Design of the HIV Prevention Trials Network (HPTN) Protocol 054: A cluster randomized crossover trial to evaluate combined access to Nevirapine in developing countries

HPTN054 is a cluster randomized trial designed to compare two approaches to providing single dose nevirapine to HIV-seropositive mothers and their infants to prevent mother-to-child transmission of HIV in resource limited settings. A number of challenging issues arose during the design of this trial. Most importantly, the need to achieve high participation rates among pregnant, HIV-seropositive women in selected prenatal care clinics led us to develop a method of collecting anonymous and unlinked information on a key surrogate endpoint instead of pursuing linked and identified information on a clinical endpoint. In addition, since group counseling is the standard model for prenatal care in sub-Saharan Africa, the prenatal care clinic serves as the unit of randomization. However, constraints on the number of suitable clinics and other logistical difficulties necessitated a unique type of hybrid parallel/stepped wedge cluster randomized design in which some clinics cross over between the two treatment modalities and some do not. We describe the design for the HPTN054 trial with an emphasis on the logistic and statistical features that allowed us to address these issues. We also provide some general statistical results that are useful for computing power in parallel, crossover, stepped wedge or mixed designs of cluster randomized trials

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries

BACKGROUND: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. Methods and FINDINGS: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r  = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r  = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. CONCLUSIONS: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed. Please see later in the article for the Editors' Summar

HIV, infant feeding and more perils for poor people: new WHO guidelines encourage review of formula milk policies

The release of the new WHO guidelines on HIV and infant feeding, in a global context of widespread impoverishment, requires countries to re-examine their infant-feeding policies in relation to broader socioeconomic issues. This widening scope is necessitated by compelling new reports on the scale of global underdevelopment in developing countries. This paper explores these issues by addressing feeding choices made by HIV-infected mothers and programmes supplying free formula milks within a global environment of persistent poverty. Accumulating evidence on the increase in malnutrition, morbidity and mortality associated with the avoidance or early cessation of breastfeeding by HIV-infected mothers, and the unanticipated hazards of formula feeding, demand a deeper assessment of the measures necessary for optimum policies on infant and child nutrition and for the amelioration of poverty. Piecemeal interventions that increase resources directed at only a fraction of a family’s impoverishment, such as basic materials for preparation of hygienic formula feeds and making flawed decisions on choice of infant feeding, are bound to fail. These are not alternatives to taking fundamental steps to alleviate poverty. The economic opportunity costs of such programmes, the equity costs of providing resources to some and not others, and the leakages due to temptation to sell capital goods require careful evaluation. Providing formula to poor populations with high HIV prevalence cannot be justified by the evidence, by humanitarian considerations, by respect for local traditions or by economic outcomes. Exclusive breastfeeding, which is threatened by the HIV epidemic, remains an unfailing anchor of child survival

Education of children with human immunodeficiency virus infection

Treatment for human immunodeficiency virus (HIV) infection has enabled more children and youths to attend school and participate in school activities. Children and youths with HIV infection should receive the same education as those with other chronic illnesses

Identification and care of HIV-exposed and HIV-infected infants, children, and adolescents in foster care

As a consequence of the expanding human immunodeficiency virus (HIV) epidemic and major advances in medical management of HIV-exposed and HIV-infected persons, revised recommendations are provided for HIV testing of infants, children, and adolescents in foster care. Updated recommendations also are provided for the care of HIV-exposed and HIV-infected persons who are in foster care

Human immunodeficiency virus/acquired immunodeficiency syndrome education in schools

The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic has grown during the past 15 years. Education remains a critical component of our efforts to prevent HIV infection/AIDS in school children and young adults. To accomplish this goal, school personnel should receive updated information about HIV infection/AIDS so that accurate teaching on this topic can be included in the K-12 health education curriculum. Informed pediatricians and nurses can serve as important resources for school health services and administration to provide current information for the curriculum. Each community should have a school health advisory committee that enlists community support and provides input to health education programs in schools

Issues related to human immunodeficiency virus transmission in schools, child care, medical settings, the home, and community

Current recommendations of the American Academy of Pediatrics (AAP) for infection control practices to prevent transmission of blood-borne pathogens, including human immunodeficiency virus (HIV) in hospitals, other medical settings, schools, and child care facilities, are reviewed and explained. Hand-washing is essential, whether or not gloves are used, and gloves should be used when contact with blood or blood-containing body fluids may occur. In hospitalized children, the 1996 recommendations of the Centers for Disease Control and Prevention (CDC) should be implemented as modified in the 1997 Red Book. The generic principles of Standard Precautions in the CDC guidelines generally are applicable to children in all health care settings, schools, child care facilities, and the home. However, gloves are not required for routine changing of diapers or for wiping nasal secretions of children in most circumstances. This AAP recommendation differs from that in the CDC guidelines. Current US Public Health Service guidelines for the management of potential occupational exposures of health care workers to HIV are summarized. As previously recommended by the AAP, HIV-infected children should be admitted without restriction to child care centers and schools and allowed to participate in all activities to the extent that their health and other recommendations for management of contagious diseases permit. Because it is not required that the school be notified of HIV infection, it may be helpful if the pediatrician notify the school that he or she is operating under a policy of nondisclosure of infection with blood-borne pathogens. Thus, it is possible that the pediatrician will not report the presence of such infections on the form. Because HIV infection occurs in persons throughout the United States, these recommendations for prevention of HIV transmission should be applied universally