Lives saved by expanding HIV treatment availability in resource-limited settings: the example of Haiti.

BACKGROUND: Guidelines recommend antiretroviral therapy (ART) initiation at CD4 <350 cells per microliter for HIV-infected individuals in resource-limited settings. However, funding for treatment expansion remains uncertain. We forecast the mortality impact of ART expansion alternatives in Haiti. METHODS: We used data from Haiti to develop a country-specific model of HIV disease. The model projects the mortality, total number of HIV-infected individuals, and number and coverage (percentage of those eligible) on ART by simulating cohorts of HIV-infected individuals over 10 years. Five ART expansion scenarios, ranging from fully expanded ART (best case) to No New ART (worst case), were assessed. RESULTS: By 2010, the model predicts 103,500 individuals living with HIV in Haiti, of whom 27,300 were estimated to receive ART. Continuing ART initiation at current rates requires increasing the number on ART to 43,300 by 2020 (56% coverage), with 89,700 deaths estimated between 2010 and 2020. The number on ART could increase by 7400 (+17.1%, best case) or decrease by 25,600 (-59.1%, worst case), resulting in 19,500 deaths averted and 9900 fewer in care awaiting ART (best versus worst case). Results are sensitive to untreated disease progression and pre-ART loss from care. Increased HIV testing, linkage to care, and retention in care can avert additional deaths and achieve nearly 80% ART coverage with optimal policy improvements. CONCLUSIONS: In resource-limited settings, continued improvements in HIV treatment access will save lives. Efforts to efficiently expand ART access should remain a global priority.

Long-term antiretroviral treatment outcomes in seven countries in the Caribbean.

OBJECTIVES: To report long-term HIV treatment outcomes in 7 Caribbean countries. DESIGN: Observational cohort study. METHODS: We report outcomes for all antiretroviral therapy (ART) naive adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. RESULTS: A total of 8203 patients were on ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14-50 months). The overall mortality was 13%: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender [hazard ratio (HR), 1.58; 95% confidence interval (CI): 1.33 to 1.87], body weight (HR, 0.85 per 10 pounds; 95% CI: 0.82 to 0.89), hemoglobin (HR, 0.84 per g/dL; 95% CI: 0.80 to 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 to 0.93), concurrent tuberculosis (HR, 1.58; 95% CI: 1.25 to 2.01) and age (HR, 1.19 per 10 years; 95% CI: 1.11 to 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad, and Haiti was not significantly different. A total of 75% of patients remained alive and in care at the end of the study period. CONCLUSIONS: Long-term mortality rates vary widely across the Caribbean countries. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent tuberculosis. Earlier ART initiation will be critical to improve the outcomes.

Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti.

BACKGROUND: In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. METHODS AND FINDINGS: Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS). CONCLUSIONS: Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510.

Early versus standard antiretroviral therapy for HIV-infected adults in Haiti.

BACKGROUND: For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain. METHODS: We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support. RESULTS: Between 2005 and 2008, a total of 816 participants--408 per group--were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P=0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P=0.01). CONCLUSIONS: Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)

An enantioselective double Diels-Alder approach to the tetracyclic framework of colombiasin A.

The complex tetracyclic carbon skeleton of colombiasin A is conveniently accessed through an enantioselective intermolecular Diels-Alder-sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence.