Can community health workers improve adherence to highly active antiretroviral therapy in the USA? A review of the literature.

OBJECTIVES: Highly active antiretroviral therapy (HAART) has transformed HIV infection into a manageable chronic illness, yet AIDS mortality among ethnic minorities persists in the USA. HAART nonadherence is associated with increased HIV viral load, low CD4 cell count and racial disparities in HIV outcomes. While there is no universal consensus on how to improve medical adherence in HIV-positive populations, the community health worker (CHW) model is emerging as an effective strategy to overcome barriers to HAART adherence. Although utilized in international settings, there is little evidence regarding the effects of CHWs on HIV outcomes in the USA. METHODS: We performed a comprehensive search from May 2010 to November 2010 to identify studies carried out in the USA that utilized CHWs to improve HAART adherence and measured HIV viral loads and CD4 cell counts to assess intervention effects. Sixteen studies met the inclusion criteria and were reviewed for this article. All studies reported clinical HIV outcomes. RESULTS: Interventions that lasted at least 24 weeks, provided frequent contact with participants, and focused on medication management were associated with improved HAART adherence, as indicated by reduced HIV viral load and increased CD4 cell count. CONCLUSIONS: Compared with current standards of care, CHW programmes may offer a practical and cost-effective alternative to improve HAART adherence, which may lead to reduced HIV viral load and increased CD4 cell counts among HIV-positive populations in the USA.

Caregivers' perception of HIV-infected Dominican children's behaviour.

Caregivers (mothers and non-mothers) of HIV children face many challenges related to both physical demands and emotional well-being. The perception of caregivers in the Dominican Republic, a country greatly impacted by HIV/AIDS, in regard to their children's behaviour, has not been investigated to date. To extend understanding of the potential behavioural issues involved in providing care to children without access to antiretroviral therapy, the Child Behaviour Checklist was administered to 52 caregivers of HIV Dominican children (2-8 years old). Both mothers and non-mothers perceived significant pathological internalizing behavioural symptoms in immunosuppressed children, compared to children with less disease progression. Analyses of gender comparisons revealed that older female children were perceived as withdrawn/depressed by their caregivers. These findings suggest that children's disease status may be an important contributor to caregiver perception in mothers, as well as non-mothers and indicate that gender-specific relationships warrant further study.

Behavioural symptoms of children with HIV infection living in the Dominican Republic.

OBJECTIVE: The purpose of this report is to describe behavioural problems encountered in a group of Dominican children living with Human Immunodeficency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in the Dominican Republic. They were not receiving antiretroviral treatment. METHOD: The participants were 43 children with HIV infection (2 to 8 years of age) who were attending an immunology clinic in the largest paediatric hospital in the Dominican Republic. All of the participants were vertically infected with the HIV virus (mother-to-child transmission) and had a very low socio-economic status. The children's caregivers were administered the Child Behavioural Checklist (CBCL) by trained psychologists to determine the caregivers 'perception of the children's behavioural problems. Behavioural findings were examined according to the CBCL age format: younger children (under 5 years of age) and older children (over 6 years of age). RESULTS: Descriptive statistics revealed a high proportion of the children, both younger (approximately 40%) and older (46%) scored in the borderline/clinical ranges for internalizing problems, including anxiety, withdrawn-depressed and somatic complaints. In addition, 46% of the older children were perceived as having externalizing problems (rule breaking and aggressive behaviour). CONCLUSION: These findings suggest that a high incidence of behavioural and mood problems may be prevalent among Dominican children with HIV Thefindings are discussed in terms of future research to examine other risk factors that might contribute to the high rate of maladaptive behaviours observed in the present report, including the contribution of socio-economic status, caregiver illness, caregiver education and parental loss.

