Cost-effectiveness of Tenofovir / Emtricitabine / Efavirenz versus Zidovudine / Lamivudine / Efavirenz as fist-line regimens for the treatment of HIV-infected patients in low-income settings

The Highly Active Antiretroviral Therapy (HAART) is the combination of at least three antiretroviral compounds. The combination purpose is to reduce the likelihood of drug resistance. However in the long-term the resistance to the first-line combination occurs and leads to treatment failure. Thus, a second-line and even a third-line regimen are recommended in the long run. [...] [P. 5] The two treatment alternatives under comparison: Tenofovir (300 mg) CO-formulated with Emtricitabine (200 mg) and Efavirenz (600 mg) currently known under the brand name Atripla (R) was introduced in July 2006 in the United States market. The excellent safety profile and ease of use make this combination a perfect first-line regimen in low-income settings. Therefore, this treatment option was recommended in WHO 2006 reviewed guidelines. Unfortunately, Tenofovir and Emtricitabine compounds are still costly and not yet widely available. For a matter of simplification this regimen is referred in this report as "the recent" therapy. Initially, we had in mind to consider the most frequently used first-line regimen in low-income countries (Stavudine / Larnivudme / Nevirapine) as a comparator for this economic evaluation. Unfortunately, according to the literature review results (see Annex 3); there was no data available comparing head to head the effectiveness of this regimen with the recent one. Instead, we selected a less frequently but commonly used first-line regimen in low-income countries as a comparator: Zidovudine, Lamivudine, Efavirenz. This combination has extensive experience in durability, safety and toxicity and seems to be an optimal choice for a first-line regimen according to the clinical trial group 384 team. Furthermore, Zidovudine, one of the compounds of this combination is now recommended as one of the preferred NNRTI [Non Nucleoside Reverse Transcriptase Inhibitors] options to be considered by countries instead of Stavudine (the most used NNRTI in limited-income countries). As this combination has been included in the WHO guidelines as a first-line therapy since 2003 when WHO launched the "3 by 5" scaling-up initiative, this combination of drugs is referred in this report as the "old" therapy. Objectives: The primary objective of this economic evaluation is to compare the two first-line HAARTs introduced above, in a low-income setting context. Both of these combinations are recommended by the 2006 WHO guidelines as potential first-line regimens. The secondary objective is to provide a simplified and comprehensible cost-effectiveness modeling tool in order to help policy makers, in resource-limited settings, make decisions about which first-line HAART to fund using the scarce resources available. [P. 6-7]

Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Health system context and implementation of evidence-based practices-development and validation of the Context Assessment for Community Health (COACH) tool for low- and middle-income settings

Background: The gap between what is known and what is practiced results in health service users not benefitting from advances in healthcare, and in unnecessary costs. A supportive context is considered a key element for successful implementation of evidence-based practices (EBP). There were no tools available for the systematic mapping of aspects of organizational context influencing the implementation of EBPs in low- and middle-income countries (LMICs). Thus, this project aimed to develop and psychometrically validate a tool for this purpose. Methods: The development of the Context Assessment for Community Health (COACH) tool was premised on the context dimension in the Promoting Action on Research Implementation in Health Services framework, and is a derivative product of the Alberta Context Tool. Its development was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases: (1) defining dimensions and draft tool development, (2) content validity amongst in-country expert panels, (3) content validity amongst international experts, (4) response process validity, (5) translation and (6) evaluation of psychometric properties amongst 690 health workers in the five countries. Results: The tool was validated for use amongst physicians, nurse/midwives and community health workers. The six phases of development resulted in a good fit between the theoretical dimensions of the COACH tool and its psychometric properties. The tool has 49 items measuring eight aspects of context: Resources, Community engagement, Commitment to work, Informal payment, Leadership, Work culture, Monitoring services for action and Sources of knowledge. Conclusions: Aspects of organizational context that were identified as influencing the implementation of EBPs in high-income settings were also found to be relevant in LMICs. However, there were additional aspects of context of relevance in LMICs specifically Resources, Community engagement, Commitment to work and Informal payment. Use of the COACH tool will allow for systematic description of the local healthcare context prior implementing healthcare interventions to allow for tailoring implementation strategies or as part of the evaluation of implementing healthcare interventions and thus allow for deeper insights into the process of implementing EBPs in LMICs.

