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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.

The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world. Copyright © 2006 World Health Organization [ABSTRACT FROM AUTHOR]

Background: Limited information exists on the impact of mobile health (mHealth) use by community health workers (CHWs) on improving the use of maternal health services in sub-Saharan Africa (SSA)., Objective: This systematic review addresses 2 objectives: evaluating the impact of mHealth use by CHWs on antenatal care (ANC) use, facility-based births, and postnatal care (PNC) use in SSA; and identifying facilitators and barriers to mHealth use by CHWs in programs designed to increase ANC use, facility-based births, and PNC use in SSA using a sociotechnical system approach., Methods: We searched for articles in 6 databases (MEDLINE, CINAHL, Web of Science, Embase, Scopus, and Africa Index Medicus) from inception up to September 2022, with additional articles identified from Google Scholar. After article selection, 2 independent reviewers performed title and abstract screening, full-text screening, and data extraction using Covidence software (Veritas Health Innovation Ltd). In addition, we manually screened the references lists of the included articles. Finally, we performed a narrative synthesis of the outcomes., Results: Among the 2594 records retrieved, 10 (0.39%) studies (n=22, 0.85% articles) met the inclusion criteria and underwent data extraction. The studies were published between 2012 and 2022 in 6 countries. Of the studies reporting on ANC outcomes, 43% (3/7) reported that mHealth use by CHWs increased ANC use. Similarly, of the studies reporting on facility-based births, 89% (8/9) demonstrated an increase due to mHealth use by CHWs. In addition, in the PNC studies, 75% (3/4) showed increased PNC use associated with mHealth use by CHWs. Many of the studies reported on the importance of addressing factors related to the social environment of mHealth-enabled CHWs, including the perception of CHWs by the community, trust, relationships, digital literacy, training, mentorship and supervision, skills, CHW program ownership, and the provision of incentives. Very few studies reported on how program goals and culture influenced mHealth use by CHWs. Providing free equipment, accessories, and internet connectivity while addressing ongoing challenges with connectivity, power, the ease of using mHealth software, and equipment maintenance support allowed mHealth-enabled CHW programs to thrive., Conclusions: mHealth use by CHWs was associated with an increase in ANC use, facility-based births, and PNC use in SSA. Identifying and addressing social and technical barriers to the use of mHealth is essential to ensure the success of mHealth programs., Trial Registration: PROSPERO CRD42022346364; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346364., (©Chiyembekezo Kachimanga, Haules Robbins Zaniku, Titus Henry Divala, Johannes C.F Ket, Joia S Mukherjee, Daniel Palazuelos, Alexandra V Kulinkina, Ibukun-Oluwa Omolade Abejirinde, Thomas van den Akker. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 24.09.2024.)

