaluating the secretion of cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1beta (IL-1β) and Macrophage Inflammatory Protein-1-alpha (MIP-1-α) from murine bone marrow derived Dendritic Cells (DC) which play pivotal role in immunostimulation. The effects of CHY on phagocytosis in murine macrophages (RAW264.7) and Natural Killer (NK) cell activity were also investigated. At non-cytotoxic concentrations (20-500 μg/ml), CHY enhanced the secretion of all the three cytokines from DC. CHY also stimulated both, macrophage (RAW264.7) as well as NK cell activity, in vitro. In conclusion, the data substantiates the immunoprotective role of CHY at cellular level mediated by immunostimulation in key immune cells viz. dendritic Cells, macrophages and NK cells.

Background: India has among the highest rates of infant malnutrition. Few studies investigating the growth patterns of HIV-exposed infants in India or the impact of timing of HIV infection on growth in settings such as India exist., Methods: We used data from the Six Week Extended Nevirapine (SWEN) trial to compare the growth patterns of HIV-infected and HIV-exposed but uninfected infants accounting for timing of HIV infection, and to identify risk factors for stunting, underweight and wasting. Growth and timing of HIV infection were assessed at weeks 1, 2, 4, 6, 10, 14 weeks and 6, 9, 12 months of life. Random effects multivariable logistic regression method was used to assess factors associated with stunting, underweight and wasting., Results: Among 737 HIV-exposed infants, 93 (13%) were HIV-infected by 12 months of age. Among HIV-infected and uninfected infants, baseline prevalence of stunting (48% vs. 46%), underweight (27% vs. 26%) and wasting (7% vs. 11%) was similar (p>0.29), but by 12 months stunting and underweight, but not wasting, were significantly higher in HIV-infected infants (80% vs. 56%, 52% vs. 29%, p< 0.0001; 5% vs. 6%, p=0.65, respectively). These differences rapidly manifested within 4-6 weeks of birth. Infants infected in utero had the worst growth outcomes during the follow-up period. SWEN was associated with non-significant reductions in stunting and underweight among HIV-infected infants and significantly less wasting in HIV-uninfected infants. In multivariate analysis, maternal CD4 < 250, infant HIV status, less breastfeeding, low birth weight, non-vaginal delivery, and infant gestational age were significant risk factors for underweight and stunting., Conclusion: Baseline stunting and underweight was high in both HIV-infected and uninfected infants; growth indices diverged early and were impacted by timing of infection and SWEN prophylaxis. Early growth monitoring of all HIV-exposed infants is an important low-cost strategy for improving health and survival outcomes of these infants., Trial Registration: NCT00061321.

Little is known about birth outcomes for HIV-infected women in India. We examine maternal and neonatal birth outcomes in HIV-infected women within the context of enhanced pre-natal care associated with a randomized clinical trial conducted in Pune, India. Birth outcomes of 212 HIV-infected pregnant women were compared with those of 130 HIV-uninfected pregnant women attending a government tertiary care hospital between 2002 and 2004. These women and children were participating in the Six Week Extended-Dose Nevirapine (SWEN) study. Birth outcomes and maternal morbidity data were collected at delivery. We found no differences between HIV-infected and uninfected pregnant women with respect to the proportion with elevated intrapartum blood pressure, eclampsia, oligohydramnios, intrauterine growth restriction (IUGR), preterm delivery, or caesarean section (p>0.05). HIV-infected women were more likely to have peri-partum fever (3% versus 0%, p=0.04). There were no differences in neonatal parameters such as low birth weight (LBW), infants who were small for gestational age, or those having congenital anomalies (p>0.05). Compared with infants of HIV-infected women enrolled antenatally, infants of HIV-infected women enrolled in the post-partum ward had a higher risk of pre-term delivery (20% versus 8%, p=0.02) and LBW (41% versus 22%, p=0.002). HIV-infected women in this cohort in India were not found to have significant negative birth outcomes. Antenatal care was important as those not having received any antenatal care prior to deliver were at increased risk of having a pre-term delivery or an infant with LBW. Based on these data, regular antenatal care provided to HIV-infected women can reduce risk of adverse birth outcomes for their infants.

We evaluated tuberculosis (TB) screening among 799 human immunodeficiency virus (HIV)-infected pregnant women in India. Eleven (1.4%) had active TB. The negative predictive value of screening using cough, fever, night sweats, or weight loss was 99.3%. Tuberculin skin test and targeted chest radiography provided no substantial benefit. TB symptom screening, as recommended by the World Health Organization, is effective for ruling out TB in HIV-infected pregnant women.