Common mental disorders during pregnancy: prevalence and associated factors among low-income women in Sao Paulo, Brazil

To estimate the prevalence of common mental disorders (CMD) and factors associated with these disorders among pregnant women of low socio-economic status (SES) in Sao Paulo. We performed a cross-sectional study with 831 women in their 20th to 30th weeks of pregnancy, who were attending antenatal clinics in primary care in Sao Paulo, Brazil. CMD were assessed with the Clinical Interview Schedule-Revised. Crude and adjusted prevalence ratios and 95% CI were calculated to examine the association between CMD and exposure variables. The prevalence of CMD was 20.2% (95% CI 17.5 to 23.0). Age at current pregnancy and at first delivery, current obstetric complications, not having friends in the community, living in a crowded household, lower occupational status and history of previous psychiatric treatment were all independently associated with increased prevalence of CMD. CMD is highly prevalent among pregnant women of low SES seen in primary care settings in Sao Paulo. A combination of distal and proximal psychosocial factors increase the risk for CMD. Primary health care professionals need to be aware of how common CMD in such settings and properly trained to deal with CMD during pregnancy.

Food on a Low Income: Four households tell their story

The aim of this research was to investigate the everyday experiences of food on a low income among people in four household types on the island of Ireland (IOI). This research will inform safefood and other stakeholders targeting vulnerable groups. It should influence both policy and practical programmes such as community food initiatives and awareness campaigns. Why do low-income groups suffer more from diet-related ill health than other groups? Is it because a healthy diet is too expensive? Or what other forces are there at work? safefood commissioned this qualitative research for four different low-income household types to gain a deeper understanding of the dynamics behind food poverty. The research involved a qualitative approach to enable an exploration of the ‘why’ behind the statistics of food poverty. In total, thirteen focus groups were conducted amongst four household types: two parent household with children, single males, single older people and lone parents with children, on IOI in both rural and urban settings.

Tuberculosis after initiation of antiretroviral therapy in low-income and high-income countries

We examined the incidence of and risk factors for tuberculosis during the first year of highly active antiretroviral therapy in low-income (4540 patients) and high-income (22,217 patients) countries. Although incidence was much higher in low-income countries, the reduction in the incidence of tuberculosis associated with highly active antiretroviral therapy was similar: the rate ratio for months 7-12 versus months 1-3 was 0.48 (95% confidence interval, 0.36-0.64) in low-income countries and 0.36 (95% confidence interval, 0.26-0.50) in high-income countries. A low CD4 cell count at the start of therapy was the most important risk factor in both settings.

Discordant responses to potent antiretroviral treatment in previously naive HIV-1-infected adults initiating treatment in resource-constrained countries: the antiretroviral therapy in low-income countries (ART-LINC) collaboration

OBJECTIVES: To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. METHODS: The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR(+)IR(+)), virologic only (VR(+)IR(-)), immunologic only (VR(-)IR(+)), and nonresponse (VR(-)IR(-)). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. RESULTS: Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR(+)IR(+), 364 (19.0%) were VR(+)IR(-), 283 (14.8%) were (VR(-)IR(+)), and 193 (10.1%) were VR(-)IR(-). OF THE 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VRIR, 364 (19.0%) were VRIR, 283 (14.8%) were (VRIR), and 193 (10.1%) were VRIR. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. CONCLUSIONS: The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

BACKGROUND: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. OBJECTIVES: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. RESULTS: Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. CONCLUSION: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries.

BACKGROUND Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART. DESIGN Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS. METHODS The generalized additive model for location, scale, and shape was used to construct normative percentile curves for weight gain at 6, 12, 18, and 24 months following ART initiation. Cox proportional models were used to assess the association between lower percentiles (< 50th) of weight gain distribution at the different time points and subsequent death, virological suppression, and virological failure. RESULTS Among 7173 children from five regions of the world, 45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12, 18, and 24 months of ART was associated with increased risk of death, independent of baseline characteristics. Poor weight gain was not associated with increased hazards of virological suppression or virological failure. CONCLUSION Monitoring weight gain on ART using age-specific and sex-specific normative curves specifically developed for HIV-infected children on ART is a simple, rapid, sustainable tool that can aid in the identification of children who are at increased risk of death in the first year of ART.