Objective: To retrospectively analyse routinely collected data on the drivers and barriers to retention in chronic care for patients with hypertension in the Kono District of Sierra Leone., Design: Convergent mixed-methods study., Setting: Koidu Government Hospital, a secondary-level hospital in Kono District., Participants: We conducted a descriptive analysis of key variables for 1628 patients with hypertension attending the non-communicable disease (NCD) clinic between February 2018 and August 2019 and qualitative interviews with 21 patients and 7 staff to assess factors shaping patients' retention in care at the clinic., Outcomes: Three mutually exclusive outcomes were defined for the study period: adherence to the treatment protocol (attending >80% of scheduled visits); loss-to-follow-up (LTFU) (consecutive 6 months of missed appointments) and engaged in (but not fully adherent) with treatment (<80% attendance)., Results: 57% of patients were adherent, 20% were engaged in treatment and 22% were LTFU. At enrolment, in the unadjusted variables, patients with higher systolic and diastolic blood pressures had better adherence than those with lower blood pressures (OR 1.005, 95% CI 1.002 to 1.009, p=0.004 and OR 1.008, 95% CI 1.004 to 1.012, p<0.001, respectively). After adjustment, there were 14% lower odds of adherence to appointments associated with a 1 month increase in duration in care (OR 0.862, 95% CI 0.801 to 0.927, p<0.001). Qualitative findings highlighted the following drivers for retention in care: high-quality education sessions, free medications and good interpersonal interactions. Challenges to seeking care included long wait times, transport costs and misunderstanding of the long-term requirement for hypertension care., Conclusion: Free medications, high-quality services and health education may be effective ways of helping NCD patients stay engaged in care. Facility and socioeconomic factors can pose challenges to retention in care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Lesotho is one of the 30 countries with the highest tuberculosis incidence rates in the world, estimated at 650 per 100,000 population. Tuberculosis case detection is extremely low, particularly with the rapid spread of COVID-19, dropping from an estimated 51% in 2020 to 33% in 2021. The aim of this study is to understand the barriers to tuberculosis diagnosis and treatment completion., Methods: We used a convergent mixed methods study design. We collected data on the number of clients reporting symptoms upon tuberculosis screening, their sputum test results, the number of clients diagnosed, and the number of clients who started treatment from one district hospital and one health center in Berea district, Lesotho. We conducted in-depth interviews and focus group discussions with 53 health workers and patients. We used a content analysis approach to analyze qualitative data and integrated quantitative and qualitative findings in a joint display., Findings: During March-August, 2019, 218 clients at the hospital and 292 clients at the health center reported tuberculosis symptoms. The full diagnostic testing process was completed for 66% of clients at the hospital and 68% at the health center. Among clients who initiated tuberculosis treatment, 68% (61/90) at the hospital and 74% (32/43) at the health center completed treatment. The main barriers to testing and treatment completion were challenges at sample collection, lack of decentralized diagnostic services, and socioeconomic factors such as food insecurity and high patient movement to search for jobs., Conclusions: Tuberculosis diagnosis could be improved through the effective decentralization of laboratory services at the health facility level, and treatment completion could be improved by providing food and other forms of social support to patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Andom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: As tuberculosis (TB) is an airborne disease requiring multi-month therapy, systems of TB detection and care were profoundly impacted by the COVID-19 pandemic. The worsening economic situation, including income, food, and housing insecurity, impacted the social conditions in which TB-already a leading killer in resource-limited settings-thrives. This study assesses the impact of COVID-19 on TB detection and treatment in Lesotho., Methods: We used routine program data from 78 health facilities in Lesotho. We created time series models from July 2018 to March 2021 to quantify COVID-19-related disruptions to TB program indicators: outpatient visits; presumptive, diagnosed, treated, and HIV co-infected cases; and treatment outcomes including successful (cured and completed) and unsuccessful (death and treatment outcome unknown)., Results: We observed a significant decline in cumulative outpatient visits (-37.4%, 95% prediction interval [PI]: -40.1%, -28.7%) and new TB cases diagnosed (-38.7%, 95%PI: -47.2%, -28.4%) during the pandemic, as well as TB-HIV co-infections (-67.0%, 95%PI: -72.6%, -60.0%). However, we observed no difference in treatment success (-2.1%, 95%PI: -17.0%, 15.8%)., Conclusions: TB case detection in Lesotho fell during the COVID-19 pandemic, likely related to the uptake of overall health services. However, treatment success rates did not change, indicating a strong health system and the success of local strategies to maintain treatment programs.