Efficient induction of antigen-specific immunity is achieved by delivering multiple doses of vaccine formulated with appropriate adjuvants that can harness the benefits of innate immune mediators. The synthetic glycolipid α-galactosylceramide (α-GalCer) is a potent activator of NKT cells, a major innate immune mediator cell type effective in inducing maturation of DCs for efficient presentation of co-administered antigens. However, systemic administration of α-GalCer results in NKT cell anergy in which the cells are unresponsive to subsequent doses of α-GalCer. We show here that α-GalCer delivered as an adjuvant by the intranasal route, as opposed to the intravenous route, enables repeated activation of NKT cells and DCs, resulting in efficient induction of cellular immune responses to co-administered antigens. We show evidence that after intranasal delivery,α-GalCer is selectively presented by DCs for the activation of NKT cells, not B cells. Furthermore, higher levels of PD-1 expression, a potential marker for functional exhaustion of the NKT cells when α-GalCer is delivered by the intravenous route, are not observed after intranasal delivery. These results support a mucosal route of delivery for the utility of α-GalCer as an adjuvant for vaccines, which often requires repeated dosing to achieve durable protective immunity., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: HIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life., Methods: Using data from a prevention of mother-to-child transmission (PMTCT) trial (India SWEN), where HIV-exposed breastfed infants were given extended nevirapine, we measured 12-month infant all-cause and cause-specific hospitalization rates and hospitalization risk factors., Results: Among 737 HIV-exposed Indian infants, 93 (13%) were HIV-infected, 15 (16%) were on HAART, and 260 (35%) were hospitalized 381 times by 12 months of life. Fifty-six percent of the hospitalizations were attributed to infections; gastroenteritis was most common accounting for 31% of infectious hospitalizations. Gastrointestinal-related hospitalizations steadily increased over time, peaking around 9 months. The 12-month all-cause hospitalization, gastroenteritis-related hospitalization, and in-hospital mortality rates were 906/1000 PY, 229/1000 PY, and 35/1000 PY respectively among HIV-infected infants and 497/1000 PY, 107/1000 PY, and 3/1000 PY respectively among HIV-exposed, uninfected infants. Advanced maternal age, infant HIV infection, gestational age, and male sex were associated with higher all-cause hospitalization risk while shorter duration of breastfeeding and abrupt weaning were associated with gastroenteritis-related hospitalization., Conclusions: HIV-exposed Indian infants experience high rates of all-cause and infectious hospitalization (particularly gastroenteritis) and in-hospital mortality. HIV-infected infants are nearly 2-fold more likely to experience hospitalization and 10-fold more likely to die compared to HIV-exposed, uninfected infants. The combination of scaling up HIV PMTCT programs and implementing proven health measures against infections could significantly reduce hospitalization morbidity and mortality among HIV-exposed Indian infants.

Introduction: Malignant tumours of the central nervous system (CNS) represent the second most common cancer type in the paediatric population of developed countries, and mortality caused by CNS tumours is the highest among paediatric cancers. Tumours of mesenchymal origin occurring either as primary or secondary lesions of the central nervous system are very rare in children. This paper describes the case of a 5-year-old non-immunocompromised male who presented with a right frontal primary intracranial leiomyosarcoma associated with large subdural collections., Discussion and Conclusion: Following surgical excision and adjuvant chemoradiotherapy, the patient has remained disease-free for 18 months. The literature is reviewed and the possible association of the chronic subdurals to the later development of the leiomyosarcoma explored.

Background: Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life., Methods/findings: Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission., Conclusions/significance: Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis., Trial Registration: ClinicalTrials.gov NCT00061321.

