Tuberculosis Preventive Treatment Update - U.S. President's Emergency Plan for AIDS Relief, 36 Countries, 2016-2023.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.

Treatment success for patients with tuberculosis receiving care in areas severely affected by Hurricane Matthew - Haiti, 2016.

BACKGROUND: On October 4, 2016, Hurricane Matthew struck southwest Haiti as a category 4 storm. The goal of this study was to evaluate the impact of the hurricane on tuberculosis (TB) services and patient outcomes in the three severely affected departments-Sud, Grand'Anse, and Nippes-of southwest Haiti. METHODS: We developed a standard questionnaire to assess a convenience sample of health facilities in the affected areas, a patient tracking form, and a line list for tracking all patients with drug-susceptible TB registered in care six months before the hurricane. We analyzed data from the national TB electronic surveillance system to determine outcomes for all patients receiving anti-TB treatment in the affected areas. We used logistic regression analysis to determine factors associated with treatment success. RESULTS: Of the 66 health facilities in the three affected departments, we assessed 31, accounting for 536 (45.7%) of 1,174 TB patients registered in care when Hurricane Matthew made landfall in Haiti. Three (9.7%) health facilities sustained moderate to severe damage, whereas 18 (58.1%) were closed for <1 week, and five (16.1%) for ≥1 week. Four weeks after the hurricane, 398 (73.1%) of the 536 patients in the assessed facilities were located. Treatment success in the affected departments one year after the hurricane was 81.4%. Receiving care outside the municipality of residence (adjusted odds ratio [aOR]: 0.46, 95% confidence interval [CI]: 0.27-0.80) and HIV positivity (aOR: 0.31, 95% CI: 0.19-0.51) or unknown HIV status (aOR: 0.49, 95% CI: 0.33-0.74) were associated with significantly lower rates of treatment success. CONCLUSIONS: Despite major challenges, a high percentage of patients receiving anti-TB treatment before the hurricane were located and successfully treated in southwest Haiti. The lessons learned and results presented here may help inform policies and guidelines in similar settings for effective TB control after a natural disaster.

High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.

BACKGROUND: The main objective of this study was to determine the frequency and patterns of HIV drug resistance-associated mutations among children under 18 months of age born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission services in Haiti. METHODS: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots collected from children under 18 months of age for Early Infant Diagnosis at the National Public Health Laboratory were used for HIV-1 genotyping. HIV drug resistance mutations were analyzed using the Stanford Drug Resistance HIVdb program. RESULTS: Of the 3555 dried blood spots collected for Early Infant Diagnosis, 360 (10.1%) were HIV-positive and 355 were available for genotyping. Of these, 304 (85.6%) were successfully genotyped and 217 (71.4%) had ≥1 drug resistance mutation. Mutations conferring resistance to nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs were present in 40.5% (123) and 69.1% (210), respectively. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), G190A/S (15.1%), and Y181C/G/V (14.1%). Predicted drug resistance analysis revealed that 68.8% of the children had high-level resistance to non-NRTIs and 11.5% had intermediate to high-level resistance to abacavir. CONCLUSIONS: This study showed high rates of resistance to NRTIs and non-NRTIs among newly HIV-diagnosed children in Haiti, suggesting that in the era of "Option B+" (initiation of lifelong combination antiretroviral therapy to pregnant women with HIV), the majority of children who acquire HIV infection through mother-to-child transmission of HIV have resistant HIV. These results have led the National HIV Program to revise the pediatric guidelines to include protease inhibitors in first-line regimens for all HIV-positive newborns.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Virologic outcome among patients receiving antiretroviral therapy at five hospitals in Haiti.

INTRODUCTION: Viral load (VL) assessment is the preferred method for diagnosing and confirming virologic failure for patients on antiretroviral therapy (ART). We conducted a retrospective cross-sectional study to evaluate the virologic suppression rate among patients on ART for ≥6 months in five hospitals around Port-au-Prince, Haiti. METHODS: Plasma VL was measured and patients with VL <1,000 copies/mL were defined as virologically suppressed. A second VL test was performed within at least six months of the first test. Factors associated with virologic suppression were analyzed using logistic regression models accounting for site-level clustering using complex survey procedures. RESULTS: Data were analyzed for 2,313 patients on ART for six months or longer between July 2013 and February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the first VL test. A second VL test was performed within at least six months for 718 (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000 copies/mL who had a second VL performed, 394 (85.8%) maintained virologic suppression. Virologic suppression was negatively associated with male gender (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3 or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]). CONCLUSIONS: This study showed that over two-thirds of the patients in this evaluation achieved virologic suppression after ≥ six months on ART and the majority of them remained suppressed. These results reinforce the importance of expanding access to HIV-1 viral load testing in Haiti for monitoring ART outcomes.

