Assessing the effects of a complementary parent intervention and prior exposure to a preadolescent program of HIV risk reduction for mid-adolescents.

OBJECTIVES: We (1) evaluated the impact of an evidence-based HIV prevention program with and without a parent component among mid-adolescents living in the Caribbean and (2) determined the effect of prior receipt of a related intervention during preadolescence on intervention response. METHODS: A randomized, controlled 4-cell trial of a 10-session, theory-based HIV prevention intervention involving 2564 Bahamian grade-10 youths (some of whom had received a comparable intervention in grade 6) was conducted (2008-2011). Randomization occurred at the level of the classroom with follow-up at 6, 12, and 18 months after intervention. The 3 experimental conditions all included the youths' curriculum and either a youth-parent intervention emphasizing adolescent-parent communication, a parent-only goal-setting intervention, or no parent intervention. RESULTS: An intervention delivered to mid-adolescents in combination with a parent-adolescent sexual-risk communication intervention increased HIV/AIDS knowledge, condom-use skills, and self-efficacy and had a marginal effect on consistent condom use. Regardless of prior exposure to a similar intervention as preadolescents, youths benefited from receipt of the intervention. CONCLUSIONS: Preadolescents and mid-adolescents in HIV-affected countries should receive HIV prevention interventions that include parental participation.

Developmental implications of HIV prevention during adolescence: Examination of the long-term impact of HIV prevention interventions delivered in randomized controlled trials in grade six and in grade 10.

Dramatic changes occur in abstract reasoning, physical maturation, familial relationships and risk exposure during adolescence. It is probable that delivery of behavioral interventions addressing decision-making during the pre-adolescent period and later in adolescence would result in different impacts. We evaluated the intervention effects of an HIV prevention program (Bahamian Focus on Older Youth, BFOOY) administered to grade 10 Bahamian youth and parents to target HIV protective and risk behaviors. We also examined the effects of prior exposure to a similar intervention (Focus on Youth in the Caribbean, FOYC) four years earlier. At six months post-intervention, receipt of BFOOY by youth unexposed to FOYC increased HIV knowledge and condom-use skills. Differences based on BFOOY exposure were not present among FOYC-exposed youth, whose knowledge and condom-use skills were already higher than those of unexposed youth. Youth receiving both interventions displayed a carryover effect from FOYC, demonstrating the highest scores six months post-intervention.

Development of Condom-Use Self-Efficacy over 36 months among Early Adolescents: A Mediation Analysis.

This research evaluates condom-use self-efficacy and its increase throughout adolescence. Documentation of the development of condom-use self-efficacy would be important for prevention efforts given the influence of self-efficacy on actual condom-usage. This study assesses a hypothesized mediation mechanism of the development of self-efficacy using a mediation analysis approach. The participants, 497 grade-6 Bahamian students, were randomly assigned to the control condition in a 3-year longitudinal HIV prevention program trial. Condom-use self-efficacy consistently increased and condom-use self-efficacy assessed at earlier periods was positively associated with its values at subsequent periods. Additionally, self-efficacy assessed between two time points one year apart or longer (e.g., 6 months between baseline and 12 months) significantly mediated the impact of its levels at the previous assessment on the level at the subsequent assessment. To sustain program effect, HIV prevention programs should strive to enhance self-efficacy and provide reinforcing "boosters" no later than 12 months post-intervention.

Multi-year school-based implementation and student outcomes of an evidence-based risk reduction intervention.

