Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries

The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

The Permanent Income Hypothesis: A Test on Czech Privatisation

Since the late eighties, economists have been regarding the transition from command to market economies in Central and Eastern Europe with intense interest. In addition to studying the transition per se, they have begun using the region as a testing ground on which to investigate the validity of certain classic economic propositions. In his research, comprising three articles written in English and totalling 40 pages, Mr. Hanousek uses the so-called "Czech national experiment" (voucher privatisation scheme) to test the permanent income hypothesis (PIH). He took as his inspiration Kreinin's recommendation: "Since data concerning the behaviour of windfall income recipients is relatively scanty, and since such data can constitute an important test of the permanent income hypothesis, it is of interest to bring to bear on the hypothesis whatever information is available". Mr. Hanousek argues that, since the transfer of property to Czech citizens from 1992 to 1994 through the voucher scheme was not anticipated, it can be regarded as windfall income. The average size of the windfall was more than three month's salary and over 60 percent of the Czech population received this unexpected income. Furthermore, there are other reasons for conducting such an analysis in the Czech Republic. Firstly, the privatisation process took place quickly. Secondly, both the economy and consumer behaviour have been very stable. Thirdly, out of a total population of 10 million Czech citizens, an astonishing 6 million, that is, virtually every household, participated in the scheme. Thus Czech voucher privatisation provides a sample for testing the PIH almost equivalent to a full population, thus avoiding problems with the distribution of windfalls. Compare this, for instance with the fact that only 4% of the Israeli urban population received personal restitution from Germany, while the number of veterans who received the National Service Life Insurance Dividends amounted to less than 9% of the US population and were concentrated in certain age groups. But to begin with, Mr. Hanousek considers the question of whether the public percieves the transfer from the state to individual as an increase in net wealth. It can be argued that the state is only divesting itself of assets that would otherwise provide a future source of transfers. According to this argument, assigning these assets to individuals creates an offsetting change in the present value of potential future transfers so that individuals are no better off after the transfer. Mr. Hanousek disagrees with this approach. He points out that a change in the ownership of inefficient state-owned enterprises should lead to higher efficiency, which alone increases the value of enterprises and creates a windfall increase in citizens' portfolios. More importantly, the state and individuals had very different preferences during the transition. Despite government propaganda, it is doubtful that citizens of former communist countries viewed government-owned enterprises as being operated in the citizens' best interest. Moreover, it is unlikely that the public fully comprehended the sophisticated links between the state budget, state-owned enterprises, and transfers to individuals. Finally, the transfers were not equal across the population. Mr. Hanousek conducted a survey on 1263 individuals, dividing them into four monthly earnings categories. After determining whether the respondent had participated in the voucher process, he asked those who had how much of what they received from voucher privatisation had been (a) spent on goods and services, (b) invested elsewhere, (c) transferred to newly emerging pension funds, (d) given to a family member, and (e) retained in their original form as an investment. Both the mean and the variance of the windfall rise with income. He obtained similar results with respect to education, where the mean (median) windfall for those with a basic school education was 13,600 Czech Crowns (CZK), a figure that increased to 15,000 CZK for those with a high school education without exams, 19,900 CZK for high school graduates with exams, and 24,600 CZK for university graduates. Mr. Hanousek concludes that it can be argued that higher income (and better educated) groups allocated their vouchers or timed the disposition of their shares better. He turns next to an analysis of how respondents reported using their windfalls. The key result is that only a relatively small number of individuals reported spending on goods. Overall, the results provide strong support for the permanent income hypothesis, the only apparent deviation being the fact that both men and women aged 26 to 35 apparently consume more than they should if the windfall were annuitised. This finding is still fully consistent with the PIH, however, if this group is at a stage in their life-cycle where, without the windfall, they would be borrowing to finance consumption associated with family formation etc. Indeed, the PIH predicts that individuals who would otherwise borrow to finance consumption would consume the windfall up to the level equal to the annuitised fraction of the increase in lifetime income plus the full amount of the previously planned borrowing for consumption. Greater consumption would then be financed, not from investing the windfall, but from avoidance of future repayment obligations for debts that would have been incurred without the windfall.