In 2014 the Kingdom of Lesotho, in conjunction with Partners In Health, launched a National Health Reform with three components: 1) improved supply-side inputs based on disease burden in the catchment area of each of 70 public primary care clinics, 2) decentralization of health managerial capacity to the district level, and 3) demand-side interventions including paid village health workers. We assessed changes in the quarterly average of quality metrics from pre-National Health Reform in 2013 to 2017, which included number of women attending their first antenatal care visit, number of post-natal care visits attended, number of children fully immunized at one year of age, number of HIV tests performed, number of HIV infection cases diagnosed, and the availability of essential health commodities. The number of health centers adequately equipped to provide a facility-based delivery increased from 3% to 95% with an associated increase in facility-based deliveries from 2% to 33%. The number of women attending their first antenatal and postnatal care visits rose from 1,877 to 2,729, and 1,908 to 2,241, respectively. The number of children fully immunized at one year of life increased from 191 to 294. The number of HIV tests performed increased from 5,163 to 12,210, with the proportion of patients living with HIV lost to follow-up falling from 27% to 22%. By the end of the observation period, the availability of essential health commodities increased to 90% or above. Four years after implementation of the National Health Reform, we observed increases in antenatal and post-natal care, and facility-based deliveries, as well as child immunization, and HIV testing and retention in care. Improved access to and utilization of primary care services are important steps toward improving health outcomes, but additional longitudinal follow-up of the reform districts will be needed., Competing Interests: The authors have nothing to declared no competing interests exist., (Copyright: © 2022 Ndayizigiye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lesotho has one of the highest tuberculosis (TB) incidence rates in the world, estimated at 654/100,000 population. However, TB detection remains low, with only 51% of people with TB being diagnosed and treated. The aim of this study was to evaluate implementation of TB screening and identify drivers of suboptimal TB screening in Lesotho. We used a convergent mixed methods study design. We collected data on the number of health facility visits and the number of clients screened for TB during March-August, 2019 from one district hospital and one health center. We conducted interviews and focus group discussions with patients and health workers to elucidate the mechanisms associated with suboptimal screening. Out of an estimated 70,393 visitors to the two health facilities, only 22% of hospital visitors and 48% of health center visitors were asked about TB symptoms. Only 2% of those screened at each facility said that they had TB symptoms, comprising a total of 510 people. Lack of training on tuberculosis screening, overall staff shortages, barriers faced by patients in accessing care, and health care worker mistrust of tuberculosis screening procedures were identified as drivers of suboptimal TB screening. TB screening could be improved by ensuring the availability of well-trained, incentivized, and dedicated screeners at health facilities, and by providing TB screening services in community settings., Competing Interests: The authors declare no competing interests., (Copyright: © 2022 Andom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on emergency and critical care (ECC) capacity in low-income countries (LICs) are needed to improve outcomes and make progress towards realizing the goal of Universal Health Coverage., Methods: We developed a novel research instrument to assess public sector ECC capacity and service readiness in LICs. From January 20th to February 18th, 2020 we administered the instrument at all four central hospitals and a simple random sample of nine of 24 district hospitals in Malawi, a landlocked and predominantly rural LIC of 19·1 million people in Southern Africa. The instrument contained questions on the availability of key resources across three domains and was administered to hospital administrators and clinicians from outpatient departments, emergency departments, and inpatient units. Results were used to generate an ECC Readiness Score, with a possible range of 0 to 1, for each facility., Findings: A total of 114 staff members across 13 hospitals completed interviews for this study. Three (33%) district hospitals and all four central hospitals had ECC Readiness Scores above 0·5 ( p -value 0·070). Absent equipment was identified as the most common barrier to ECC Readiness. Central hospitals had higher median ECC Readiness Scores with less variability 0·82 (interquartile range: 0·80-0·89) than district hospitals (0·33, 0·23 to 0·50, p -value 0·021)., Interpretation: This is the first study to employ a systematic approach to assessing ECC capacity and service readiness at both district and central hospitals in Malawi and provides a framework for measuring ECC capacity in other LICs. Prior ECC assessments potentially overestimated equipment availability and our methodology may provide a more accurate approach. There is an urgent need for investments in ECC services, particularly at district hospitals which are more accessible to Malawi's predominantly rural population. These findings highlight the need for long-term investments in health systems strengthening and underscore the importance of understanding capacity in LIC settings to inform these efforts., Funding: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Department of Emergency Medicine, Brigham and Women's Hospital., Competing Interests: PDS received support for this study from Brigham and Women's Hospital, Division of Pulmonary and Critical Care Medicine in the form of a faculty research fund and has received consulting fees from the University of California-San Francisco/Sustaining Technical and Analytic Resources as lead technical advisor for ventilator technical assistance in Haiti. SAR received support for this study in the form of a seed grant from Brigham and Women's Hospital Department of Emergency Medicine. JSM is the Chief Medical Officer at Partners In Health and sits on the boards of Village Health Works (Burundi/Muso and Mali), The Institute for Justice and Democracy in Haiti, and Free Speech for People., (© 2022 The Authors.)

