Sandesh Patil

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.

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 ≥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 infants 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

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.

Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune India but is not associated with mother-to-child HIV transmission.

Abstract A recent report from Tanzania demonstrated an increased risk of being HIV infected or of dying at birth among children born to breastfeeding mothers with low baseline vitamin D levels. We conducted a nested case-control study among HIV-infected pregnant women in western India to confirm the association between maternal vitamin D levels and mother-to-child transmission (MTCT) of HIV. Vitamin D insufficiency and deficiency were common among HIV-infected pregnant women, but were not associated with mother to child HIV transmission at 1 year postpartum (adjusted odds ratio [AOR], 0.66; 95% CI, 0.30-1.45; P = .30).

Soluble CD14: An Independent Biomarker for the Risk of Mother-to-Child Transmission of HIV in a Setting of Preexposure and Postexposure Antiretroviral Prophylaxis

Elevated soluble CD14 (sCD14) concentrations, a marker of monocyte activation, predicts adverse outcomes in human immunodeficiency virus (HIV)-infected adults. To examine the association of sCD14 concentrations with the risk of mother-to-child transmission (MTCT) of HIV, we nested a case-control study (49 pairs of infants and their HIV-infected mothers) within the Six-Week Extended-Dose Nevirapine trial. Median peripartum maternal log2 sCD14 concentration was higher among transmitters (defined as pairs in which maternally transmitted HIV infection occurred by 12 months of age) than nontransmitters (20.29 pg/mL vs 19.41 pg/mL; P = .005). There was an increased odds of MTCT for every log2 increase in maternal sCD14 concentration, after adjustment for maternal HIV load, CD4 count and cART exposure (adjusted odds ratio, 3.51; 95% confidence interval, 1.21-10.21). Maternal monocyte activation may adversely influence the risk of MTCT of HIV.

Maternal Syphilis: An Independent Risk Factor for Mother to Infant Human Immunodeficiency Virus Transmission

Abstract Syphilis is associated with increased human immunodeficiency virus acquisition and sexual transmission; we examined impact on human immunodeficiency virus mother-to-child transmission among mother-infant pairs enrolled in the India Six-Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically using Venereal Disease Research Laboratory titer plus Treponema Pallidum Hemagglutination Assay, was associated with 2.5-fold greater risk.

Contraceptive Use and Factors Associated With Postpartum Surgical Sterilization Among HIV-Infected Women in Pune, India

The authors desire to better understand contraceptive practices and factors associated with surgical tubal ligation (STL) among HIV-infected women. Secondary data were obtained from HIV-infected women enrolled in a National Institutes of Health–funded clinical trial assessing the efficacy of extended-dose nevirapine given to breastfed infants at a government hospital in Pune, India, and were analyzed. The most common contraceptive methods adopted were abstinence (55%), followed by STL (34%). Having a living male child and being multigravida were directly associated with acceptance of STL. Thorough contraceptive counseling services are needed for HIV-infected women so that STL is not perceived to be protective against sexually transmitted diseases and HIV transmission.