Louise Kuhn

Human Papillomavirus Infection in Women Infected with the Human Immunodeficiency Virus

Background Among women infected with the human immunodeficiency virus (HIV), there is a high prevalence of human papillomavirus (HPV) infections. However, little is known about the natural history of HPV infections in HIV-seropositive women, and persistent HPV infections may explain the increased risk of cervical squamous intraepithelial lesions and invasive cervical cancer in HIV-seropositive women. Methods A total of 220 HIV-seropositive and 231 HIV-seronegative women in the New York City area were evaluated at two or more semiannual gynecologic examinations that included a Pap test, a test for HPV DNA, and colposcopy. Results HPV DNA was detected at the initial examination in 56 percent of the HIV-seropositive and 31 percent of the HIV-seronegative women. After four examinations, the cumulative prevalence of HPV infection was 83 percent in the seropositive women and 62 percent in the seronegative women (P<0.001). Persistent HPV infections were found in 24 percent of the seropositive women but in only 4...

Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study

Summary Background The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixedfed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1. Methods We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test. Findings At 3 months, 18·8% (95% CI 12·6–24·9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21·3% (17·2–25·5) of 393 breastfed children (p=0·5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14·6% [7·7–21·4] vs 24·1% [19·0–29·2], p=0·03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0·52 [0·28–0·98]) and a similar risk to no breastfeeding (0·85 [0·51–1·42]). Interpretations Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding.

Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban South Africa.

ObjectiveTo determine the risk of HIV transmission by infant feeding modality. Design and settingA prospective study in two hospitals in Durban, South Africa. ParticipantsA total of 551 HIV-infected pregnant women enrolled in a randomized trial of vitamin A. InterventionsWomen self-selected to breastfeed or formula feed after being counselled. Breastfeeders were encouraged to practice exclusive breastfeeding for 3–6 months. Main outcome measuresCumulative probabilities of detecting HIV over time were estimated using Kaplan–Meier methods and were compared in three groups: 157 formula-fed (never breastfed); 118 exclusively breastfed for 3 months or more; and 276 mixed breastfed. ResultsThe three feeding groups did not differ in any risk factors for transmission, and the probability of detecting HIV at birth was similar. Cumulative probabilities of HIV detection remained similar among never and exclusive breastfeeders up to 6 months: 0.194 (95% CI 0.136–0.260) and 0.194 (95% CI 0.125–0.274), respectively, whereas the probabilities among mixed breastfeeders soon surpassed both groups reaching 0.261 (95% CI 0.205–0.319) by 6 months. By 15 months, the cumulative probability of HIV infection remained lower among those who exclusively breastfed for 3 months or more than among other breastfeeders (0.247 versus 0.359). ConclusionInfants exclusively breastfed for 3 months or more had no excess risk of HIV infection over 6 months than those never breastfed. These findings, if confirmed elsewhere, can influence public health policies on feeding choices available to HIV-infected mothers in developing countries.

Effects of early, abrupt weaning on HIV-free survival of children in Zambia.

BACKGROUND In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. METHODS We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. RESULTS In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). CONCLUSIONS Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)

Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child Hiv-1 transmission in Durban, South Africa

OBJECTIVE Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1. DESIGN AND METHODS In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age. RESULTS There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8). CONCLUSION Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.

Evaluation of alternative methods of cervical cancer screening for resource‐poor settings

Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource‐poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality.

Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study.

BACKGROUND Bacterial vaginosis (BV) may increase womens susceptibility to HIV infection, but there are few prospective data. METHODS During follow-up for up to 36 months, 86 new HIV seroconverters (case patients) were identified among 5110 women enrolled in a cervical cancer screening trial. Nonseroconverting control subjects (n=324) were frequency matched to case patients by age and duration of follow-up. At enrollment, case patients and control subjects were evaluated for clinical signs of BV, and Gram stains of vaginal fluid were scored using Nugent criteria. RESULTS BV was diagnosed on the basis of clinical criteria at enrollment in 20% of seroconverters and 16% of control subjects (summary odds ratio [OR], 1.31 [95% confidence interval {CI}, 0.71-2.41]). Nugent criteria for BV were met by 74% of seroconverters and 62% of control subjects. Diagnosis of BV on the basis of Nugent criteria was significantly associated with an increased risk of HIV seroconversion, after adjustment for demographic characteristics, other sexually transmitted infections, and sexual behaviors (adjusted OR, 2.01 [95% CI, 1.12-3.62]). CONCLUSIONS BV may account for a substantial fraction of new HIV infections in this setting. Treatment of BV and other interventions to promote normal vaginal flora warrant attention for HIV prevention.

Low-income neighborhoods and the risk of severe pediatric injury: a small-area analysis in northern Manhattan.

OBJECTIVES The purpose of this study was to investigate the relationship between socioeconomic disadvantage and the incidence of severe childhood injury. METHODS Small-area analysis was used to examine socioeconomic risk factors for pediatric injury resulting in hospitalization or death in Northern Manhattan, New York, NY, during a 9-year period (1983 through 1991). RESULTS The average annual incidence of all causes of severe pediatric injury was 72.5 per 10,000 children; the case-fatality rate was 2.6%. Census tract proportions of low-income households, single-parent families, non-high school graduates, and unemployment were significant predictors of risk for both unintentional and intentional injury. Among the socioeconomic factors considered, low income was the single most important predictor of all injuries; other socioeconomic variables were not independent contributors once income was included in the model. Compared with children living in areas with few low-income households, children in areas with predominantly low-income households were more than twice as likely to receive injuries from all causes and four and one half times as likely to receive assault injuries. The effect of neighborhood income disparities on injury risk persisted after race was controlled. CONCLUSIONS These results illuminate the impact of socioeconomic disparities on child health and point to the need for injury prevention efforts targeting low-income neighborhoods.

Direct visual inspection for cervical cancer screening : an analysis of factors influencing test performance

The authors evaluated direct visual inspection of the cervix after the application of 5% acetic acid (DVI) as a cervical cancer screening test for use in low‐resource settings.

T-helper cell responses to HIV envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission.

BackgroundAcquired HIV-specific cell-mediated immune responses have been observed in exposed–uninfected individuals, and it has been inferred, but not demonstrated, that these responses constitute a part of natural protective immunity to HIV. This inference was tested prospectively in the natural exposure setting of maternal–infant HIV transmission in a predominantly breast-fed population. MethodsCord blood from infants of HIV-seropositive women in Durban, South Africa, were tested for in vitro reactivity to a cocktail of HIV envelope peptides (Env) using a bioassay measuring interleukin-2 production in a murine cell line. Infants were followed with repeat HIV RNA tests up to 18 months of age to establish which ones acquired HIV-infection. ResultsT-helper cell responses to Env were detected in 33 out of 86 (38%) cord blood samples from infants of HIV-seropositive women and in none of nine samples from seronegative women (P = 0.02). Among infants of HIV-seropositive mothers, three out of 33 with T-helper responses to Env were already infected before delivery (HIV RNA positive on the day of birth), two were lost to follow-up, and none of the others (out of 28) were found to be HIV infected on subsequent tests. In comparison, six out of 53 infants unresponsive to Env were infected before delivery, and eight out of 47 (17%) of the others were found to have acquired HIV infection intrapartum or post-partum through breast-feeding (P = 0.02). ConclusionsT-helper cell responses to HIV envelope peptides were detected in more than one-third of newborns of HIV-infected women; no new infections were acquired by these infants at the time of delivery or post-natally through breast-feeding if these T-helper cell responses were detected in cord blood.