Building and Rebuilding: The National Public Health Laboratory Systems and Services Before and After the Earthquake and Cholera Epidemic, Haiti, 2009-2015.

Before the 2010 devastating earthquake and cholera outbreak, Haiti's public health laboratory systems were weak and services were limited. There was no national laboratory strategic plan and only minimal coordination across the laboratory network. Laboratory capacity was further weakened by the destruction of over 25 laboratories and testing sites at the departmental and peripheral levels and the loss of life among the laboratory health-care workers. However, since 2010, tremendous progress has been made in building stronger laboratory infrastructure and training a qualified public health laboratory workforce across the country, allowing for decentralization of access to quality-assured services. Major achievements include development and implementation of a national laboratory strategic plan with a formalized and strengthened laboratory network; introduction of automation of testing to ensure better quality of results and diversify the menu of tests to effectively respond to outbreaks; expansion of molecular testing for tuberculosis, human immunodeficiency virus, malaria, diarrheal and respiratory diseases; establishment of laboratory-based surveillance of epidemic-prone diseases; and improvement of the overall quality of testing. Nonetheless, the progress and gains made remain fragile and require the full ownership and continuous investment from the Haitian government to sustain these successes and achievements.

Trends in Tuberculosis Case Notification and Treatment Success, Haiti, 2010-2015.

Since the 2010 earthquake, tuberculosis (TB) control has been a major priority for health sector response and recovery efforts in Haiti. The goal of this study was to analyze trends in TB case notification in Haiti from the aggregate data reported by the National TB Control Program to understand the effects of such efforts. A total of 95,745 TB patients were registered for treatment in Haiti between 2010 and 2015. Three regions, the West, Artibonite, and North departments accounted for 68% of the TB cases notified during the period. Patients in the 15-34 age groups represented 53% (50,560) of all cases. Case notification rates of all forms of TB increased from 142.7/100,000 in 2010 to 153.4 in 2015, peaking at 163.4 cases/100,000 in 2013. Case notification for smear-positive pulmonary TB increased from 85.5 cases/100,000 to 105.7 cases/100,000, whereas treatment success rates remained stable at 79-80% during the period. Active TB case finding efforts in high-risk communities and the introduction of new diagnostics have contributed to increasing TB case notification trends in Haiti from 2010 to 2015. Targeted interventions and novel strategies are being implemented to reach high-risk populations and underserved communities.

Transmission of Zika Virus - Haiti, October 12, 2015-September 10, 2016.

Zika virus disease is caused by infection with a flavivirus with broad geographic distribution and is most frequently transmitted by the bite of an infected mosquito. The disease was first identified in the World Health Organization's Region of the Americas in 2015 and was followed by a surge in reported cases of congenital microcephaly in Brazil; Zika virus disease rapidly spread to the rest of the region and the Caribbean (1), including Haiti. Infection with the virus is associated with adverse fetal outcomes (1) and rare neurologic complications in adults. The magnitude of public health issues associated with Zika virus led the World Health Organization to declare the Zika virus outbreak a Public Health Emergency of International Concern on February 1, 2016 (2). Because many persons with mild Zika virus disease are asymptomatic and might not seek care, it is difficult to estimate the actual incidence of Zika virus infection. During October 12, 2015-September 10, 2016, the Haitian Ministry of Public Health and Population (Ministère de la Santé Publique et de la Population [MSPP]) detected 3,036 suspected cases of Zika virus infection in the general population, 22 suspected cases of Zika virus disease among pregnant women, 13 suspected cases of Guillain-Barré syndrome (GBS), and 29 suspected cases of Zika-associated congenital microcephaly. Nineteen (0.6%) patients with suspected Zika virus disease, residing in Ouest (10 patients), Artibonite (six), and Centre (three) administrative departments,* have been confirmed by laboratory testing, including two among pregnant women and 17 in the general population. Ongoing laboratory-enhanced surveillance to monitor Zika virus disease in Haiti is important to understanding the outbreak and ensuring effective response activities.

Plasmodium falciparum K76T pfcrt Gene Mutations and Parasite Population Structure, Haiti, 2006-2009.