Caregivers' perception of HIV-infected Dominican children's behaviour / La percepción de los encargados del cuidado de la salud en relación con la Conducta de niños dominicanos infestados por vih

Caregivers (mothers and non-mothers) of HIV children face many challenges related to both physical demands and emotional well-being. The perception of caregivers in the Dominican Republic, a country greatly impacted by HIV/AIDS, in regard to their children's behaviour, has not been investigated to date. To extend understanding of the potential behavioural issues involved in providing care to children without access to antiretroviral therapy, the Child Behaviour Checklist was administered to 52 caregivers of HIV Dominican children (2-8 years old). Both mothers and non-mothers perceived significant pathological internalizing behavioural symptoms in immunosuppressed children, compared to children with less disease progression. Analyses of gender comparisons revealed that older female children were perceived as withdrawn/depressed by their caregivers. These findings suggest that children's disease status may be an important contributor to caregiver perception in mothers, as well as non-mothers and indicate that gender-specific relationships warrant further study.

Los encargados del cuidado de la salud (madres y no madres) de niños HIV+ enfrentan muchos retos, tanto en relación con las exigencias físicas cuanto con respecto al estado emocional de los niños. La percepción de los encargados del cuidado de la salud en República Dominicana ­ un país muy impactado por el VIH/SIDA ­ con respecto a la conducta de sus niños, no se ha investigado hasta hoy. A fin de extender la comprensión de los problemas potenciales de comportamiento implícitos en ofrecer cuidado a niños sin acceso a terapia antiretroviral, se administró la Lista de Conductas Infantiles ­ conocida en inglés como Chile Behaviour Checklist ­ a los encargados del cuidado de la salud de los niños dominicanos VIH+ (2 ­ 8 años de edad). Tanto las madres como las no madres percibieron síntomas significativos de conducta de interiorización patológica en los niños inmunodeprimidos, en comparación con los niños con la enfermedad menos avanzada. Los análisis de las comparaciones de género revelaron que las niñas de más edad, pero no los varones, eran percibidas como retraídas/ deprimidas por los encargados del cuidado. Estos hallazgos sugieren que el estatus de la enfermedad de los niños, puede ser un factor que contribuye de forma importante a la percepción de los encargados del cuidado de la salud, ya sean o no madres, e indioan que las relaciones específicas de género merece más estudio

Behavioural symptoms of children with HIV infection living in the Dominican Republic / Síntomas de conducta de los niños infectados por vih en la república dominicana

OBJECTIVE: The purpose of this report is to describe behavioural problems encountered in a group of Dominican children living with Human Immunodeficency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in the Dominican Republic. They were not receiving antiretroviral treatment. METHOD: The participants were 43 children with HIV infection (2 to 8 years of age) who were attending an immunology clinic in the largest paediatric hospital in the Dominican Republic. All of the participants were vertically infected with the HIV virus (mother-to-child transmission) and had a very low socio-economic status. The children's caregivers were administered the Child Behavioural Checklist (CBCL) by trained psychologists to determine the caregivers 'perception of the children's behavioural problems. Behavioural findings were examined according to the CBCL age format: younger children (under 5 years of age) and older children (over 6 years of age). RESULTS: Descriptive statistics revealed a high proportion of the children, both younger (approximately 40) and older (46) scored in the borderline/clinical ranges for internalizing problems, including anxiety, withdrawn-depressed and somatic complaints. In addition, 46of the older children were perceived as having externalizing problems (rule breaking and aggressive behaviour). CONCLUSION: These findings suggest that a high incidence of behavioural and mood problems may be prevalent among Dominican children with HIV Thefindings are discussed in terms of future research to examine other risk factors that might contribute to the high rate of maladaptive behaviours observed in the present report, including the contribution of socio-economic status, caregiver illness, caregiver education and parental loss.