BACKGROUND: Intervention effects observed in efficacy trials are rarely replicated when the interventions are broadly disseminated, underscoring the need for more information about factors influencing real-life implementation and program impact. Using data from the ongoing national implementation of an evidence-based HIV prevention program [Focus on Youth in The Caribbean (FOYC)] in The Bahamas, this study examines factors influencing teachers' patterns of implementation, the impact of teachers' initial implementation of FOYC, and subsequent delivery of the booster sessions on students' outcomes. METHODS: Data were collected from the 80 government elementary and 34 middle schools between 2011 and 2014, involving 208 grade 6, 75 grade 7, and 58 grade 8 teachers and 4411 students initially in grade 6 and followed for 3 years. Student outcomes include HIV/AIDS knowledge, reproductive health skills, self-efficacy, and intention to use protection. Data from teachers includes implementation and modification of the curriculum, attitudes towards the prevention program, comfort level with the curriculum, and attendance at training workshops. Structural equation modeling and mixed-effect modeling analyses were applied to examine the impact of teachers' implementation. RESULTS: Teachers' attitudes towards and comfort with the intervention curriculum, and attendance at the curriculum training workshop had a direct effect on teachers' patterns of implementation, which had a direct effect on student outcomes. Teachers' attitudes had a direct positive effect on student outcomes. Teachers' training in interactive teaching methods and longer duration as teachers were positively associated with teachers' comfort with the curriculum. High-quality implementation in grade 6 was significantly related to student outcomes in grades 6 and 7 post-implementation. Level of implementation of the booster sessions in grades 7 and 8 were likewise significantly related to subsequent student outcomes in both grades. CONCLUSIONS: High-quality initial implementation of a prevention program is significantly related to better program outcomes. Poor subsequent delivery of booster sessions can undermine the positive effects from the initial implementation while strong subsequent delivery of booster sessions can partially overcome poor initial implementation.

Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.

BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. SUBJECTS: The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. METHODS: One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/m(2) or 300/75 mg/m(2) lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. RESULTS: All subjects were escalated to the 300/75 mg/m(2) twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/ml at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/mm(3); 10.3%) and ARV-experienced subjects (284 cells/mm(3); 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. CONCLUSIONS: The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.

High-risk cervical human papillomavirus infections among human immunodeficiency virus-positive women in the Bahamas.

BACKGROUND: High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women. METHODS: One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients. RESULTS: Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value  = 0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200. CONCLUSIONS: HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women.

Adolescent age at time of receipt of one or more sexual risk reduction interventions.

PURPOSE: Age of the target audience at time of intervention is thought to be a critical variable influencing the effectiveness of adolescent sexual risk reduction interventions. Despite this postulated importance, to date, studies have not been designed to enable a direct comparison of outcomes according to age at the time of intervention delivery. METHODS: We examined outcomes of 598 youth who were sequentially involved in two randomized controlled trials of sexual risk prevention interventions, the first one delivered in grade 6 (Focus on Youth in the Caribbean [FOYC]) and the second one in grade 10 (Bahamian Focus on Older Youth [BFOOY]). Four groups were examined, including those who received (1) both treatment conditions, FOYC and BFOOY; (2) FOYC in grade 6 and the control condition in grade 10; (3) the control condition in grade 6 and BFOOY in grade 10; and (4) both control conditions. Intentions, perceptions, condom-use skills, and HIV-related knowledge were assessed over 60 months. RESULTS: Data showed that those who received both interventions had the greatest increase in condom-use skills. Youth who received FOYC in grade 6 had greater scores in knowledge and intention. CONCLUSION: These results suggest that youth receive the most protection with early and repeated exposure to interventions. These findings suggest that educators should consider implementing HIV prevention and risk reduction programs as a fixed component of education curriculum beginning in the preadolescent years and if possible also during the adolescent years.

Effect of a grade 6 HIV risk reduction intervention four years later among students who were and were not enrolled in the study trial.

