Hermans SM, Castelnuovo B, Katabira C, Mbidde P, Lange JM, Hoepelman AI, Coutinho A, Manabe YC. 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. J Acquir Immune Defic Syndr. 2012 Jun 1;60(2):e29-35.
To determine whether integrated care for HIV infection and tuberculosis (TB) would result in improved TB treatment outcomes and prompt initiation of antiretroviral therapy (ART) by eligible patients.
A large urban HIV clinic in Kampala, Uganda.
Retrospective cohort study with pre- and post-intervention evaluation.
All patients initiating TB treatment at the clinic in 2007 (n=346) and 2009 (n=366). In both years, mean patient age was about 37, and about half the patients were female. In 2007, about 70% of patients were ART-naïve; in 2009 about 63% were ART-naïve.
TB outcomes: World Health Organization (WHO)-defined TB cure, completion, death, default, transfer-out and treatment failure.(1) HIV outcomes: proportion, timing and outcomes of ART initiation in ART-naïve TB patients.
Uganda Ministry of Health ART guidelines(2) were followed. Patients were started on ART if they had WHO Stage IV disease(3) or CD4 <250 µL. The CD4 threshold for ART initiation in HIV-infected patients with active TB was 350 mm3. ART was initiated during the intense phase of treatment in TB patients with CD4 <200 µL. All patients received cotrimoxazole prophylaxis, regardless of CD4 count. New TB cases were treated with a combination of rifampicin, isoniazid, ethambutol, and pyrazinamide (RHZE) in a 2-month intensive phase, after which they were treated in a 6-month continuation phase with isoniazid and ethambutol. In retreatment cases, streptomycin was added to the 2-month intensive phase. This was followed by a month of RHZE, and then a 5-month continuation phase with rifampicin, isoniazid, and ethambutol. Patients visited the clinic every 4 weeks. Researchers gathered routine data on clinical parameters, ART, adherence, WHO disease stage, toxicities, and opportunistic infections.
A separate new integrated clinic for TB and HIV services was established in December 2008. All data gathered in 2009 were compared to all data gathered in 2007. Proportions and medians of 2007 outcomes and 2009 outcomes were compared using Χ2 and 2-sample Wilcoxon rank-sum tests, respectively. Time to ART initiation was analyzed using Kaplan-Meier survival curve analyses, which were generated and compared using the log-rank test. All statistical tests were 2-sided at an a value of 0.05.
A total of 346 HIV-infected patients began TB treatment in 2007 and 366 in 2009. Patients from 2009 had more extrapulmonary TB and were likely to be on ART at TB diagnosis. More patients who began TB treatment in 2009 (251, 68%) completed therapy than those who began it in 2007 (215, 62%) (p<0.001); the proportion that defaulted decreased during this time from 30% to 10%.
Of the patients who began ART, more were started during TB therapy (as opposed to after completing TB therapy) in 2009 than in 2007 (94% vs. 78%, p<0.001), and the median time between initiation of TB therapy and initiation of ART decreased from 103 days to 45 days. This difference was most pronounced in patients with ≤100 CD4 cells/µL.
The authors found that integrating HIV and TB care in their clinic led to better TB treatment outcomes and earlier and more prioritized initiation of ART. They suggest that a fully integrated model of TB/HIV service delivery should be implemented in settings with a high prevalence of HIV and TB.
Apart from what seems to be a minor error in characterizing the results for one outcome, the overall risk of bias in this study is low. Using a nine-point scale to assess the study rigor, this study received seven points. The study design included pre/post intervention data; it included a comparison group; it included a cohort; the comparison groups were equivalent socio-demographically and at baseline on outcome measures. The authors conducted statistical tests to control for potential confounders in the analysis. The study's follow-up rate was well over the rigor scale's specification of 75%. The study protocol was not available for evaluation of outcome reporting.
WHO released an "Interim Policy on TB/HIV Activities" in 2004, which articulated objectives of establishing mechanisms for collaboration between tuberculosis and HIV/AIDS programs, decreasing the burden of tuberculosis in people living with HIV/AIDS, and decreasing the burden of HIV in tuberculosis patients.(4) WHO's "Global Plan to Stop TB" calls for TB/HIV services to be provided as part of an integrated package of care, offered at the same time and place to the degree this is possible.(5) While a recent systematic review of 63 peer-reviewed articles and 70 conference abstracts identified five models for integration of TB/HIV services,(6) the review identifies only four studies providing evidence on the impact of integrated service delivery on patient-important treatment outcomes.(7, 8, 9,10) Hermans and colleagues identify two additional studies(11, 12) and suggest that theirs is the first to provide evidence on the impact of integrated TB/HIV services on ART prescribing behavior and the timing of ART initiation. WHO will release new guidelines in 2013 on HIV treatment optimization and service delivery, which will also include guidance on TB/HIV service integration.
TB/HIV services should be delivered together, as an integrated package of care. Controlled studies and cluster-randomized trials are needed to provide additional evidence on the efficacy of integrated TB/HIV services in improving treatment outcomes and to identify the best models for providing these services in specific local contexts.
- World Health Organization (WHO). Treatment of Tuberculosis Guidelines. [Accessed 11 June 2012]
- Uganda Ministry of Health. National Antiretroviral Treatment and Care Guidelines for Adults, Adolescents, and Children. [Accessed 11 June 2012]
- World Health Organization (WHO). WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children (2006). [Accessed 11 June 2012]
- WHO. Interim policy on collaborative TB/HIV activities. Geneva: World Health Organisation; 2004. [Accessed 14 June 2012].
- WHO/Stop TB Partnership. Global Plan to Stop TB (2011-2015). [Accessed 14 June 2012].
- Legido-Quigley H, Montgomery C, Khan PY, et al. >Integrating tuberculosis and HIV services in low- and middle- income countries: a systematic review. Background paper for the First Global Symposium on Health Systems Research, 16-19 November 2010, Montreux, Switzerland. Available from: firstname.lastname@example.org (also in press, Trop Med Int Health 2012)
- Burua A, Musisi A, Tumwesigye B, Kirunda I, Pacutho E, Muhwezi A, et al. The Integration of Tuberculosis HIV/AIDS Care in 89 Health Facilities in Uganda [Abstract no. 554]. HIV/AIDS Implementers' Meeting. Kampala, Uganda; 2008.
- Harris JB, Hatwiinda SM, Randels KM, Chi BH, Kancheya NG, Jham MA, et al. Early lessons from the integration of tuberculosis and HIV services in primary care centers in Lusaka, Zambia. Int J Tuberc Lung Dis. 2008;1 (7):773-9.
- Chan A, Njala J, Kanyerere H, van Lettow M. Improved uptake of antiretroviral therapy (ART) following integration of TB and HIV services in a district in southern Malawi [Abstract no. CDD062]. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa; 2009.
- Piyaworawong S, Yanai H, Nedsuwan S, Akarasewi P, Moolphate S, Sawanpanyalert P. Tuberculosis preventative therapy as part of a care package for people living with HIV in a district of Thailand. AIDS. 2001;15(13):1739-41.
- Huerga H, Spillane H, Guerrero W, et al. Impact of introducing human immunodeficiency virus testing, treatment and care in a tuberculosis clinic in rural Kenya. Int J Tuberc Lung Dis. 2010;14:611-615.
- Phiri S, Khan PY, Grant AD, et al. Integrated tuberculosis and HIV care in a resource-limited setting: experience from the Martin Preusscentre, Malawi. Trop Med Int Health. 2011. doi: 10.1111/j.1365-3156.2011.02848.