Early versus Standard Antiretroviral Therapy for HIV-Infected Adults in Haiti

Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, Port au Prince, Haiti.
New England Journal of Medicine (Impact Factor: 55.87). 07/2010; 363(3):257-65. DOI: 10.1056/NEJMoa0910370
Source: PubMed


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.
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.
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).
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. ( number, NCT00120510.)

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Available from: Catherine Godfrey, Dec 12, 2013
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    • "Our study had a similar design as the Haitian study by Severe et al [6], who started their study in 2005 and had AIDS as their clinical exclusion criterion. When our study started two years later, the CD4 criteria in Cameroon followed WHO and national guidelines, with ART-start when CD4 dropped below 200 cells/mm3. "
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    ABSTRACT: BackgroundOptimal starting point for antiretroviral treatment (ART) has been uncertain.MethodsParallel group, single blind, randomised controlled study of adult HIV positive patients consulting at the Protestant Hospital, Ngaoundere, Cameroon in 2007-8. Simple randomisation of patients in WHO clinical stage 1-2 to start of ART early or deferred, i.e. when CD4 counts dropped below 350 versus 250 cells/mm3, or when they reached clinical stage 3-4. Clinical follow-up every three months were offered for all patients. Main outcomes were clinical stage, CD4 differences and mortality. Of 424 consulting patients, most were excluded, mainly because they were already in WHO stage 3-4. Forty-four patients were randomised.ResultsIn the ‘early’ group two patients died and five were lost to follow-up. In the ‘deferred’ group, six patients died and nine were lost to follow-up (Hazard ratio for death by early compared to deferred treatment 0.26, 95% confidence interval 0.05-1.29). Of the patients lost to follow-up, three patients in the ‘early’ group and four patients in the ‘deferred’ group were known to be alive when the study ended. Fourteen patients in the early group and 11 in the deferred group started ART. Twenty-two patients were evaluated clinically six to seven months after the study period was terminated. Except for one patient with AIDS, these were all still in clinical stage 1-2.ConclusionsIn our small sample, relative risk for death did not differ significantly, but deferred treatment seemed to carry no increased survival or other clinical advantage. During the study period, other studies made WHO change its guidelines to conform to our early treatment. The tendency in our study lends support to this policy.Trial registrationISRCTN22114173Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2458-14-828) contains supplementary material, which is available to authorized users.
    Full-text · Article · Aug 2014 · BMC Public Health
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    • "Recent studies have documented that HIV-positive patients with tuberculosis (TB) who receive antiretroviral therapy (ART) within two weeks of beginning anti-tuberculosis treatment have lower mortality, particularly at low CD4 counts [1]–[4]. These findings prompted the World Health Organization (WHO) to revise its guidelines in 2012, urging initiation of ART “as a matter of emergency (within two weeks of starting anti tuberculosis treatment)” in patients with CD4 counts <50 cells/µl and “as early as possible” in others. "
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    ABSTRACT: Clinical trials have shown that early initiation of antiretroviral therapy in HIV-infected patients with tuberculosis saves lives, but models for implementation of this new strategy have been under-studied in real-world settings. To identify the barriers and possible solutions for implementing concurrent early treatment with antiretroviral and anti-tuberculosis therapy in a large East African referral hospital where the prevalence of both infections is high. In-depth interviews among hospital administrators, laboratory technicians, nurses, pharmacists, and physicians. Twenty-six hospital staff identified six key barriers and corresponding solutions to promote rapid initiation of antiretroviral therapy in HIV-infected inpatients with tuberculosis. These include revising systems of medication delivery, integrating care between inpatient and outpatient systems, training hospital nurses to counsel and initiate medications in inpatients, and cultivating a team approach to consistent guideline implementation. Most barriers identified by hospital staff were easily surmountable with reorganization, training, and policy changes at minimal cost. Efforts to reduce mortality for HIV and tuberculosis co-infected patients in accordance with new World Health Organization guidelines are currently hampered by implementation barriers in real-world settings. Our findings suggest that these can be overcome with strategic enactment of simple, realistic interventions to promote early dual treatment for HIV/tuberculosis co-infected patients.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "HCT alone reduces high-risk behaviors [5], and anti-retroviral therapy (ART) reduces transmission of HIV [16]. Starting ART before the CD4 count falls below 200 cells/µL results in nearly double the years of life gained from treatment than implementing ART at CD4 counts below 200 cells/µL [17], and starting ART before the CD4 count falls below 350 cells/µL results in further decreases in mortality and incident tuberculosis than starting at a threshold of 200 cells/µL [18]. However, advanced presentation at the time of diagnosis is common [19], obviating these benefits. "
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    ABSTRACT: The World Health Organization (WHO) recommends HIV Counseling and Testing (HCT) in a range of clinical settings. We describe the characteristics of patients diagnosed with HIV on the medical and surgical wards at a tertiary care hospital in Malawi. Under the universal opt-out HCT protocol we characterized the number of new HIV/AIDS infections and associated clinical features among hospitalized surgical and medical patients diagnosed during the course of admission. All 2985 and 3959 medical and surgical patients, respectively, admitted between April 2012 and January 2013 were screened for HCT. 62% and 89% of medical and surgical patients, respectively, had an unknown status on admission and qualified for testing. Of the patients with an unknown status, a new HIV diagnosis was made in 20% and 7% of medical and surgical patients, respectively. Of the newly diagnosed patients with a CD4 count recorded, 91% and 67% of medical and surgical patients, respectively, had a count less than 350, qualifying for ART by Malawi ART guidelines. Newly HIV-diagnosed medical and surgical patients had an inpatient mortality of 20% and 2%, respectively. While newly diagnosed HIV-positive medical patients had high inpatient mortality and higher rates of WHO stage 3 or 4 conditions, surgical patients presented with less advanced HIV, though still meeting ART initiation guidelines. The medical inpatient wards are an obvious choice for implementing voluntary counseling and testing (VCT), but surgical patients present with less advanced disease and starting treatment in this group could result in more years of life gained.
    Full-text · Article · Dec 2013 · Tropical Medicine and Health
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