Examining the place of the female condom in india's family planning program aqualitative investigation of the attitudes, opinions of key stakeholders in Pune, India.

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.

Mental health of people in Australia in the first month of COVID-19 restrictions: a national survey.

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.

Stakeholder acceptability of adolescent participation in clinical trials for biomedical HIV prevention products: considerations from Tanzania and India.

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.

Growth patterns among HIV-exposed infants receiving nevirapine prophylaxis in Pune, India.

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.

Maternal tuberculosis: a risk factor for mother-to-child transmission of human immunodeficiency virus.

BACKGROUND: Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established. METHODS: The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT. RESULTS: Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53-7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05-6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV. CONCLUSIONS: Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden.

Symptom screening among HIV-infected pregnant women is acceptable and has high negative predictive value for active tuberculosis.

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.

Impact of maternal human immunodeficiency virus infection on pregnancy and birth outcomes in Pune, India.

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.

High rates of all-cause and gastroenteritis-related hospitalization morbidity and mortality among HIV-exposed Indian infants.

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.

The effect of the indoor environment on wheeze- and sleep-related symptoms in young Indian children.

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.

Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

Repeated pregnancy among women with known HIV status in Pune, 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.

High risk for occupational exposure to HIV and utilization of post-exposure prophylaxis in a teaching hospital in Pune, India.

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.

Postpartum tuberculosis incidence and mortality among HIV-infected women and their infants in Pune, India, 2002-2005.

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.

Mother-to-child transmission of HIV among women who chose not to exclusively breastfeed their infants in Pune, India.

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.

Nurses' health education program in India increases HIV knowledge and reduces fear.

Few health care facilities are adequately prepared to manage and care for HIV/AIDS patients in India. Nurses play a critical role in patient care but are often ill-equipped to deal with their own fears of occupational risk and handle the clinical aspects of HIV/AIDS care, leading to stigma and discrimination toward HIV-positive patients. The authors examine the impact of a 4-day HIV/AIDS health education program on knowledge and attitudes of nurses in a government hospital. This education program was developed using a training of trainers model and qualitative research. A total of 21 master trainers underwent 6 days of training and began training of 552 hospital nurses (in 2004-2005). Using a pretest-posttest design, the authors assessed changes in knowledge and attitudes of 371 trained nurses. Significant improvements were seen in nurses' HIV/AIDS knowledge in all areas including care, treatment, and issues of confidentiality and consent. Fear of interaction with people living with HIV/AIDS was reduced significantly. The short course was successful in increasing nurses' knowledge in all aspects. There is great potential to expand this stigma-reduction intervention to other public and private hospitals.

Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.

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.

The Indian pediatric HIV epidemic: a systematic review.

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.

Declining HIV infection rates among recently married primigravid women in Pune, India.

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.

Low sensitivity of total lymphocyte count as a surrogate marker to identify antepartum and postpartum Indian women who require antiretroviral therapy.

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.

Clinically significant anemia in HIV-infected pregnant women in India is not a major barrier to zidovudine use for prevention of maternal-to-child transmission.

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.