Hispaniola is the only Caribbean island to which Plasmodium falciparum malaria remains endemic. Resistance to the antimalarial drug chloroquine has rarely been reported in Haiti, which is located on Hispaniola, but the K76T pfcrt (P. falciparum chloroquine resistance transporter) gene mutation that confers chloroquine resistance has been detected intermittently. We analyzed 901 patient samples collected during 2006-2009 and found 2 samples showed possible mixed parasite infections of genetically chloroquine-resistant and -sensitive parasites. Direct sequencing of the pfcrt resistance locus and single-nucleotide polymorphism barcoding did not definitively identify a resistant population, suggesting that sustained propagation of chloroquine-resistant parasites was not occurring in Haiti during the study period. Comparison of parasites from Haiti with those from Colombia, Panama, and Venezuela reveals a geographically distinct population with highly related parasites. Our findings indicate low genetic diversity in the parasite population and low levels of chloroquine resistance in Haiti, raising the possibility that reported cases may be of exogenous origin.

Treatment outcomes for patients with multidrug-resistant tuberculosis in post-earthquake Port-au-Prince, Haiti.

We report outcomes and 12-month survival for the first cohort of patients to undergo multidrug-resistant tuberculosis (MDR-TB) treatment after the earthquake in Haiti. From March 3, 2010 to March 28, 2013, 110 patients initiated treatment of laboratory-confirmed MDR-TB at the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Center in Port-au-Prince, Haiti. Twenty-seven patients (25%) were human immunodeficiency virus (HIV)-positive. As of October 31, 2013, 95 (86%) patients were either cured or alive on treatment, 4 (4%) patients defaulted, and 11 (10%) patients died. Culture conversion occurred by 30 days in 14 (13%) patients, 60 days in 49 (45%) patients, and 90 days in 81 (74%) patients. The probabilities of survival to 12 months were 96% (95% confidence interval [95% CI] = 89-99) and 85% (95% CI = 64-94) for HIV-negative and -positive patients, respectively. Despite adverse conditions, outcomes for patients with MDR-TB are highly encouraging. Major efforts are underway to scale up community directly observed therapy and expand care to other regions of Haiti.

A multiplex PCR/LDR assay for simultaneous detection and identification of the NIAID category B bacterial food and water-borne pathogens.

Enteric pathogens that cause gastroenteritis remain a major global health concern. The goal of this study was to develop a multiplex PCR/ligation detection reaction (LDR) assay for the detection of all NIAID category B bacterial food and water-borne pathogens directly from stool specimens. To validate the PCR/LDR assay, clinical isolates of Campylobacter spp., Vibrio spp., Shigella spp., Salmonella spp., Listeria monocytogenes, Yersinia enterocolitica, and diarrheagenic Escherichia coli were tested. The sensitivity and specificity of the assay were assessed using a large number of seeded culture-negative stool specimens and a smaller set of clinical specimens from Haiti. The overall sensitivity ranged from 91% to 100% (median 100%) depending on the species. For the majority of organisms, the sensitivity was 100%. The overall specificity based on initial testing ranged from 98% to 100% depending on the species. After additional testing of discordant samples, the lowest specificity was 99.4%. PCR/LDR detected additional category B agents (particularly diarrheagenic E. coli) in 11/40 specimens from Haiti that were culture-positive for V. cholerae and in approximately 1% of routine culture-negative stool specimens from a hospital in New York. This study demonstrated the ability of the PCR/LDR assay to detect a large comprehensive panel of category B enteric bacterial pathogens as well as mixed infections. This type of assay has the potential to provide earlier warnings of possible public health threats and more accurate surveillance of food and water-borne pathogens.

Importance of cholera and other etiologies of acute diarrhea in post-earthquake Port-au-Prince, Haiti.

We estimated the proportion of diarrhea attributable to cholera and other pathogens during the rainy and dry seasons in patients seen in two urban health settings: a cholera treatment center (CTC) and oral rehydration points (ORPs). During April 1, 2011-November 30, 2012, stool samples were collected from 1,206 of 10,845 patients who came to the GHESKIO CTC or to the community ORPs with acute diarrhea, cultured for Vibrio cholerae, and tested by multiplex polymerase reaction. Vibrio cholerae was isolated from 409 (41.8%, 95% confidence interval [CI] = 38.7-44.9%) of the 979 specimens from the CTC and in 45 (19.8%, 95% CI = 14.8-25.6%) of the 227 specimens from the ORPs. Frequencies varied from 21.4% (95% CI = 16.6-26.7%) during the dry season to 46.8% (95% CI = 42.9-50.7%) in the rainy season. Shigella, enterotoxigenic Escherichia coli, rotavirus, and Cryptosporidium were frequent causes of diarrhea in children less than five years of age.