Objetivo. El propósito de este reporte es describir los problemas conductuales hallados en un grupo de niños dominicanos que viven con el virus de la inmunodeficiencia humana/síndrome de la inmunodeficiencia humana adquirida (VIH/AIDS) en República Dominicana, sin recibir tratamiento antiretroviral. Método. Los participantes fueron 43 niños (de 2 a 8 años de edad) infectados por el VIH, que asistían a una clínica inmunológica en el mayor hospital pediátrico de la República Dominicana. Todos los participantes estaban verticalmente infectados por el virus del VIH (transmisión de madre a hijo), y tenían un estatus socioeconómico bajo. Con el propósito de determinar la percepción que los encargados del cuidado de los niños tenían de los problemas conductuales de estos, psicólogos profesionales aplicaron a los cuidadores infantiles el instrumento conocido como la Lista de Control de la Conducta del Niño (CBCL). Los hallazgos conductuales fueron examinados de conformidad con el formato de edad de la CBCL: niños menores (por debajo de los 5 años de edad) y niños mayores (más de 6 años de edad) Resultados. Las estadísticas descriptivas revelaron que una alta proporción de niños, tanto menores (aproximadamente 40%) como mayores (46%), alcanzaron puntuaciones en los rangos clínicos/límites de problemas de internalización, incluyendo ansiedad, depresión con retraimiento, y quejas somáticas. Además, del 46% de los niños mayores se tuvo la percepción de que tenían problemas de externalización (rompimiento de las reglas y comportamiento agresivo). Conclusión. Estos hallazgos sugieren que prevalece una alta incidencia de problemas conductuales y anímicos entre los niños dominicanos con VIH. Los hallazgos se discuten en término de una investigación futura a fin de examinar otros factores de riesgo que podrían estar contribuyendo a la alta tasa de comportamientos maladaptativos observados en el reporte presente, incluyendo la contribución del estatus socioeconómico, la enfermedad de los propios cuidadores, la educación de los cuidadores y la pérdida de los padres.

Development of thrombocytosis in HIV+ drug users: impact of antiretroviral therapy.

With the exception of hemolytic anemia, the potential hematological toxicity of antiretrovirals (ARV) and combination treatments in HIV treated individuals has not been well established. We report, for the first time, hematological toxicity defined as thrombocytosis in 9% of the HIV+ patients receiving highly active antiretroviral treatment (HAART) being followed in a nutritional clinical trial. Participants were evaluated every 6 months during a 2-year period (1998-2000) and blood drawn for biochemical, hematological and immunological parameters. NK cells were negatively correlated with platelet counts in the total cohort (P = 0.018) and persistently elevated with ARVT. Chronic thrombocytosis was associated with significantly lower NK percentages (P = 0.005). Twenty-five percent of the patients with thrombocytosis developed a cardiovascular disease. Together, these results support the proposal that HAART may increase the risk of hematological dysfunction and impact the risk of cardiovascular disease.

High-risk behaviours in men from Bogotá, Colombia and the spread of HIV.

Our objective was to identify sexual behaviours related to risk of HIV infection. A cluster survey of sexually experienced men from diverse sociodemographic settings in Bogotá, Colombia was carried out using a standardized self-administered questionnaire. A high response rate (96%) resulted in the enrollment of 553 men. Most participants 129/442 reported having intercourse with women and 51/111 reported having sex with other men. Most respondents (90%) engaged in high-risk sexual practices; only 2% knew their HIV-1 serostatus. Consistent condom use was reported by 20% of those who practised anal sex, and was even lower (5%) among men who had sex with women during menses. Heterosexuals exhibited a higher degree of risky sexual patterns than homosexual/bisexuals (P=0.01). In conclusion, high-risk sexual practices are prevalent among men in Bogotá, particularly heterosexuals, attesting to the urgent need for effective and specific interventions to prevent HIV transmission.

Plasma zinc, copper, copper:zinc ratio, and survival in a cohort of HIV-1-infected homosexual men.

A prospective cohort study of 121 HIV-1-positive homosexual men was conducted in Miami, Florida, U.S.A. to evaluate the associations between plasma zinc and copper levels and mortality. Plasma zinc and copper levels were measured at baseline and then at semiannual visits. Zinc inadequacy and copper inadequacy were defined as plasma zinc levels <75 (microg/dl) and plasma copper levels <85 (microg/dl), respectively. HIV-1-related deaths were confirmed by review of death certificates. Cox proportional hazards regression models with time-dependent covariates were used to estimate the relative risks of zinc and copper inadequacy on mortality. Over the average course of the 3.3-year follow-up, 19 participants (16%) died of HIV-1-related causes. After adjustment for potential confounders, including low CD4+ cell counts and antiretroviral therapy, zinc inadequacy and copper:zinc ratio >1 (i.e., plasma copper level greater than plasma zinc level) were associated with increased mortality (relative risks [RRs]; 95% confidence intervals [CIs], 4.98, 1.30-19.00 and 8.28, 1.03-66.58, respectively). A negative association was also observed between plasma zinc levels and mortality (RR 0.94; 95% CI, 0.91-0.98). Plasma levels of copper were not significantly associated with mortality. These results suggest that plasma zinc inadequacy or the plasma copper:zinc ratio may be useful predictors of survival in HIV-1 infection. The latter appears to be a stronger predictor.