Background: The risk for occupational exposure to HIV has been well characterized in the developed world, but limited information is available about this transmission risk in resource-constrained settings facing the largest burden of HIV infection. In addition, the feasibility and utilization of post-exposure prophylaxis (PEP) programs in these settings are unclear. Therefore, we examined the rate and characteristics of occupational exposure to HIV and the utilization of PEP among health care workers (HCW) in a large, urban government teaching hospital in Pune, India., Methods: Demographic and clinical data on occupational exposures and their management were prospectively collected from January 2003-December 2005. US Centers for Diseases Control guidelines were utilized to define risk exposures, for which PEP was recommended. Incidence rates of reported exposures and trends in PEP utilization were examined using logistic regression., Results: Of 1955 HCW, 557 exposures were reported by 484 HCW with an incidence of 9.5 exposures per 100 person-years (PY). Housestaff, particularly interns, reported the greatest number of exposures with an annual incidence of 47.0 per 100 PY. Personal protective equipment (PPE) was used in only 55.1% of these exposures. The incidence of high-risk exposures was 6.8/100 PY (n = 339); 49.1% occurred during a procedure or disposing of equipment and 265 (80.0%) received a stat dose of PEP. After excluding cases in which the source tested HIV negative, 48.4% of high-risk cases began an extended PEP regimen, of whom only 49.5% completed it. There were no HIV or Hepatitis B seroconversions identified. Extended PEP was continued unnecessarily in 7 (35%) of 20 cases who were confirmed to be HIV-negative. Over time, there was a significant reduction in proportion of percutaneous exposures and high-risk exposures (p < 0.01) and an increase in PEP utilization for high risk exposures (44% in 2003 to 100% in 2005, p = 0.002)., Conclusion: Housestaff are a vulnerable population at high risk for bloodborne exposures in teaching hospital settings in India. With implementation of a hospital-wide PEP program, there was an encouraging decrease of high-risk exposures over time and appropriate use of PEP. However, overall use of PPE was low, suggesting further measures are needed to prevent occupational exposures in India.

HIV-positive women of reproductive age face challenges in decision making related to pregnancy. Understanding factors influencing repeat pregnancies in women with known HIV status are necessary to guide interventions and counseling strategies to better inform and support them. We compared three groups of women attending a large antenatal clinic in Pune, India. They include: Group A--63 HIV-positive women coming for care for a repeat pregnancy after being diagnosed in a previous pregnancy; Group B--64 HIV-negative (repeat) pregnant women attending this antenatal clinic; and Group C--63 HIV-positive non-pregnant women currently enrolled in an ongoing clinical trial. Comparisons of Group A and B indicate that the likelihood of unplanned repeat pregnancies was significantly higher in HIV-positive (70%) than HIV-negative (36%) women (OR=4.1, CI: 2.0-8.7). Inability to terminate the pregnancy (31%) and familial obligations (40%) appear to be important for continuing the unplanned repeat pregnancy. Despite high reported contraceptive use by HIV-positive women, pregnancies still occurred. Death of their youngest child is an important factor as 21% of HIV-positive pregnant women lost their youngest child compared with 3% of HIV-negative women and 3% of HIV-positive non-pregnant women (p<0.001). Repeat pregnancies were more likely to occur for women who did not disclose their HIV status to their spouse. Thus the majority of the repeat pregnancies for HIV-positive women were both unplanned and unwanted.

Despite an estimated 70,000 Indian children living with HIV infection, little is known about India's pediatric HIV epidemic. Generalizations about epidemiology, natural history, and treatment outcomes from other resource-limited settings (RLS) may be inaccurate for several biologic and social reasons. A review of the Indian literature is needed to optimize country-specific HIV management and examine these generalizations. MEDLINE and EMBASE were searched for articles published in English by November 2007 on HIV-infected, Indian children (0-18 years) that detailed epidemiology, natural history, or treatment. Articles with original, extractable data were selected and summarized using descriptive statistics. Of 370 citations, 58 studies were included in this review (median study size 24 children). Significant heterogeneity was noted among the studies. HIV infection was reported nearly twice as often in males (male/female ratio 1.9) and diagnosed earlier (4.7 years) than in other RLS. Over 2% of hospitalized children were reported to be HIV-infected. The reported mortality among HIV-infected newborns of 22% at 18 months was lower than other RLS. Improved anthropometrics were the only consistently reported and comparable benefit of short-term HAART to other RLS. Review of the Indian literature yielded potentially unique epidemiology and natural history compared to other RLS. However, important questions about the accuracy and representativeness of the Indian data limit its generalizability and comparability. Targeted interventions to curb India's pediatric HIV epidemic require urgent clarification of these findings. If such differences truly exist, management guidelines should be tailored accordingly.