Predictors of disease severity in patients admitted to a cholera treatment center in urban Haiti.

Cholera, previously unrecognized in Haiti, spread through the country in the fall of 2010. An analysis was performed to understand the epidemiological characteristics, clinical management, and risk factors for disease severity in a population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A comprehensive review of the medical records of patients admitted during the period of October 28, 2010-July 10, 2011 was conducted. Disease severity on admission was directly correlated with older age, more prolonged length of stay, and presentation during the two epidemic waves seen in the observation period. Although there was a high seroprevalence of human immunodeficiency virus (HIV), severity of cholera was not greater with HIV infection. This study documents the correlation of cholera waves with rainfall and its reduction in settings with improved sanitary conditions and potable water when newly introduced cholera affects all ages equally so that interventions must be directed throughout the population.

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.

Virologic, clinical and immunologic responses following failure of first-line antiretroviral therapy in Haiti.

BACKGROUND: Since HIV-1 RNA (viral load) testing is not routinely available in Haiti, HIV-infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Data on survival and treatment outcomes for HIV-1 infected patients who meet criteria for ART failure are limited. We conducted a retrospective study to compare survival rates for patients who experienced failure on first-line ART by clinical and/or immunologic criteria and switched to second-line ART vs. those who failed but did not switch. METHODS: Patients receiving first-line ART at the GHESKIO Center in Port-au-Prince, Haiti, who met WHO clinical and immunologic criteria for failure were identified. Survival and treatment outcomes were compared in patients who switched their ART regimen and those who did not. Cox regression analysis was used to determine predictors of mortality after failure of first-line ART. RESULTS: Of 3126 patients who initiated ART at the GHESKIO Center between 1 March 2003 and 31 July 2008, 482 (15%) met WHO immunologic and/or clinical criteria for failure. Among those, 195 (41%) switched to second-line ART and 287 (59%) did not. According to Kaplan-Meier survival analysis, the probability of survival to 12 months after failure of first-line ART was 93% for patients who switched to second-line ART after failure and 88% for patients who did not switch. Predictors of mortality after failure of first-line ART were weight in the lowest quartile for sex, CD4 T cell count ≤ 100, adherence<90% at the time of failure and not switching to second-line ART. CONCLUSIONS: Patients who failed first-line ART based on clinical and/or immunologic criteria and did not switch to second-line therapy faced a higher mortality than those who switched after failure. To decrease mortality, interventions to identify patients in whom ART may be failing earlier are needed urgently. In addition, there is a major need to optimize second-line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients.

Clinical impact and cost of monitoring for asymptomatic laboratory abnormalities among patients receiving antiretroviral therapy in a resource-poor setting.

BACKGROUND: Laboratory monitoring for toxicity among patients receiving antiretroviral therapy (ART) in less-developed settings is technically challenging and consumes significant resources. METHODS: We conducted a cohort study of the 1800 adult patients who initiated ART at the Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) in Haiti from 2003 to 2006, using baseline data to establish the prevalence and using follow-up data to establish the incidence of hepatitis, renal insufficiency, hyperglycemia, anemia, neutropenia, and thrombocytopenia. We determined how frequently routine (not symptom-driven) testing detected significant laboratory abnormalities and calculated the cost per disability-adjusted life year (DALY) averted by detection of these events in the asymptomatic stage, compared with a strategy of symptom-prompted testing only. RESULTS: Forty-eight patients (3.5%) had severe anemia at baseline testing and consequently did not receive zidovudine. Fifty-three patients receiving zidovudine therapy developed severe anemia during follow-up (incidence, 2.5 cases/100 person-years). Monitoring for asymptomatic anemia with hematocrit testing was cost-saving at baseline and had a cost-effectiveness ratio of US$317/DALY averted during follow-up; with a complete blood count, costs increased to US$1182 and $10,781/DALY averted, respectively. With glucose monitoring, 11 patients were diagnosed with new-onset hyperglycemia during follow-up (incidence, 0.7 cases/100 person-years), resulting in a cost-effectiveness ratio of US$9845 per DALY averted. Monitoring for asymptomatic hepatitis and renal insufficiency was expensive and rarely affected care. CONCLUSIONS: Resource-poor countries should select which laboratory tests to perform on the basis of the cost-effectiveness of each test. This will depend on the national ART drug regimen and the prevalence of other comorbidities. Routine monitoring with multitest hematological and chemistry panels is unlikely to be cost-effective.

