Economic risk factors for HIV infection among women in rural Haiti: implications for HIV prevention policies and programs in resource-poor settings.

AIMS: The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population. METHODS: Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%. RESULTS: In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection. CONCLUSIONS: Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.

Northern Uganda and paradigms of HIV prevention: the need for social analysis.

In settings of armed conflict, traditional HIV prevention programmes that promote risk avoidance via abstinence and fidelity and risk reduction via condom use and needle exchange are not viable. In such contexts, HIV risk depends less on personal choice than on exposure to physical, emotional and structural violence. War in northern Uganda has created three realities (internally displaced people's camps, night commuters and child abductions) which increase vulnerability to HIV transmission. Based upon this analysis of northern Uganda, we offer a conceptual framework for HIV transmission in conflict settings that recognizes the importance of local and global context in creating vulnerability to HIV infection. This framework is then used to delineate strategies for HIV prevention in northern Uganda, namely the provision of a safe physical environment and access to education, medical and psychological support, and the promotion of conflict resolution strategies and human rights law.

Expanding global HIV treatment: case studies from the field.

In the last 25 years, human immunodeficiency virus (HIV) has become the leading infectious killer of adults globally, with an estimated 44 million people infected with the virus worldwide. Most of these individuals live in poor regions of the world, particularly sub-Saharan Africa. Although a great deal of work has been done in identifying and treating individuals with the disease, there has been little action to date to address the complex socioeconomic factors that lie at the heart of this global pandemic. Understanding and responding to such factors is of paramount importance if HIV infection is to be managed in a meaningful way. This article explores the social context of people living with HIV in three different geographic and epidemiologic settings and highlights the social factors that shape and define an individual's risk of acquiring HIV. It also discusses unique programs aimed at addressing the complex realities of the world in which HIV thrives. These programs can act as models of HIV prevention and treatment.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.

Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.

BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the toxicity of second-line medications. Little is known about whether adverse events impact treatment outcome. METHODS: We conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk between 10 September 2000 and 10 September 2002. Adverse reactions were determined by laboratory data and/or clinical criteria. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome. RESULTS: In this cohort, 76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were observed in 73.3% of patients, occurring in 74.8% of patients who were adherent (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals (P = 0.11). The impact of adverse events on outcome was modified by non-adherence; among adherent patients, the occurrence of any adverse reaction was associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval 1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence of adverse reactions among adherent patients was associated with treatment cure.

Community health workers as a cornerstone for integrating HIV and primary healthcare.

Haiti is the poorest and most heavily HIV-burdened country in the Western hemisphere, with even less health infrastructure than many countries of sub-Saharan Africa. Since the early 1980s the HIV epidemic has affected the poorest communities in Haiti, who lack access to even basic healthcare. Large-scale HIV treatment requires that basic healthcare services be built and scaled up simultaneously with HIV-prevention and -care programmes. Such improvement in access to general healthcare will require substantial investments in health infrastructure, service delivery and human development. This study describes the contribution of the non-governmental organization, Zanmi Lasante (ZL) to the HIV prevention and treatment scale-up and to the ongoing efforts to improve primary healthcare (PHC) services in the public health system in Haiti. The model depends on community health workers (CHWs) who supervise antiretroviral therapy (ART) and provide community outreach, including active case finding and outreach to marginalized populations. Zanmi Lasante has recruited, trained and financed a large cadre of CHWs to provide such linkages between communities and health centres in rural Haiti. The study analysed key components of their work--their self-perception, their role in enhancing community uptake of services and their role in targeting vulnerable groups. We found that most patients at risk were properly identified at a community level. The CHWs are facilitating the uptake of PHC services, including by the most vulnerable households. The general training of CHWs has created a positive self-definition in these cadres of their medical, patient support and health service roles; although with some variability across different groups. The results of this study will be used to emphasize, standardized and strengthen the biosocial training of CHWs.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising access to treatment in a resource poor setting.