Background: Some studies support the use of total lymphocyte count (TLC) as a surrogate marker for CD4 cell count to guide antiretroviral therapy (ART) initiation. However, most of these studies have focused on nonpregnant adults. In light of expanding ART access through prevention of mother-to-child transmission (PMTCT)-plus programs in resource-limited settings, we assessed the sensitivity, specificity, and positive predictive value (PPV) of TLC for predicting low CD4 counts in antepartum and postpartum women in Pune, India., Methods: CD4, TLC, and hemoglobin were measured at third trimester, delivery, and 6, 9, and 12 months postpartum (PP) in a cohort of 779 HIV-infected women. Optimal TLC cutoff for predicting CD4 <200 cells/mm3 was determined via logistic regression where sensitivity, specificity, PPV, and an area under the receiver operating characteristic (ROC) curve were calculated., Results: Among the 779 women enrolled, 16% had WHO clinical stage 2 or higher and 7.9% had CD4 <200 cells/mm3. Using 2689 TLC-CD4 pairs, the sensitivity, specificity, and PPV of TLC <1200 cells/mm3 for predicting CD4 <200 cells/mm3 was 59%, 94%, and 47%, respectively. The sensitivity of TLC <1200 cells/mm3 cutoff ranged between 57% and 62% for time points evaluated. Addition of hemoglobin <12 g/dL or <11 g/dL increased the sensitivity of TLC to 74% to 92% for predicting CD4 <200 cells/mm3 but decreased the specificity to 33% to 69% compared to TLC alone. A combination of TLC, hemoglobin, and WHO clinical staging had the highest sensitivity but lowest specificity compared to other possible combinations or use of TLC alone. The sensitivity and specificity of TLC <1200 cells/mm3 to predict a CD4 <350 cells/mm3 was 31% and 99%, respectively., Conclusions: Our data suggest that antepartum and PP women with TLC <1200 cells/mm3 are likely to have CD4 <200 cells/mm3. However, the sensitivity of this TLC cutoff was low. Between 45% and 64% of antepartum and PP women requiring initiation of ART may not be identified by using TLC alone as a surrogate marker for CD4 <200 cells/mm3. The WHO-recommended TLC cutoff of <1200 cells/mm3 is not optimal for identifying antepartum and PP Indian women who require ART.

Background: A single recent study has suggested a decrease in HIV risk for women attending antenatal clinics (ANCs) in southern India. Yet, some have questioned the validity of the Indian national surveillance data and analyses. Previous studies suggest that the only major HIV risk factor for married Indian women is the risk behavior of their husbands. Therefore, to address concerns about potential selection bias in the analysis of sentinel surveillance data from multiple sites, we estimated the trajectory of HIV transmission rates among recently married, monogamous, primigravid women attending a single large ANC in Pune, India., Methods: Participants were self-referred, young, primigravid women from 18 to 27 years of age consenting to HIV screening. Time trends in HIV prevalence over 3.5 years were evaluated by logistic regression adjusted for age. HIV incidence was estimated by dividing the number of HIV-infected mothers by an estimate of exposure person-time, which was an estimate of the average age-specific duration of marriage., Results: Between August 16, 2002 and February 28, 2006, 30,085 (79.5%) of 37,858 pregnant women consented to HIV screening; 10,982 (36.5%) were primigravid and their age range was from 18 to 27 years. HIV infection risk declined over 3.5 years among primigravid women. An estimated 19,739 person-years (PYs) of exposure yielded an overall HIV incidence rate 1.25/100 PYs (95% confidence interval [CI]: 1.10 to 1.42). Estimated HIV incidence decreased from 2.2/100 PYs (95% CI: 1.6 to 3.0) in 2002 to 2003 to 0.73/100 PYs (95% CI: 0.5 to 1.0) in 2006., Discussion: HIV infection risk among young primigravid women in Pune seems to have decreased over the past 3.5 years. A decreasing HIV risk among pregnant women in Pune would also decrease the number of HIV-exposed infants. We hypothesize that decreased high-risk sexual behavior among young recently married men is most likely contributing to a decreasing risk to their wives and children in Pune.

Background & Objective: The percentage of HIV cases attributed to mother-to-child transmission (MTCT) has increased several fold in recent years. No reports are available on HIV MTCT rates among HIV-infected choosing not be exclusively breastfeed their infants in India. We examined HIV MTCT rates among 41 Indian women in a prospective cohort who chose predominantly not to exclusively breastfeed., Methods: Of the 41 women, 27 (66%) received MTCT prophylaxis: 3 received short course zidovudine (AZT), 19 single-dose nevirapine (NVP), and 5 both AZT and NVP. Maternal HIV-I RNA levels (viral load) were measured at the time of delivery. Infants were tested for HIV-1 infection by PCR up to 11 times is first year of life and viral load was measured in PCR positive infants., Results: All infants received single dose NVP. Thirty two (76%) infants were exclusively formula-fed, 10 (24%) were mixed fed. Four infants were diagnosed with HIV infection for an overall 12- month transmission probability of 8 per cent [95% confidence interval (CI) of 3.2 to 22.1%]. Restricting analysis to 31 women who exclusively formula-fed, only one (3.1%) transmission event occurred. The 41 HIV-infected women gave birth to 42 live-born infants., Interpretation & Conclusion: Our data from a small cohort of HIV-infected women suggest that short-course AZT or single dose NVP are effective in reducing MTCT in an Indian setting. Larger studies are needed to assess HIV MTCT rates in India, but in this small study rates were comparable to that observed among women who chose not to exclusively breastfeed in other resource-limited settings.