Background: In Liberia, an estimated 32% of children under 5 are stunted. Malnutrition and hunger worsened during the country's civil war and were further exacerbated by the 2014-2016 outbreak of Ebola virus disease. Studies examining adherence to recommended infant and young child feeding practices frequently do so with an emphasis on the knowledge, attitudes and beliefs of mothers and caregivers. Often overlooked are the structural factors that enable or constrain their agency to practise evidence-based recommendations., Methods: Between July and December 2017, we surveyed 100 Liberian mothers to assess the sociodemographic factors associated with the risk of severe acute malnutrition in children in Maryland County, Liberia. We also conducted 50 in-depth interviews at two government health facilities to qualitatively explore mothers' experiences, as well as health workers' understandings of the determinants of malnutrition in the region. We applied logistic regression to analyse quantitative data and inductive content analysis to thematically interpret qualitative data., Results: Mothers were less likely to have a child with severe acute malnutrition if they had an income greater than US$50 per month (adjusted OR (aOR)=0.14, p<0.001), were literate (aOR=0.21, p=0.009) or exclusively breast fed during the first 6 months of life (aOR=0.18, p=0.049); they were more likely to have a child with severe acute malnutrition if they were married or in domestic partnerships (aOR=8.41, p<0.001). In-depth interviews elucidated several social, economic and programmatic factors that shaped suboptimal feeding practices, as well as decisions for and against seeking formal care for malnutrition., Discussion: The lived experiences of Liberian mothers and health workers illustrate that child malnutrition is a direct consequence of abject poverty, food insecurity, illiteracy, the precarious nature of formal and informal work, and the lack of robust social protection. Behaviour change and health education interventions that do not seek to alleviate structural barriers to compliance are unlikely to be effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen., Objectives: This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort., Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death., Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93)., Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Background: Although it is now widely recognized that reductions in maternal mortality and improvements in women's health cannot be achieved through simple, vertical strategies, few programs have provided successful models for how to integrate services into a comprehensive program for maternal health. We report our experience in rural Lesotho, where Partners In Health (PIH) in partnership with the Ministry of Health and Social Welfare implemented a program that provides comprehensive care of pregnant women from the community to the clinic level., Methods: Between May and July 2009, PIH trained 100 women, many of whom were former traditional birth attendants, to serve as clinic-affiliated maternal health workers. They received performance-based incentives for accompanying pregnant women during antenatal care (ANC) visits and facility-based delivery. A nurse-midwife provided ANC and delivery care and supervised the maternal health workers. To overcome geographic barriers to delivering at the clinic, women who lived far from the clinic stayed at a maternal lying-in house prior to their expected delivery dates. We analyzed data routinely collected from delivery and ANC registers to compare service utilization before and after implementation of the program., Results: After the establishment of the program, the average number first ANC visits increased from 20 to 31 per month. The clinic recorded 178 deliveries in the first year of the program and 216 in the second year, compared to 46 in the year preceding the program. During the first two years of the program, 49 women with complications were successfully transported to the district hospital, and no maternal deaths occurred among the women served by the program., Conclusions: Our results demonstrate that it is possible to achieve dramatic improvements in the utilization of maternal health services and facility-based delivery by strengthening human resource capacity, implementing active follow-up in the community, and de-incentivizing home births.

Background: Few studies have examined outcomes for children treated for multidrug-resistant tuberculosis (MDR-TB), including those receiving concomitant treatment for MDR-TB and HIV co-infection. In Lesotho, where the adult HIV seroprevalence is estimated to be 24%, we sought to measure outcomes and adverse events in a cohort of children treated for MDR-TB using a community-based treatment delivery model., Methods: We reviewed retrospectively the clinical charts of children ≤15 years of age treated for culture-confirmed or suspected MDR-TB between July 2007 and January 2011., Results: Nineteen children, ages two to 15, received treatment. At baseline, 74% of patients were co-infected with HIV, 63% were malnourished, 84% had severe radiographic findings, and 21% had extrapulmonary disease. Five (26%) children had culture-confirmed MDR-TB, ten (53%) did not have culture results available, and four (21%) subsequently had results indicating drug-susceptible TB. All children with HIV co-infection who were not already on antiretroviral therapy (ART) were initiated on ART a median of two weeks after the start of the MDR-TB regimen. Among the 17 patients with final outcomes, 15 (88%) patients were cured or completed treatment, two (12%) patients died, and none defaulted or were lost to follow-up. The majority of patients (95%) experienced adverse events; only two required permanent discontinuation of the offending agent, and only one required suspension of MDR-TB treatment for more than one week., Conclusions: Pediatric MDR-TB and MDR-TB/HIV co-infection can be successfully treated using a combination of social support, close monitoring by community health workers and clinicians, and inpatient care when needed. In this cohort, adverse events were well tolerated and treatment outcomes were comparable to those reported in children with drug-susceptible TB and no HIV infection.

