Timing of antiretroviral therapy in Cambodian hospital after diagnosis of tuberculosis: impact of revised WHO guidelines.

OBJECTIVE To determine if implementation of 2010 World Health Organization (WHO) guidelines on antiretroviral therapy (ART) initiation reduced delay from tuberculosis diagnosis to initiation of ART in a Cambodian urban hospital. METHODS A retrospective cohort study was conducted in a nongovernmental hospital in Phnom Penh that followed new WHO guidelines in patients with human immunodeficiency virus (HIV) and tuberculosis. All ART-naïve, HIV-positive patients initiated on antituberculosis treatment over the 18 months before and after guideline implementation were included. A competing risk regression model was used. FINDINGS After implementation of the 2010 WHO guidelines, 190 HIV-positive patients with tuberculosis were identified: 53% males; median age, 38 years; median baseline CD4+ T-lymphocyte (CD4+ cell) count, 43 cells/µL. Before implementation, 262 patients were identified; 56% males; median age, 36 years; median baseline CD4+ cell count, 59 cells/µL. With baseline CD4+ cell counts ≤ 50 cells/µL, median delay to ART declined from 5.8 weeks (interquartile range, IQR: 3.7-9.0) before to 3.0 weeks (IQR: 2.1-4.4) after implementation (P < 0.001); with baseline CD4+ cell counts > 50 cells/µL, delay dropped from 7.0 (IQR: 5.3-11.3) to 3.6 (IQR: 2.9-5.3) weeks (P < 0.001). The probability of ART initiation within 4 and 8 weeks after tuberculosis diagnosis rose from 23% and 65%, respectively, before implementation, to 62% and 90% after implementation. A non-significant increase in 6-month retention and antiretroviral substitution was seen after implementation. CONCLUSION Implementation of 2010 WHO recommendations in a routine clinical setting shortens delay to ART. Larger studies with longer follow-up are needed to assess impact on patient outcomes.

[1]  D. Havlir,et al.  Reducing deaths from tuberculosis in antiretroviral treatment programmes in sub-Saharan Africa , 2012, AIDS.

[2]  N. Ford,et al.  Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review , 2012, AIDS.

[3]  A. Boulle,et al.  The Effect of Complete Integration of HIV and TB Services on Time to Initiation of Antiretroviral Therapy: A Before-After Study , 2012, PloS one.

[4]  M. L. van der Walt,et al.  Missed opportunities for accessing HIV care among Tshwane tuberculosis patients under different models of care. , 2012, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[5]  W. Manosuthi,et al.  Time to Initiate Antiretroviral Therapy Between 4 Weeks and 12 Weeks of Tuberculosis Treatment in HIV-Infected Patients: Results From the TIME Study , 2012, Journal of acquired immune deficiency syndromes.

[6]  L. Smeaton,et al.  Operationalizing early antiretroviral therapy in HIV-infected in-patients with opportunistic infections including tuberculosis. , 2012, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[7]  R. Wilkinson,et al.  Assessment at Antiretroviral Clinics during TB Treatment Reduces Loss to Follow-Up among HIV-Infected Patients , 2012, PloS one.

[8]  B. Castelnuovo,et al.  Integration of HIV and TB Services Results in Improved TB Treatment Outcomes and Earlier Prioritized ART Initiation in a Large Urban HIV Clinic in Uganda , 2012, Journal of acquired immune deficiency syndromes.

[9]  D. Havlir,et al.  HIV and tuberculosis – science and implementation to turn the tide and reduce deaths , 2012, Journal of the International AIDS Society.

[10]  L. Lynen,et al.  Incidence of Treatment-Limiting Toxicity with Stavudine-Based Antiretroviral Therapy in Cambodia: A Retrospective Cohort Study , 2012, PloS one.

[11]  F. van Leth,et al.  Comment on: predictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia. , 2011, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[12]  James Macinko,et al.  Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: a systematic review. , 2011, The Lancet. Infectious diseases.

[13]  D. Gareta,et al.  Integrated tuberculosis and HIV care in a resource‐limited setting: experience from the Martin Preuss centre, Malawi , 2011, Tropical medicine & international health : TM & IH.

[14]  R. Zachariah,et al.  Antiretroviral treatment uptake and attrition among HIV‐positive patients with tuberculosis in Kibera, Kenya , 2011, Tropical medicine & international health : TM & IH.