Randomized trial of supplemental beta-carotene to prevent second head and neck cancer.

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

Thrombocytopenia in HIV-infected drug users in the HAART era.

The present case-control study compared 26 HIV+ drug users having persistent thrombocytopenia (TCP<150 000/mm(3)) with 54 available age, gender and HIV CDC classification matched controls with normal platelet counts. Participants were followed longitudinally over a 2-year period (1998-2000), and hematological alterations evaluated in relationship to antiretroviral treatment, drug use and nutritional (selenium) status. Demographic information and medical history, including antiretroviral treatment were obtained. Blood was drawn for complete cell blood count, T lymphocytes and viral load. Sixty-nine percent of the individuals with persistent TCP and 49% of the controls were receiving antiretrovirals. At baseline, no significant differences in CD4 existed between the two groups. Over time, CD4 cell count declined in the cases (P = 0.05) and a significantly higher proportion of the cases (38%) developed AIDS (CD4<200 cell/mm(3)), as compared to the controls (18%, P = 0.004). A high risk for development of thrombocytopenia was observed with specific drug use (heroin 2.96 times, P = 0.0007), selenium levels below 145 microg/l (6 times, P = 0.008), and abnormal liver enzyme (SGOT) levels (2 times, P = 0.002). Together, these results indicate a number of factors that may be sensitive predictors of thrombocytopenia, which, despite antiretroviral treatment, appears to be related to more rapid disease progression in drug users.

Cognitive function in HIV-1-infected drug users.

Loss of cognitive ability, the most common neuropsychological complication in HIV-1 disease, may influence compliance with treatment and has been associated with decreased functional capacity, as well as an increased risk of mortality. In HIV-1-infected drug users, cognitive impairment affecting attention, memory, planning of complex tasks, information processing, and motor processes, has been reported, similar to findings in predominantly HIV-1-infected nondrug-using cohorts. The issue of whether early signs of cognitive dysfunction can be identified in asymptomatic HIV-1-infected drug users remains controversial. Evaluation of potential confounding factors, such as drug abuse, age, education, nutritional status, which may influence cognitive function, is essential for determining the dominant cause of neuropsychological abnormalities. There is evidence for a time-limited, protective effect against the development of AIDS dementia with zidovudine therapy. The potential ability of other therapies (e.g., antioxidants, B-complex vitamins) to prevent neuronal damage and protect the brain remains to be determined.

HIV-related high risk sexual behaviors and practices among women in Bogotá, Colombia.

Determinants associated with high-risk sexual behaviors were investigated in 1,133 sexually active women in Bogotá, Colombia. A self-administered questionnaire was completed by two groups of women: 721 representing the general population (GP), and 412 commercial sex workers (CSWs). High-risk sexual behaviors for HIV/AIDS were evident in both groups. Nevertheless, consistent condom use was reported by only 6% of the GP group, as compared to 67% of the CSWs. Failure to recognize high-risk routes for HIV infection was indicated in 69% of the GP women for anal sex, and by the majority of both groups for intercourse during menses (56% GP women and 54% CSWs). Multivariate analysis revealed that education level, actual age, and age of first sex experience were significant predictors of high-risk sexual practices. The necessity for educational programs regarding high-risk sexual practices and risk of HIV/ AIDS is evident for HIV/AIDS prevention.

Selenium and interleukins in persons infected with human immunodeficiency virus type 1.

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.

Zinc status in human immunodeficiency virus infection.