Objectives: South-south collaborations in building human resource capacity have been inadequately emphasized globally despite the growing experience among resource-poor countries in scaling up HIV care and the funding to implement programmes. This paper aims to describe one such successful collaboration, in which a model of HIV care was developed in Haiti, adapted and expanded to Lesotho, and allowed the effective scale-up of HIV and other treatment services in a rural African setting., Methods: Institutional experiences and lessons learned over a 10-year period in Haiti and a 3-year period in Lesotho are discussed., Results: The Haiti-Lesotho collaborative model shows that human resource capacity can be built using creative partnerships and exchanges between developing countries, particularly with financial support from the north. The collaboration allows for the sharing of experiences and solutions through perspectives and experiences that are unique to developing countries. Healthcare workers in Haiti and Lesotho have established meaningful and fruitful cross-country working relationships, job satisfaction and retention has been improved and a sense of solidarity developed. The model of care developed in Haiti was successfully adapted, replicated and implemented in Lesotho., Conclusion: South-south collaborations are an important way for countries with established experience managing HIV in resource-poor settings to share their skills in a collaborative fashion with other nations facing similar disease problems and infrastructural challenges. This model for scaling up effective practice should be encouraged and supported by programme funders.

Background: Previous studies of Haitian immigrant and refugee youth have emphasized "externalizing" behaviors, such as substance use, high risk sexual behavior, and delinquency, with very little information available on "internalizing" symptoms, such as depression and anxiety. Analyzing stressors and "internalizing" symptoms offers a more balanced picture of the type of social and mental health services that may be needed for this population. The present study aims to: 1) estimate the prevalence of depression and post-traumatic stress disorder (PTSD) among Haitian immigrant students; and 2) examine factors associated with depression and PTSD to identify potential areas of intervention that may enhance psychosocial health outcomes among immigrant youth from Haiti in the U.S., Methods: A stratified random sample of Haitian immigrant students enrolled in Boston public high schools was selected for participation; 84% agreed to be interviewed with a standardized questionnaire. Diagnosis of depression and PTSD was ascertained using the best estimate diagnosis method., Results: The prevalence estimates of depression and PTSD were 14.0% and 11.6%; 7.9% suffered from comorbid PTSD and depression. Multivariate logistic regression demonstrated factors most strongly associated with depression (history of father's death, self-report of schoolwork not going well, not spending time with friends) and PTSD (concern for physical safety, having many arguments with parents, history of physical abuse, and lack of safety of neighborhood)., Conclusions: A significant level of depression and PTSD was observed. Stressors subsequent to immigration, such as living in an unsafe neighborhood and concern for physical safety, were associated with an increased risk of PTSD and should be considered when developing programs to assist this population. Reducing exposure to these stressors and enhancing access to social support and appropriate school-based and mental health services may improve educational attainment and psychosocial health outcomes among Haitian immigrant youth.

As HIV treatment is scaled-up in resource-poor settings, the timely identification of persons with HIV infection remains an important challenge. Most people with HIV are unaware of their status, and those who are often present late in the course of their illness. Free-standing voluntary counseling and testing sites often have poor uptake of testing. We aimed to evaluate a 'provider-initiated' HIV testing strategy in a primary care clinic in rural resource-poor Haiti by reviewing the number of visits made to clinic before an HIV test was performed in those who were ultimately found to have HIV infection. In collaboration with the Haitian Ministry of Health, a non-governmental organization (Partners In Health) scaled up HIV care in central Haiti by reinforcing primary care clinics, instituting provider-initiated HIV testing and by providing HIV treatment in the context of primary medical care, free of charge to patients. Among a cohort of people with HIV infection, we assessed retrospectively for delays in or 'missed opportunities' for diagnosis of HIV by the providers in one clinic. Of the first 117 patients diagnosed with HIV in one clinic, 100 (85%) were diagnosed at the first medical encounter. Median delay in diagnosis for the remaining 17 was only 62 days (IQR 19 - 122; range 1 - 272). There was no statistical difference in CD4 cell count between those with and without a delay. 3787 HIV tests were performed in the period reviewed. Provider-initiated testing was associated with high volume uptake of HIV testing and minimal delay between first medical encounter and diagnosis of HIV infection. In scale up of HIV care, provider-initiated HIV testing at primary care clinics can be a successful strategy to identify patients with HIV infection.