Effect of child care subsidies on price and quality of care for low -income families

This dissertation examines the effect of regulations, resource and referral agencies, and subsidies on price and quality of care in child care centers. This research is based on a carefully developed conceptual framework that incorporates the factors affecting the demand and supply of child care. The first step in developing this framework is sketching out the structural equations. The structural equations help us understand the underlying behavior of individuals and firms making a decision. The exogenous variables are vector of attributes relating to family characteristics, child characteristics, regulations, subsidy, community characteristics and prices of inputs. Based on the structural equations, reduced form equations are estimated to find the effect of each of the exogenous variables on each of the endogenous variables. Reduced form equations help us answer public policy questions. The sample for this study is from the 1990 Profile of Child Care Settings (PCCS) data in which 2,089 center based programs were interviewed.^ Child/Staff Ratio (Group Level). Results indicate that among subsidies, only the state subsidy per child in poverty has a significant effect on the child/staff ratio at the group level. Presence of resource and referral agencies also increase the child/staff ratio at the group level. Also when the maximum center group size regulation for 25-36 months becomes more stringent, the child/staff ratio at the group level decreases.^ Child/Staff Ratio (Center Level). When the regulations for the maximum child/staff ratio for age groups 13-24 months and 37-60 months become lax, the child/staff ratio for the center increases. As the regulation for maximum group size for infants becomes stringent, the child/staff ratio decreases. An interesting finding is that as the regulations for maximum group size for age groups 13-24 months and 25-36 months become stringent, the child/staff ratio for the center increases. Another significant finding is that when a center is located in a rural area the child/staff ratio is significantly lower.^ Center Weighted Average Hourly Fees. Maximum group size regulations for age groups 25-36 months and 37-60 months have a negative effect on center hourly fee. Maximum child staff regulations for age groups 13-24 months and 37-60 months have a negative effect on center hourly fee. Maximum child staff regulations for age groups 0-12 months and 25-36 months have a positive effect on center hourly fee. Findings also indicate that the center average hourly price is lower when there is a resource and referral agency present. Cost adjusted prekindergarten funds and JOBS child care subsidies have a negative effect on average hourly fee. Cost adjusted social services block grant and state subsidy per child in poverty have a positive effect on the average hourly price. A major finding of this dissertation is the interaction of subsidy and regulatory variables.^ Another major finding is that child/staff ratio at the group level is lower when there is an interaction between geographic location and nature of center sponsorship. ^

Effect of child care subsidies on price and quality of care for low -income families

This dissertation examines the effect of regulations, resource and referral agencies, and subsidies on price and quality of care in child care centers. This research is based on a carefully developed conceptual framework that incorporates the factors affecting the demand and supply of child care. The first step in developing this framework is sketching out the structural equations. The structural equations help us understand the underlying behavior of individuals and firms making a decision. The exogenous variables are vector of attributes relating to family characteristics, child characteristics, regulations, subsidy, community characteristics and prices of inputs. Based on the structural equations, reduced form equations are estimated to find the effect of each of the exogenous variables on each of the endogenous variables. Reduced form equations help us answer public policy questions. The sample for this study is from the 1990 Profile of Child Care Settings (PCCS) data in which 2,089 center based programs were interviewed. Child/Staff Ratio (Group Level): Results indicate that among subsidies, only the state subsidy per child in poverty has a significant effect on the child/staff ratio at the group level. Presence of resource and referral agencies also increase the child/staff ratio at the group level. Also when the maximum center group size regulation for 25-36 months becomes more stringent, the child/staff ratio at the group level decreases. Child/Staff Ratio (Center Level): When the regulations for the maximum child/staff ratio for age groups 13-24 months and 37-60 months become lax, the child/staff ratio for the center increases. As the regulation for maximum group size for infants becomes stringent, the child/staff ratio decreases. An interesting finding is that as the regulations for maximum group size for age groups 13-24 months and 25-36 months become stringent, the child/staff ratio for the center increases. Another significant finding is that when a center is located in a rural area the child/staff ratio is significantly lower. Center Weighted Average Hourly Fees: Maximum group size regulations for age groups 25-36 months and 37-60 months have a negative effect on center hourly fee. Maximum child staff regulations for age groups 13-24 months and 37-60 months have a negative effect on center hourly fee. Maximum child staff regulations for age groups 0-12 months and 25-36 months have a positive effect on center hourly fee. Findings also indicate that the center average hourly price is lower when there is a resource and referral agency present. Cost adjusted prekindergarten funds and JOBS child care subsidies have a negative effect on average hourly fee. Cost adjusted social services block grant and state subsidy per child in poverty have a positive effect on the average hourly price. A major finding of this dissertation is the interaction of subsidy and regulatory variables. Another major finding is that child/staff ratio at the group level is lower when there is an interaction between geographic location and nature of center sponsorship.