[15]  R. Uehara,et al.  Evaluation of collaborative tuberculosis and human immunodeficiency virus activities in Phnom Penh, Cambodia. , 2011, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[16]  Anneke Grobler,et al.  Integration of antiretroviral therapy with tuberculosis treatment. , 2011, The New England journal of medicine.

[17]  Lerato Mohapi,et al.  Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. , 2011, The New England journal of medicine.

[18]  S. Vong,et al.  Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. , 2011, The New England journal of medicine.

[19]  J. Farrar,et al.  When to start antiretroviral therapy in HIV-associated tuberculosis. , 2011, The New England journal of medicine.

[20]  S. Lawn,et al.  Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township , 2011, BMC infectious diseases.

[21]  R. Zachariah,et al.  Retention and attrition during the preparation phase and after start of antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for programmes? , 2011, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[22]  G. Vandebriel,et al.  Evaluation of the Rapid Scale-up of Collaborative TB/HIV Activities in TB Facilities in Rwanda, 2005-2009 , 2011, BMC public health.

[23]  S. Rosen,et al.  Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review , 2011, PLoS medicine.

[24]  M. Egger,et al.  Time to Initiation of Antiretroviral Therapy Among Patients With HIV-Associated Tuberculosis in Cape Town, South Africa , 2011, Journal of acquired immune deficiency syndromes.

[25]  R. Chaisson,et al.  Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? , 2011, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[26]  L. Lynen,et al.  Evaluation of the 2007 WHO Guideline to Improve the Diagnosis of Tuberculosis in Ambulatory HIV-Positive Adults , 2011, PloS one.

[27]  V. Zweigenthal,et al.  TB and HIV integration: obstacles and possible solutions to implementation in South Africa , 2011, Tropical medicine & international health : TM & IH.

[28]  S. Lawn,et al.  Development of a Standardized Screening Rule for Tuberculosis in People Living with HIV in Resource-Constrained Settings: Individual Participant Data Meta-analysis of Observational Studies , 2011, PLoS medicine.

[29]  D. Kuritzkes,et al.  Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[30]  S. Lawn,et al.  The HIV-associated tuberculosis epidemic—when will we act? , 2010, The Lancet.

[31]  W. El-Sadr,et al.  Integration of tuberculosis and HIV services in sub-Saharan Africa: lessons learned. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  F. Varaine,et al.  Impact of introducing human immunodeficiency virus testing, treatment and care in a tuberculosis clinic in rural Kenya. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[33]  A. Hurtig,et al.  Assessing the accessibility of HIV care packages among tuberculosis patients in the Northwest Region, Cameroon , 2010, BMC public health.

[34]  W. El-Sadr,et al.  Timing of initiation of antiretroviral drugs during tuberculosis therapy. , 2010, The New England journal of medicine.

[35]  L. Lynen,et al.  Five‐year experience with scaling‐up access to antiretroviral treatment in an HIV care programme in Cambodia , 2009, Tropical medicine & international health : TM & IH.

[36]  L. Lynen,et al.  An Algorithm to Optimize Viral Load Testing in HIV-Positive Patients With Suspected First-Line Antiretroviral Therapy Failure in Cambodia , 2009, Journal of acquired immune deficiency syndromes.

[37]  S. Cole,et al.  Competing risk regression models for epidemiologic data. , 2009, American journal of epidemiology.

[38]  R. Walensky,et al.  Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa , 2009, Journal of acquired immune deficiency syndromes.

[39]  U. Lalloo,et al.  Successful Integration of Tuberculosis and HIV Treatment in Rural South Africa: The Sizonq'oba Study , 2009, Journal of acquired immune deficiency syndromes.

[40]  D. Chilton,et al.  Factors influencing delay in initiating antiretroviral therapy among HIV infected patients coinfected with tuberculosis , 2008, Thorax.

[41]  J. Odhiambo,et al.  National scale-up of HIV testing and provision of HIV care to tuberculosis patients in Kenya. , 2008, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[42]  L. Myer,et al.  Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design , 2005, AIDS.

[43]  D. Lin,et al.  Non-parametric inference for cumulative incidence functions in competing risks studies. , 1997, Statistics in medicine.

[44]  J. van Griensven,et al.  Predictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia. , 2011, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[45]  C. Allers,et al.  Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision. , 2006 .