Background: In contrast with many other countries, isoniazid preventative therapy is not recommended in clinical care guidelines for human immunodeficiency virus (HIV)-infected persons with latent tuberculosis (TB) in India., Methods: Seven hundred fifteen HIV-infected mothers and their infants were prospectively followed up for 1 year after delivery at a public hospital in Pune, India. Women were evaluated for active TB during regular clinic visits, and tuberculin skin tests were performed. World Health Organization definitions for confirmed, probable, and presumed TB were used. Poisson regression was performed to determine correlates of incident TB, and adjusted probabilities of mortality were calculated., Results: Twenty-four of 715 HIV-infected women who were followed up for 480 postpartum person-years developed TB, yielding a TB incidence of 5.0 cases per 100 person-years (95% confidence interval [CI], 3.2-7.4 cases per 100 person-years). Predictors of incident TB included a baseline CD4 cell count <200 cells/mm(3) (adjusted incident rate ratio [IRR], 7.58; 95% CI, 3.07-18.71), an HIV load >50,000 copies/mL (adjusted IRR, 3.92; 95% CI, 1.69-9.11), and a positive tuberculin skin test result (adjusted IRR, 3.08; 95% CI, 1.27-7.47). Three (12.5%) of 24 women with TB died, compared with 7 (1.0%) of 691 women without TB (IRR, 12.2; 95% CI, 2.03-53.33). Among 23 viable infants with mothers with TB, 2 received a diagnosis of TB. Four infants with mothers with TB died, compared with 28 infants with mothers without TB (IRR, 4.71; 95% CI, 1.19-13.57). Women with incident TB and their infants had a 2.2- and 3.4-fold increased probability of death, respectively, compared with women without active TB and their infants, controlling for factors independently associated with mortality (adjusted IRR, 2.2 [95% CI, 0.6-3.8] and 3.4 [95% CI, 1.22-10.59], respectively)., Conclusions: Among Indian HIV-infected women, we found a high incidence of postpartum TB and associated postpartum maternal and infant death. Active screening and targeted use of isoniazid preventative therapy among HIV-infected women in India should be considered to prevent postpartum maternal TB and associated mother-to-child morbidity and mortality.

Objectives: To determine the prevalence of anemia (serum hemoglobin <10 g/dL) and assess zidovudine use and toxicity in HIV-positive pregnant women in India., Methods: From 2002 through 2006, 24,105 pregnant women in Pune were screened for HIV and anemia. As part of an infant prevention of mother-to-child transmission (PMTCT) trial, enrolled HIV-positive women (n = 467) were assessed for anemia and associated outcomes, comparing women receiving zidovudine for >or=2 weeks versus no zidovudine., Results: The prevalence of anemia was 38.7% in HIV-positive women. Anemic women were as likely as nonanemic women to receive zidovudine. At delivery, regardless of anemia status at enrollment, women receiving >or=2 weeks of zidovudine were 70% less likely to be anemic compared with women receiving no zidovudine (odds ratio = 0.28, 95% confidence interval: 0.14 to 0.57; P < 0.01), received iron and folic acid supplements for longer periods, and had no increased adverse delivery or newborn birth outcomes., Conclusions: A significant proportion of HIV-positive pregnant women in India present for antenatal care with anemia. With concurrent iron and folic acid supplementation, however, zidovudine use is not associated with persistent or worsening anemia or associated adverse outcomes. In Indian community settings, all pregnant HIV-positive women should receive early anemia treatment. Mild anemia should not limit zidovudine use for PMTCT in India.