PURPOSE: To assess the long-term impact of HIV-prevention interventions delivered to youth before sexual initiation and the effects of interventions delivered in nonstudy settings. METHODS: A five-group comparison of HIV knowledge, and condom-use skills, self-efficacy, intentions, and practice among 1,997 grade 10 students attending one of the eight government high schools in Nassau, The Bahamas. Group 1 received an HIV-prevention intervention, Focus on Youth in the Caribbean (FOYC), in grade 6 as part of a randomized trial; group 2 received FOYC as part of the regular school curriculum but outside of the trial; group 3 received the control condition as part of the trial; group 4 received the control condition as part of the school curriculum but outside of the trial; and individuals in group 5 (naive controls) were not enrolled in a school receiving FOYC or the control conditon and did not participate in the trial. RESULTS: FOYC youth compared with the control youth and naive controls had higher HIV knowledge, condom-use skills, and self-efficacy 4 years later. By subgroups, group 1 demonstrated higher HIV/AIDS knowledge than all groups except group 2, higher condom skills than all groups, and higher condom self-efficacy than Naive Controls. Youth in group 2 demonstrated higher HIV knowledge than youth in groups 3-5. Behavioral effects were not found. CONCLUSIONS: FOYC delivered to grade 6 students continued to have protective effects 4 years later. Positive effects are present among youth who received FOYC as part of the school curriculum but were not enrolled in the trial.

When things are not as they appear: assessing the adequacy of cluster randomization when outcome events are rare at baseline.

The present study randomly assigned 15 Bahamian elementary schools to one of three intervention conditions. To assess the adequacy of cluster randomization, we examined two concerns identified by the local research team: inequality of gender distribution and environmental risk among groups. Baseline significant differences in risk and protective behaviors were minimal. There were significantly more males in the intervention group. Males had higher rates of risk behavior at all assessments. Poor school performance was also higher among the intervention condition and was significantly associated with increased rates of many but not all risk behaviors. Prior to adjusting for gender and school performance, several risk behaviors appeared to be higher after intervention among intervention youth. Adjusting for gender and school performance eradicated the group differences in risk behavior rates. Results demonstrate the importance of adequate randomization where outcomes of interest are rare events at baseline or differ by gender and there is an unequal gender distribution and the importance of the local research team's knowledge of potential inequalities in environmental risk (i.e., school performance). Not considering such individual differences could impact the integrity of trial outcomes.

Focus on youth in the Caribbean: beyond the numbers.

In the 1990s, an interdisciplinary group including pediatricians, anthropologists, health educators, psychologists, and statisticians developed and evaluated an HIV prevention intervention targeting early adolescents living in public housing developments in the USA. The intervention, "Focus on Kids," (FOK) was effective in reducing risk behaviors, intentions, and perceptions and ultimately was included in the Center for Disease Control's portfolio of effective adolescent programs, "Programs that Work." Learning about FOK and concerned about the need for a structured program to address high rates of teen pregnancy and risk for HIV, professionals from the Ministries of Health of The Bahamas approached the researchers about collaborating to develop a program for Bahamian youth. A partnership developed which has spanned over a decade and led to the development of an intervention program targeting Bahamian children in grade six, a 10-session adolescent HIV prevention program entitled "Focus on Youth in the Caribbean" (FOYC). Two programs including a video and parent discussion were developed for their parents. Caribbean Informed Parents and Children Together (CImPACT) emphasizes the importance of parent-child communication about sexuality and "Goal for It" (GFI) emphasizes the importance of planning ahead. The US-Bahamian team evaluated these interventions through a randomized, controlled 3-celled longitudinal trial (36 months follow-up) involving 15 elementary schools in The Bahamas. The programs have been shown to be effective. This article describes the context in which the epidemic occurred, events leading up to the collaboration and the issues, decisions, processes, and relationships that we have developed that have allowed it to succeed.

The prevalence of cervical cytology abnormalities and human papillomavirus in women infected with the human immunodeficiency virus.