In northern Uganda, physical and structural violence (political repression, economic inequality, and gender-based discrimination) increase vulnerability to HIV infection. In settings of war, traditional HIV prevention that solely promotes risk avoidance and risk reduction and assumes the existence of personal choice inadequately addresses the realities of HIV transmission. The design of HIV prevention strategies in northern Uganda must recognize how HIV transmission occurs and the factors that put people at risk for infection. A human rights approach provides a viable model for achieving this aim.

Since 2002, the HIV Equity Initiative of the nongovernmental organization Partners in Health has been expanded in conjunction with the Haitian MOH to cover 7 public clinics. More than 8000 HIV-positive persons, 2300 of whom are on antiretroviral therapy (ART) are now followed. This article describes the interventions to promote access to care and adherence to ART developed in reference to the specific context of poverty in rural Haiti. User fees for clinic attendance have been waived for all patients with HIV and tuberculosis and for women presenting for prenatal services. Additionally, HIV testing has been integrated into the provision of primary care services to increase HIV case finding among those presenting to clinic because of illness, rather than solely focusing on those who present for voluntary counseling and testing (VCT). Once a patient is diagnosed with HIV, medications and monitoring tests are provided free of charge and transportation costs for follow-up appointments are covered to defray patients' out-of-pocket expenses. Patients are given home-based adherence support from a network of health workers who provide psychosocial support and directly observed therapy. In addition, the neediest patients receive nutritional support. Following the description of the program is an approximation of the costs of these interventions and a discussion of their impact.

Evidence of successful management of multidrug-resistant tuberculosis (MDRTB) is mainly generated from referral hospitals in high-income countries. We evaluate the management of MDRTB in 5 resource-limited countries: Estonia, Latvia, Peru, the Philippines, and the Russian Federation. All projects were approved by the Green Light Committee for access to quality-assured second-line drugs provided at reduced price for MDRTB management. Of 1047 MDRTB patients evaluated, 119 (11%) were new, and 928 (89%) had received treatment previously. More than 50% of previously treated patients had received both first- and second-line drugs, and 65% of all patients had infections that were resistant to both first- and second-line drugs. Treatment was successful in 70% of all patients, but success rate was higher among new (77%) than among previously treated patients (69%). In resource-limited settings, treatment of MDRTB provided through, or in collaboration with, national TB programs can yield results similar to those from wealthier settings.

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.

Lactic acidosis is a rare but potentially life-threatening complication of antiretroviral therapy (ART) and is commonly considered in the differential diagnosis of patients on ART. In the developing world, definitive diagnosis by laboratory measurement of lactate may be impossible. Point-of-care devices are available that provide simple, accurate measurements of lactic acid levels at relatively low cost. Their use in an HIV treatment programme in rural Haiti has greatly assisted clinical decision-making in patients with symptoms suggestive of lactic acidosis.

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.

Three decades ago, the world's ministries of health declared primary health care--the delivery of basic preventive and curative services--a top priority. Since then, however, the world's poorest countries have not met most primary health care goals. Twenty-six years after the Declaration of Alma Ata, we are said to be living in a time of "limited resources," a phrase that construes various health interventions as competing priorities. As HIV has become the leading infectious cause of adult death in much of the world, it is difficult to argue that AIDS prevention and care are not ranking priorities for primary health care, yet precisely such arguments have held sway among international health policy makers. We present new information emerging from the scale-up of an established and integrated AIDS prevention-and-care program, based initially in a squatter settlement in central Haiti, to a second site in rural Haiti. The program includes robust prevention efforts as well as community-based therapy for advanced AIDS; three related components--women's health and active case finding and therapy for tuberculosis and sexually transmitted infections--were central to this effort. We tracked changes in key indices over the 14 months following the introduction of these services to a public clinic in central Haiti. We found that integrated AIDS prevention and care, including the use of antiretroviral agents, to be feasible in resource-poor settings and that such efforts may have favorable and readily measured impact on a number of primary health care goals, including vaccination, family planning, tuberculosis case finding and cure, and health promotion. Other collateral benefits, though less readily measured, include improved staff morale and enhanced confidence in public health and medicine. We conclude that improving AIDS prevention and treatment can help to reinvigorate flagging efforts to promote universal primary health care.

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.