Survival, plasma HIV-1 RNA concentrations and drug resistance in HIV-1-infected Haitian adolescents and young adults on antiretrovirals.

OBJECTIVE: To assess outcomes after antiretroviral therapy (ART) in adolescents and youth in Haiti, a country with a generalized epidemic of infection with HIV-1. METHODS: An assessment was made of survival, plasma HIV-1 ribonucleic acid (RNA) concentrations and HIV-1 drug resistance patterns after 12 months of ART in patients aged 13-25 years who presented to a clinic in Port-au-Prince, Haiti, with AIDS between 1 March 2003 and 31 December 2005. Participants received ART in accordance with WHO guidelines. Kaplan-Meier analysis was used to estimate survival probabilities and their 95% confidence intervals (CI) for the period from ART initiation to death. FINDINGS: Of a total of 146 patients, 96 (66%) were female; the median CD4+ T-cell count at baseline was 129 cells/ml. By Kaplan-Meier analysis, 13% of the patients had died at 12 months, 17% at 24 months and 20% at 36 months. A plasma HIV-1 RNA concentration > or = 50 copies/ml was seen in 40 (51%) of 79 patients 12 months after treatment initiation and was associated with poor ART adherence. Among 29 patients with > 1000 copies/ml at 12 months, resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 23 cases (79%); to both NNRTIs and lamivudine in 21 (72%) cases; and to NNRTIs, lamivudine and other nucleoside reverse transcriptase inhibitors in 10 (35%) cases. One hundred and six participants (73%) reported sexual intercourse without condoms, and 35 of the 96 women (36%) were pregnant during follow-up. CONCLUSION: Adolescents and youth with AIDS receiving ART are at risk of virologic failure and disease progression and can therefore transmit HIV-1 to sexual partners and infants. Strategies to target the special needs of this age group are urgently needed.

Tuberculosis and HIV: Implications in the developing world.

Developing countries bear the brunt of the epidemics of AIDS and tuberculosis (TB), and the management of patients with both diseases poses a particular challenge in these settings. In this article, we review implications for the twin epidemics of HIV and TB for the developing world with respect to diagnosis, prevention, treatment and integration of national TB and HIV programs.

Antiretroviral therapy in a thousand patients with AIDS in Haiti.

BACKGROUND: The one-year survival rate of adults and children with the acquired immunodeficiency syndrome (AIDS), without antiretroviral therapy, has been about 30 percent in Haiti. Antiretroviral therapy has recently become available in Haiti and in other developing countries. Data on the efficacy of antiretroviral therapy in developing countries are limited. High rates of coinfection with tropical diseases and tuberculosis, along with malnutrition and limited laboratory monitoring of therapy, may decrease the efficacy of antiretroviral therapy in these countries. METHODS: We studied the efficacy of antiretroviral therapy in the first 1004 consecutive patients with AIDS and without previous antiretroviral therapy who were treated beginning in March 2003 in Port-au-Prince, Haiti. RESULTS: During a 14-month period, three-drug antiretroviral therapy was initiated in 1004 patients, including 94 children under 13 years of age. At enrollment, the median CD4 T-cell count in adults and adolescents was 131 per cubic millimeter (interquartile range, 55 to 211 per cubic millimeter); in children, a median of 13 percent of T cells were CD4-positive (interquartile range, 8 to 20 percent). According to a Kaplan-Meier survival analysis, 87 percent of adults and adolescents and 98 percent of children were alive one year after beginning treatment. In a subgroup of 100 adult and adolescent patients who were followed for 48 to 56 weeks, 76 patients had fewer than 400 copies of human immunodeficiency virus RNA per milliliter. In adults and adolescents, the median increase in the CD4 T-cell count from baseline to 12 months was 163 per cubic millimeter (interquartile range, 77 to 251 per cubic millimeter). In children, the median percentage of CD4 T cells rose from 13 percent at baseline to 26 percent (interquartile range, 22 to 36 percent) at 12 months. Treatment-limiting toxic effects occurred in 102 of the 910 adults and adolescents (11 percent) and 5 of the 94 children (5 percent). CONCLUSIONS: This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.