Aims: To estimate the incidence of active tuberculosis (TB) and study the use of chemoprophylaxis for latent TB in children in Wales, and to identify potential areas for improving prevention and management., Methods: Active surveillance for TB in children aged 0-15 years from July 1996 to December 2003, using the Welsh Paediatric Surveillance Scheme., Results: A total of 232 children, 102 with active TB (2.3 per 100 000) and 130 with latent TB (2.9 per 100 000), were identified. Nearly half (45%) belonged to ethnic minorities (19% were of black African origin), a much higher proportion than the base population. Pulmonary disease was the most common presentation (47%), including six (9%) children who were sputum smear positive. There were 10 cases of disseminated TB, nearly all in white children under 10 years of age. Less than two thirds of eligible children (27/46, 59%) were known to have received BCG immunisation. The source of infection was an adult household contact in most cases, but was not known in 44 cases, particularly among teenagers. Four community outbreaks occurred during the surveillance period, including three in high schools., Conclusion: TB incidence in children in Wales remains low, but the epidemiology is changing with an increasing proportion of cases in black African children. The high proportion of patients with disseminated TB is of particular concern. TB in teenagers was often associated with school outbreaks. Many eligible children do not receive BCG immunisation, indicating further scope for prevention.

Chronic granulomatous disease (CGD) is a rare disorder characterized by recurrent infections, often resulting in impaired quality of life and death. Allogeneic BMT provides a definitive cure for CGD, but carries a significant risk of mortality and morbidity. The risk is higher for those who have invasive fungal infection prior to transplant. Reduced intensity conditioning (RIC) is associated with less toxicity from the conditioning agents and may provide an alternative option for all non-malignant diseases. We report a case of successful allogeneic BMT after RIC for a case of X-linked CGD complicated by severe invasive aspergillosis (IA).

Background: One major concern about adenoviral vectors for repetitive gene delivery is the induction of an immune response to the vector, thus impeding effective gene transduction., Methods: To assess the immune response to the adenoviral vector, repetitive gene dosing was performed into rhesus monkey cervix and C3H mouse skin using the adenoviral vector carrying the lacZ gene. Three repetitive intracervical injections of adenovirus-lacZ were done in the rhesus monkey at the intervals of 4 weeks. Gene expression on the second and third injection was completely suppressed., Results: Anti-adenovirus IgG levels and neutralizing antibody titers in the rhesus monkey significantly increased after the first injection of adenovirus. In the C3H mouse, neutralizing antibody titers significantly increased after the first injection of adenovirus-lacZ at more than 10(8) plaque-forming unit (PFU). The repetitive expression of lacZ gene in the mouse skin markedly decreased when the second injection is done more than 2 weeks after the first injection. Chronic low-dose treatment with cyclophosphamide or etoposide markedly suppressed neutralizing antibody titers in the mouse serum and restored the gene expression in the mouse skin on the second and third injection., Conclusions: It is suggested that repetitive gene expression by adenovirus-mediated transfer may be reduced by circulating neutralizing antibodies and could be restored by chronic low-dose treatment with cyclophosphamide or etoposide.

Factors affecting the eligibility and acceptability of voluntary counselling and rapid HIV testing (VCT) were examined among pregnant women presenting in labour in Pune, India. Of the 6702 total women appearing at the delivery room from April 2001 to March 2002, 4638 (69%) were admitted for normal delivery. The remaining women presented with obstetrical complications, delivered immediately or were detected to be in false labour. Overall, 2818 (61%) of the admitted women had been previously tested for HIV during their pregnancy. If previously seen in the hospital's affiliated antenatal clinic, the likelihood of being previously tested was 89%, in contrast to 27% of women having prenatal care elsewhere. Of the admitted women, 3436 (74.3%) were assessed for their eligibility for rapid HIV VCT in the delivery room. Only 1322 (38%) of these women were found to be in early labour and without severe pain or complications, and therefore eligible for rapid HIV screening in the delivery room (DR). Of those 1322 eligible women, only 582 (44%) consented and were tested for HIV, of whom nine (1.6%) were found to be HIV-infected. Of the 1674 women arriving in the DR with no evidence of previous HIV testing, through this DR screening programme, we identified four women with HIV who could now benefit from treatment with ART. Given the high rates of HIV testing in the antenatal clinic at this site and the challenges inherent to conducting DR screening, alternatives such as post-partum testing should be considered to help reduce maternal to infant transmission in this population.

Cisplatin in higher doses have been used routinely in the treatment of childhood tumours including neuroblastoma and germ cell tumors. Amifostine, a broad-spectrum cytoprotector of normal tissues, has been approved by U.S. Food and Drug Administration for use in patients receiving cisplatin. Such administration of amifostine has been reported to reduce cisplatin-related toxicities in some studies, but not all. The authors report a case of severe toxicity with cisplatin in a girl with epithelial cell carcinoma of the ovary despite the use of amifostine.