Poverty in Slovenia: A Conseqence of Economic Transition

Slovenia is considered to be one of the most successful Central and Eastern European countries undergoing the process of transition. It has a high GDP per capita (the highest in the Visegrad group) amounting to about 7200 US dollars (at the exchange rates pertaining during Ms. Stropnik's research). In 1994, a low rate of inflation, a low level of public debt and almost balanced public finances, were all positive elements. However, there is a darker side, for instance the dramatic increase in unemployment and (somewhat less dramatic) fall in production during the transition period. This analysis aimed to provide insights into what is actually happening at the household level, since households are the ultimate bearers of macroeconomic and social change. The final output totalled 166 pages in English and Slovenian, available also on disc. The income concept used by Ms. Stropnik is that of the disposable (monetary) household income, i.e. the cash income of all household members - including social security transfers and family benefits, and the net sum of taxes and social security contributions - plus the equivalent of domestic production, used in the household. Non-monetary income sources, such as household own production, benefits in kind, subsidies for goods and services, and fringe benefits, were not taken into account. The concept of relative and objective poverty was followed. Poverty means having less than others in society, it is a state of relative deprivation. Objective aspects of the situation, e.g. command over resources (i.e. the household income) and the relative position of the household in the income distribution, determine who is poor and who is not. Changes in household composition - an increase in the number of pensioners, unemployed and self-employed, concomitant with a large decrease in the number of employees - obviously played a part in the changing structure of household income sources during this period. The overall decrease in the share of wages and salaries from primary employment in 1993 is to be observed in all income deciles. On the other hand, the importance of salaries gained from secondary employment has increased in all deciles. The lower seven deciles experienced a sharp rise in the share of social benefits in the period 1988-1993, mostly because of the increase in the number of persons entitled to claim unemployment benefits. In Slovenia, income inequality has increased considerably during the 1988-1993 period. To make matters worse, the large increase in income inequality occurred in a period of falling real incomes. In 1983 the bottom decile disposed of 3.8 percent and the top decile disposed of 23.4 percent of total monetary income in Slovenia, whereas by 1993 the same statistics revealed 3.1 percent and 18.9 percent respectively. Unemployment greatly increases the risk of living in poverty. In 1993, 35 per cent of all unemployed persons in Slovenia were living in the lowest income quintile. Ms. Stropnik found certain features that were specific to Slovenia and not shared by most countries in transition. For example, the relative income position of pensioners has improved. Retirement did not increase the risk of poverty in 1993 as much as it did in 1983 and 1988. Also, it appears that children have not been particularly hard-hit by the transition upheavals. The incidence of poverty amongst children has not increased in the period 1983-1993. Children were also fairly evenly distributed across income quintiles. In 1983, 11.8 percent of households with children aged 18 or less were poor. In 1993, this figure was 8.4 per cent. On the other hand, poor households with children were, in comparison with other households of the same type, poorer in 1993 than in 1983. Ms. Stropnik also analysed the impact of social transfers. Her conclusion was that the level of social transfers prevented them from being successful in alleviating poverty. Family policy transfers (child allowances, child tax allowances, subsidised child care) did, however, contribute to the lowering of income inequality between families with and without children, and amongst families with different numbers of children. Ms. Stropnik is determined that the results of her research be used in the creation of social policy aimed at helping the poor. She quotes Piachaud approvingly: "If the term 'poverty' carries with it the implication and moral imperative that something should be done about it, then the study of poverty is only ultimately justifiable if it influences individual and social attitudes and actions."

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.

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.

Performance evaluation of VIP latrines in the Upper West Region of Ghana

The prevalence of Ventilated Improved Pit (VIP) latrines in Ghana suggests that the design must have a high user acceptance. The two key factors attributed to user acceptance of a VIP latrine over an alternative latrine design, such as the basic pit latrine, are its ability to remove foul odors and maintain low fly populations; both of which are a direct result of an adequate ventilation flow rate. Adequate ventilation for odorless conditions in a VIP latrine has been defined by the United Nations Development Program (UNDP) and the World Bank, as an air flow rate equivalent to 6 air changes per hour (6 ACH) of the superstructure’s air volume. Additionally, the UNDP determined that the three primary factors that affect ventilation are: 1) wind passing over the mouth of the vent pipe, 2) wind passing into the superstructure, and 3) solar radiation on to the vent pipe. Previous studies also indicate that vent pipes with larger diameters increase flow rates, and the application of carbonaceous materials to the pit sludge reduces odor and insect prevalence. Furthermore, proper design and construction is critical for the correct functioning of VIP latrines. Under-designing could cause problems with odor and insect control; over-designing would increase costs unnecessarily, thereby making it potentially unaffordable for benefactors to independently construct, repair or replace a VIP latrine. The present study evaluated the design of VIP latrines used by rural communities in the Upper West Region of Ghana with the focus of assessing adequate ventilation for odor removal and insect control. Thirty VIP latrines from six communities in the Upper West Region of Ghana were sampled. Each VIP latrine’s ventilation flow rate and micro-environment was measured using a hot-wire anemometer probe and portable weather station for a minimum of four hours. To capture any temporal or seasonal variations in ventilation, ten of the latrines were sampled monthly over the course of three months for a minimum of 12 hours. A latrine usage survey and a cost analysis were also conducted to further assess the VIP latrine as an appropriated technology for sustainable development in the Upper West Region. It was found that the average air flow rate over the entire sample set was 11.3 m3/hr. The minimum and maximum air flow rates were 0.0 m3/hr and 48.0 m3/hr respectively. Only 1 of the 30 VIP latrines (3%) was found to have an air flow rate greater than the UNDP-defined odorless condition of 6 ACH. Furthermore, 19 VIP latrines (63%) were found to have an average air flow rate of less than half the flow rate required to achieve 6 ACH. The dominant factors affecting ventilation flow rate were wind passing over the mouth of the vent pipe and air buoyancy forces, which were the effect of differences in temperature between the substructure and the ambient environment. Of 76 usable VIP latrines found in one community, 68.4% were in actual use. The cost of a VIP latrine was found to be equivalent to approximately 12% of the mean annual household income for Upper West Region inhabitants.

The impact of balsamo (Myroxylon balsamum L. Harms) on coffee yield and household income in El Balsamar, El Salvador

El Balsamar is a community that relies upon coffee trees intercropped with the balsamo tree (Myroxylon balsamum L. Harms) for a substantial portion of household income. The balsamo tree is valued for its resin which is used as medicine in the community and sold commercially. Farmers believe that the shade from the balsamo tree decreases coffee yield compared to the shade from non balsamo species. Thirty coffee farms were studied, each set up as a paired plot. When cover type was balsamo, coffee yield was more likely to decrease. Plots with higher basal area were more likely to be balsamo cover type. As basal area increased, coffee yield decreased. Although coffee yield is lower under balsamo cover type, farmers still continue to plant and manage coffee under this cover type. Farmers accept a lower coffee yield because balsamo resin provides an important income source. Farmers rely on the community cooperative to provide them work to support their households. The cooperative relies on the farmers to provide the labor needed to harvest coffee and extract balsamo resin.

Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries

OBJECTIVE: To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. METHODS: Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. FINDINGS: Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). CONCLUSION: Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.

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.

Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.