Assessing the validity of a food frequency questionnaire among low-income women in São Paulo, southeastern Brazil

This study describes the validity of a food frequency questionnaire (FFQ) in 93 low-income women (20-65 years), participating in a case-control study in São Paulo, Brazil. Two FFQ (FFQ1 and FFQ2, 12 months apart) and three 24-hour dietary recalls (24hR) were conducted between 2003 and 2004 to estimate dietary intake during the past year. The Pearson correlation coefficients (crude, energy-adjusted and de-attenuated) were used for comparisons between FFQ and 24hR. The agreement between the methods was further examined by the Bland-Altman analysis. For the assessment of long-term reliability, the energy-adjusted intra-class correlation coefficients were mostly around 0.40, but higher for vitamin A and folate (0.50-0.56). Energy-adjusted, attenuation-corrected Pearson validity correlations between FFQ and DR ranged from 0.30-0.54 for macronutrients to 0.20-0.48 for micronutrients, with higher value for calcium (0.75). There were small proportions of grossly misclassified nutrient intakes, while Bland-Altman plots indicated that the FFQ is accurate in assessing nutrient intake at a group level.

Nutritional status of pre-school children from low income families

Background: We evaluated growth and nutritional status of preschool children between 2 and 6 years old from low income families from 14 daycare centers. Methods: Cross-sectional study with 1544 children from daycare centers of Santo Andre, Brazil. Body weight (W), height (H) and body mass index (BMI) were classified according to the 2000 National Center for Health Statistics (CDC/NCHS). Cutoff points for nutritional disorders: -2 z scores and 2.5 and 10 percentiles for malnutrition risk, 85 to 95 percentile for overweight and above BMI 95 percentile for obesity. Stepwise Forward Regression method was used including age, gender, birth weight, breastfeeding duration, age of mother at birth and period of time they attended the daycare center. Results: Children presented mean z scores of H, W and BMI above the median of the CDC/NCHS reference. Girls were taller and heavier than boys, while we observed similar BMI between both genders. The z scores tended to rise with age. A Pearson Coefficient of Correlation of 0.89 for W, 0.93 for H and 0.95 for BMI was documented indicating positive association of age with weight, height and BMI. The frequency of children below -2 z scores was lower than expected: 1.5% for W, 1.75% for H and 0% for BMI, which suggests that there were no malnourished children. The other extremity of the distribution evidenced prevalence of overweight and obesity of 16.8% and 10.8%, respectively. Conclusion: Low income preschool children are in an advanced stage of nutritional transition with a high prevalence of overweight.

The prevalence of headache among elderly in a low-income area of Sao Paulo, Brazil

There are scarce data about headache prevalence and its characteristics among elderly people. The aim was to carry out a cross-sectional study to determine the 1-year prevalence of tension-type and migraine headaches in people > 65 years old in the city of Sao Paulo, Brazil. All 1615 people living in the study catchment area who agreed to participate in the study answered a questionnaire based in the International Headache Society criteria. Prevalence (mean and 95% confidence interval) of any type of headache in the last year was 45.6% (43.2, 48.0). Prevalence of tension-type headache in the last year was 33.1% (30.8, 35.4): 28.1% (24.6, 31.6) for men and 36.4% (33.4, 39.4) for women; for migraine headaches, prevalence in the last year was 10.6% (9.1, 12.1): 5.1% (3.4, 6.8) for men and 14.1% (11.9, 16.3) for women. One-year prevalence rates of headaches, and especially of migraine headaches, are very high among the elderly in Brazil.