In 2003, India had over 5.1 million infected individuals living with HIV/AIDS. The percentage of all HIV cases attributed to perinatal transmission has been increasing steadily from 0.33% of total cases in 1999 to 2.80% in 2004. Recent statistics indicate that over 130,000 infants have been infected through this route. Despite recent advances in reducing in utero and interpartum transmission with the use of antiretrovirals, there is a critical need to make infant feeding safer. Current UNAIDS/WHO/UNICEF recommendations stress avoidance of all breast-feeding if replacement feeding fulfills the key requirements of being affordable, feasible, acceptable, sustainable, and safe. In this paper, we examine how the UNAIDS/WHO/UNICEF recommendations have been actualized within the context of an urban government hospital in India. The documented patterns of infant feeding by HIV-positive mothers in Pune, India, from 2000 to 2004, highlight the complexities of making an informed and healthy choice under suboptimal conditions. The data indicate that interpersonal variations in the key requirements greatly influence the optimal practice to minimize mortality risks. Moreover, local information on health outcomes is crucial to tailoring policy recommendations to save lives. We propose the development of a decision-making algorithm that includes factors affecting mother-to-infant transmission, including site-specific data on health risks to the mother and the child. Such an algorithm would allow identification of the healthiest feeding choice and would minimize the pitfalls of promoting homogeneous practices lacking site-specific evidence-based evaluation.

Morphological evaluation of 140 bone marrow aspirations received in haematopathology laboratory with serologically established HIV infection, along with other relevant special haematological tests, was done during 1st Jan 1999 - 31st Dec 2002 at state government run tertiary care General Hospital in Maharashtra state, India. Out of 140 cases: 118 (84.28%) patients had anaemia, 25 (17.86%) had leukopenia, while 13 (9.28%) were thrombocytopenic. Dyserythropoiesis was present in 18 (12.86%) cases, dysmyelopoiesis 37 (26.43%) and micromegakaryocytes were noted in 44 (31.43%) cases. Haemophagocytosis was evident in 8 (5.71%) cases. Plasmacytosis encountered in 120 (85.71%) cases was a common feature. Based on clinical profile and results of other investigations 56 (40%) patients were clinically diagnosed to be of Mycobacterium tuberculosis (TB). Of these, 18 (12.86%) bone marrow aspirates were positive for AFB, Mycobacterium tuberculosis. In 4 cases cryptococci were demonstrated (Mucicarmine stain). There was one case each of Histoplasma capsulatum and leishmaniasis. One patient showed dense parasitemia with Plasmodium falciparum. One patient had immunoblastic lymphoma and showed bone marrow infiltration. Findings in this study strongly indicate that in HIV/AIDS, AFB stain should be done on each marrow aspirate to rule out tuberculosis in countries like India; where TB and AIDS are marching together.

Our objective was to determine the level of HIV/AIDS knowledge of pregnant women in India. In a sub-sample of these women, we documented the extent to which they experienced adverse social and physical difficulties within their home. The study was performed at an urban antenatal hospital clinic in Maharastra, India. From April to September 2001, structured interviews were conducted on 707 randomly selected antenatal clinic patients related to HIV/AIDS knowledge. Of these, 283 were further interviewed to document any social or physical difficulties they experienced. Over 75% of women displayed knowledge of primary transmission routes. Nearly 70% of women demonstrated knowledge of maternal to child transmission, however, only 8% knew of any methods of prevention. TV and written material were more strongly related to knowledge than access to radio messages or conversations with individuals. Thirty per cent of the women experienced physical or mental abuse or their spouse's alcohol and/or drug problems. Women reporting such abuse were more than twice as likely to have adequate HIV/AIDS knowledge compared with women reporting no such abuse. We found no relationship between reported household abuse and educational level of woman, husband, occupation of either partner, language or religion. We found no relationship between HIV status and knowledge of HIV and no relationship between HIV status and risk of abuse in the household. However, the total number of HIV patients in our sample was very small.