OBJECTIVE: To develop a risk assessment algorithm that will increase the identification and treatment of women with cervical infection in rural Haiti. METHODS: Study participants were randomly selected from new patients who accessed services at a women's health clinic in rural Haiti between June 1999 and December 2002. This case-control study included women who tested positive for chlamydia and/or gonorrhoea based on the Gen-Probe PACE 2 laboratory test as cases. Controls were women who tested negative for both of these infections. RESULTS: Women from this area of rural Haiti had a limited level of education and lived in impoverished housing conditions. The sensitivity estimates of Haitian Ministry of Health and WHO algorithms for detecting chlamydia and/or gonorrhoea were generally low (ranging from 16.1% to 68.1%) in this population. Risk scores based on logistic regression models of local risk factors for chlamydia and gonorrhoea were developed and sensitivity estimates were higher for algorithms based on these risk scores (up to 98.8%); however, specificity was compromised. CONCLUSIONS: A risk assessment algorithm to identify women with chlamydia and/or gonorrhoea is more sensitive and less specific than the syndromic management approach advocated by WHO and adapted by the Haitian Ministry of Health. Using a risk assessment tool with high sensitivity based on local risk factors of cervical infection will maximise access to care, improve outcomes, and decrease morbidity in women who have cervical infection in rural Haiti.

Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB.

BACKGROUND: There is no gold standard on how national tuberculosis programs should design retreatment regimens. Often drug susceptibility testing (DST) is not available for all patients, and representative DST patterns in patient populations are used to guide therapy. OBJECTIVES: To examine DST patterns in different patient populations based on previous treatment and to estimate the number of effective anti-tuberculosis agents in several retreatment regimens. METHODS: We reviewed DST results from patients treated with individualized regimens in Peru between January 1998 and July 2004. We stratified patients into four groups based on previous treatment exposure from Group 1 who had failed only one regimen to Group 4 who had failed three regimens. We compared resistance frequencies across the four groups. In Groups 1 and 3, the number of likely effective agents under six possible retreatment regimen scenarios was estimated. RESULTS: Resistance to second-line drugs was significantly higher in groups with more previous courses of treatment. A few retreatment regimens could be identified that would allow at least 80% of patients to receive at least four likely effective drugs. CONCLUSION: Because it is associated with resistance frequencies, previous treatment exposure can serve to guide the design of non-individualized MDR-TB regimens.

Factors associated with forced sex among women accessing health services in rural Haiti: implications for the prevention of HIV infection and other sexually transmitted diseases.

The goals of the current study were to: (1) estimate the prevalence of forced sex among women accessing services at a women's health clinic in rural Haiti; and (2) examine factors associated with forced sex in this population. Based on data from a case-control study of risk factors for sexually transmitted diseases (STDs), a cross-sectional analysis to examine factors associated with forced sex was performed. A number of factors related to gender inequality/socioeconomic vulnerability placed women in rural Haiti at higher risk of forced sex. The strongest factors associated with forced sex in multivariate analyses were: age, length of time in a relationship, occupation of the woman's partner, STD-related symptoms, and factors demonstrating economic vulnerability. The findings suggest that prevention efforts must go beyond provision of information and education to the pursuit of broader initiatives at both local and national levels. At the community level, policy-makers should consider advancing economic opportunities for women who are vulnerable to forced sex. Improving access to community-based income-generating activities may begin to address this problem. However, the viability of these local projects depends largely upon Haiti's 'macro-economic' situation. In order to ensure the success of local initiatives, external humanitarian and development assistance to Haiti should be supported. By broadening the definition of "prevention" interventions, we may begin to address the systemic problems that contribute to the occurrence of forced sex and the increasing incidence of HIV infection throughout the world, such as gender inequality and economic vulnerability. Taking into account factors influencing risk at the local level as well as the macro-level will potentially improve our capacity to reduce the risk of forced sex and the spread of STDs, including HIV infection, for millions of women living in poverty worldwide.

From directly observed therapy to accompagnateurs: enhancing AIDS treatment outcomes in Haiti and in Boston.

Like tuberculosis, human immunodeficiency virus (HIV) disease is associated with poverty and social inequalities, conditions that hamper the delivery of care. Like tuberculosis, treatment of HIV infection requires multidrug regimens, and the causative agent acquires drug resistance, which can be transmitted to others. A pilot project in rural Haiti introduced DOT-HAART (directly observed therapy with highly active antiretroviral therapy) for the care of patients with advanced acquired immune deficiency syndrome. A similar DOT-HAART effort was launched in Boston for patients with drug-resistant HIV disease who had experienced failure of unsupervised therapy. In both settings, community health promoters or accompagnateurs provide more than DOT: they offer psychosocial support and link patients to clinical staff and available resources. DOT-HAART in these 2 settings presents both challenges and opportunities. These models of care can be applied to other poverty-stricken populations in resource-poor settings.

Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru.

SETTING: Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB. OBJECTIVE: To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs. RESULTS: Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy. CONCLUSIONS: Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection.

Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.

Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.