INTRODUCTION: The human papillomavirus (HPV) is the major etiologic agent in the development of cervical cancer and its natural history of infection is altered in persons infected with the human immunodeficiency virus (HIV). The prevalence of HPV infection and cervical dysplasia in the HIV sero-positive females in the Bahamas is not known. Finding out the prevalence would allow for the establishment of protocols to optimize total care of this population and help prevent morbidity and mortality related to cervical cancer. OBJECTIVE: The Objective of this study is to determine the prevalence of high risk HPV genotypes and the prevalence of cervical dysplasia in the HIV sero-positive females attending the Infectious Disease Clinic at the Princess Margaret Hospital, Nassau, Bahamas. METHODS: One hundred consecutive, consenting, non-pregnant, HIV-sero-positive females from the Infectious Disease Clinic at the Princess Margaret Hospital in Nassau, Bahamas were screened for high-risk HPV infections and cervical cytology abnormalities using liquid-based pap smear and signal amplification nucleic acid method for HPV detection. A questionnaire was also utilized to gather demographic information and obtain information on known risk factors associated with HPV infections such numbers of partners. RESULTS: The prevalence of high-risk HPV was 67% and cervical abnormalities were noted in 44% of the study population. High-risk HPV types were more likely to be present in women with CD4+ cell counts less than 400 microl-1 and in women with cervical cytology abnormalities (97%). The most common cervical abnormality was low-grade squamous intraepithelial lesions. CONCLUSION: Findings suggest that HIV-sero positive females should have HPV testing done as part of their normal gynecology evaluation and these patients should be encouraged and provisions be made for ease of access having regular PAP smears and HPV testing.

Influence of host factors on immunoglobulin G concentration in oral fluid specimens.

The influence of host factors (tobacco use, dentition, bleeding gums, oral rinsing, nasal medications, and time since the last meal) on immunoglobulin G (IgG) concentration in oral fluids (OF) was determined by univariate and multivariate analysis. Significant differences in IgG concentration were found to be associated with human immunodeficiency virus (HIV) status (HIV antibody positive, +16.60 microg/ml, P = 0.0001), sex (female, +1.23 microg/ml, P = 0.004), dentition (+2.83 microg/ml, edentulous versus dentulous, P = 0.0001), bleeding gums (+6.35 microg/ml, P = 0.0001), and time since the last meal (+3.55 microg/ml, >6 h, P = 0.0001). These factors could impact diagnostic methods that rely on the immunoglobulin concentration in OF specimens.

Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody

The VIDAS HIV DUO Ultra, a fourth-generation immunoassay under development for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 and HIV-2, was evaluated. The enzyme-linked fluorescence immunoassay, performed on the automated VIDAS instrument, is claimed to detect early and established HIV infection. The assay was challenged with a total of 2,847 samples that included 74 members of 10 seroconversion panels, 9 p24 antigen-only-reactive members of a panel of group M clades, 503 consecutively collected samples from individuals seeking care in the University of Maryland Medical System, 1,010 samples from U.S. blood donors, 1,141 samples from patients in a high-incidence population in Trinidad, 83 samples from a clinic for sexually transmitted diseases in the Bahamas, 10 confirmed HIV-1 group O samples, and 16 confirmed HIV-2 samples from the Cote d'Ivoire. Reference tests were U.S. Food and Drug Administration-licensed HIV antibody screening, p24 antigen tests, HIV confirmatory assays, and the Roche Diagnostics Amplicor HIV-1 Monitor. The VIDAS HIV DUO Ultra demonstrated 100% sensitivity and 99.5% specificity overall, with a 99.7% specificity in low-risk individuals. The analytical sensitivity, as assessed by seroconversion panels and p24 antigen in samples, was equivalent to the sensitivity of the reference assays used to characterize these panels. The VIDAS HIV DUO Ultra is accurate, offers potential advantages over conventional HIV testing for time and cost savings, has walk-away capability, and correctly identifies both early and established HIV infections.

Dried blood spots collected on filter paper: an international resource for the diagnosis and genetic characterization of human immunodeficiency virus type-1

The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.

A multidisciplinary approach to scaling up HIV/AIDS treatment and care: the experience of the Bahamas

The Bahamas has a total population of 314,000. It is estimated that there are now 5,600 to 8,700 adults and children living with HIV/AIDS in the country. Approximately 2,500 women in the age range of 15 to 49 years are infected with HIV. To address the HIV/AIDS epidemic, the Bahamas has developed effective HIV/AIDS prevention, care, and treatment policies that have been applied since 1985. The Bahamas National AIDS Program has developed strategies and interventions in the areas of prevention and education, comprehensive care (clinical and social interventions), support services, and surveillance and researc (clinical and behavioral) (AU)