This study examined acceptability among pregnant women and their husbands for HIV testing within the antenatal clinic (ANC) and delivery room (DR) of a government hospital in Pune, India from September 2000 to November 2001. Acceptance of HIV counselling and testing was high with 83% of eligible women in the antenatal clinic (851 of 1025) and 68% of eligible women in the delivery room (417 of 613) getting tested on the same day. Structured interviews were conducted on 94 pregnant women in the ANC 50 women in the DR, and 100 husbands who accompanied their wives in the ANC. These data indicated that the majority of women agreed to be tested independently without the need for further consultation with family members, a view that was strongly supported in this sub-sample of accompanying husbands. For delivering women who were not progressing in their labour, counselling in the DR allowed for individual attention to questions and concerns thereby making counselling in the DR feasible.

At the Second International Conference on Cervical Cancer, held April 11-14, 2002, experts in cervical cancer prevention, detection, and treatment reviewed the need for more research in chemoprevention, including prophylactic and therapeutic vaccines, immunomodulators, peptides, and surrogate endpoint biomarkers. Investigators and clinicians noted the need for more rigorous Phase I randomized clinical trials, more attention to the risk factors that can affect study results in this patient population, and validation of optical technologies that will provide valuable quantitative information in real time regarding disease regression and progression. They discussed the role of the human papillomavirus (HPV) in cervical cancer development and the importance of developing strategies to suppress HPV persistence and progression. Results in Phase I randomized clinical trials have been disappointing because few have demonstrated statistically significant regression attributable to the agent tested. Researchers recommended using a transgenic mouse model to test and validate new compounds, initiating vaccine and immunomodulator trials, and developing immunologic surrogate endpoint biomarkers., (Copyright 2003 American Cancer Society.)

Access to safe breast-feeding alternatives for HIV-infected mothers and their infants in many settings is limited. We compared the rates of early postpartum hospitalization of infants born to HIV-infected mothers using different infant-feeding practices in a large government hospital in Pune, India. From March 1, 2000 to November 30, 2001, infants born to HIV-infected mothers were followed in a postpartum clinic. All mothers had received a standard short course of antenatal zidovudine. Infant-feeding practices were assessed within 3 d of delivery, prior to postpartum hospital discharge. Sixty-two of 148 mothers (42%) were breast-feeding their infants. Eighty-six of the mothers (58%) were providing replacement feeding, primarily diluted cow, goat or buffalo milk (top feeding). Twenty-one of the 148 participating infants (14.2%) born during the study period required hospitalization within the 1st 6 mo of life and 6 infants required repeat hospitalization. All hospitalized infants were receiving replacement feeding with a rate of 0.093 hospitalizations per 100 person-days (95% CI, 0.062 to 0.136). The reasons for hospitalization included acute gastroenteritis (48.1%), pneumonia (18.5%), septicemia (11.1%) and jaundice (11.1%). A high risk for early postpartum hospitalization was seen in replacement-fed infants born to HIV-infected mothers in Pune, India. In settings such as India, where access to safe replacement feeding is limited, interventions making exclusive breast-feeding safer for HIV-infected mothers and infants are needed. Such interventions would be valuable additions to the very effective national prevention programs that currently rely on the provision of short-course zidovudine and nevirapine.

Exclusive breast-feeding is widely accepted and advocated in India; however, clinicians are now faced with advising women infected with human immunodeficiency virus (HIV) about the risks and benefits of other infant feeding options. This study assessed factors that influence the infant feeding decisions of HIV-infected mothers in Pune, India. From December 2000 to April 2002, HIV-positive (HIV(+)) pregnant women (n = 101) from a government hospital antenatal clinic were interviewed prepartum about infant feeding intention, feeding practice immediately postpartum and feeding after a minimum of 2 wk postpartum. Of the HIV(+) sample, the last 39 were interviewed more intensively to examine factors affecting feeding decision making. We found that an equal number of HIV(+) women intended to breast-feed (44%) or give top milk (44%) (diluted animal milk). Women who chose to top feed were also more likely to disclose their HIV status to family members. Mixed feeding occurred frequently in our sample (29%); however, for the majority of those (74%), it lasted only 3 d postpartum. The hospital counselor had an important role in assisting women in their intended feeding choice as well as actual practice. The time immediately after delivery was noted as critical for recounseling about infant feeding and further support of the woman's decision, thus lowering the risk of mixed feeding. Lack of funds, poor hygienic conditions and risk of social repercussions were more commonly noted as reasons to breast-feed. Top milk, the alternative for breast-milk used in this population, however, must be investigated further to assess its nutritional value and safety before it can be endorsed widely for infants of HIV(+) women.

Objective: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women., Methods: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA)., Results: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests., Conclusion: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.