There is substantial evidence to support an important role for zinc in immune processes. Adequate zinc status is essential for T-cell division, maturation and differentiation; lymphocyte response to mitogens; programmed cell death of lymphoid and myeloid origins; gene transcription; and biomembrane function. Lymphocytes are one of the types of cells activated by zinc. Zinc is the structural component of a wide variety of proteins, neuropeptides, hormone receptors and polynucleotides. Among the best known zinc-dependent hormones/enzymes are Cu, Zn superoxide dismutase, an enzyme component of the antioxidant defense system, and thymulin, which is essential for the formation of T-lymphocytes. In animals and humans, zinc deficiency results in rapid and marked atrophy of the thymus, impaired cell-mediated cutaneous sensitivity and lymphopenia. Primary and secondary antibody responses are reduced in zinc deficiency, particularly for those antigens that require T-cell help, such as those in heterologous red blood cells. In addition, antibody response and the generation of splenic cytotoxic T cells after immunization are reduced. Zinc also inhibits the production of tumor necrosis factor, which is implicated in the pathophysiology of cachexia and wasting in acquired immune deficiency syndrome.

Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men.

OBJECTIVE: An examination of the relationship of plasma cobalamin (vitamin B(12)) level to overall psychological distress, specific mood states, and major depressive disorder was conducted in 159 bereaved men (90 HIV-1(+) and 69 HIV-1(-)). METHODS: The relationship of a continuous measure of cobalamin level to psychological distress was examined, while controlling for HIV-1 serostatus, life stressors, social support, and coping styles. RESULTS: Of this sample, 23.9% were either overtly or marginally cobalamin deficient; however, the deficiency rate was not significantly different by HIV-1 serostatus. Cobalamin level was inversely related to self-reported overall distress level and specifically to depression, anxiety, and confusion subscale scores, as well as to clinically rated depressed and anxious mood. Lower plasma cobalamin levels also were associated with the presence of symptoms consistent with major depressive disorder. CONCLUSION: These findings suggest that cobalamin level may be physiologically related to depressed and anxious mood level, as well as to syndromal depression.

When obesity is desirable: a longitudinal study of the Miami HIV-1-infected drug abusers (MIDAS) cohort.

Despite widespread nutrient deficiencies, a substantial proportion of the MIDAS cohort exhibits obesity, which has been linked to immune dysregulation in other clinical settings. Herein, the effects of obesity on immune function, disease progression, and mortality were evaluated longitudinally in 125 HIV-1-seropositive drug users, with comparison measures in 148 HIV-1-seronegative controls. Data were collected at a community clinic from 1992 to 1996, before administration of highly active antiretroviral therapy. Results indicated that overweight/obesity, defined as body mass index (BMI; kg/m2) > or =27, was evident in 18% of the HIV-1-seropositive patients and 29% of the seronegative patients. At baseline, no significant immunologic differences were observed among lean, nonobese, and obese groups. Over an 18-month period, 60.5% of the nonobese HIV-1-seropositive patients exhibited a 25% decline in CD4 cell count, compared with 18% of the obese patients (p<.004). During the follow-up period, 38% of the lean and 13% of the nonobese study subjects died of HIV-1-related causes. Measurements of BMI were inversely associated with progression to death, independent of CD4 count <200 cells/mm3 (p<.02). These data suggest that mild-to-moderate obesity in HIV-1-infected chronic drug users does not impair immune function and is associated with better HIV-1-related survival.

Diagnosis of human immunodeficiency virus infection using an immunoglobulin E-based assay.

Immunoglobulin assays that are sensitive and specific for detecting human immunodeficiency virus type 1 (HIV-1) infection are especially important in developing countries where PCR and viral culture may not be readily available. Immunoglobulin E (IgE), which is elevated in HIV-1 infection, is the only antibody that does not cross the placenta, making it potentially valuable for viral detection in both children and adults. This study developed an assay for detection of HIV specific IgE antibodies in adults. A total of 170 serum samples from 170 adults (116 HIV positive and 54 HIV negative) were analyzed. Serum or plasma samples were treated by using the protein G affinity method. The HIV status was determined by using two IgG enzyme-linked immunosorbent assays (ELISAs) and one Western blot evaluation. The IgE enzyme immunoassay test for HIV-1 correctly identified the HIV status in 98.8% of the samples (168 of 170). One false-positive and one false-negative test occurred with the IgE ELISA, as well as with the IgG ELISA test but were correctly identified by the IgE test. Analysis of the data demonstrated a high specificity (99%) and sensitivity (99%) of the IgE test, with 95% confidence intervals. The IgE assay appears to be sensitive and specific, suggesting that IgE-specific antibodies offer an effective method to detect HIV-1 infection in adults.