Challenges in the integration of TB and HIV care : evidence for improving patient management and health care policy.
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Date
2016
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Abstract
TB infection remains a leading cause of morbidity and mortality among patients with HIV infection,
while HIV is the strongest risk factor for development of active TB. Integration of HIV and TB
treatment is key to reducing mortality in co-infected patients; but many obstacles stand in the way of
effective scale-up of this approach to HIV-TB treatment. The challenges associated with HIV-TB
integration extend from clinical complexities in individual patient management, to impediments in
health service organization and prioritization to address this urgent public health priority, especially in
sub-Saharan Africa where TB-HIV co-infection rates reach 80%.
The purpose of this study was to assess and identify strategies to overcome the challenges in immune
reconstitution and drug safety/tolerability when integrating HIV and TB care in a cost-effective manner
to reduce co-infection mortality.
Clinical and operational service data from the Starting Antiretroviral therapy at three Points in
Tuberculosis Treatment (SAPiT – CAPRISA 003) study, a 3-arm, randomized control trial in 642 newly
diagnosed sputum smear-positive TB-HIV co-infected adult patients with screening CD4+ cell count <
500 cells/mm3, were analysed. In addition, the incidence rate of unmasked clinical TB following ART
initiation was assessed through a retrospective chart review conducted in HIV infected patients enrolled
at the rural CAPRISA AIDS Treatment Programme.
Overall, mortality was 56% lower (RR=0.44; 95% CI: 0.25 to 0.79; P = 0.003) in patients initiated on
ART during TB treatment compared to ART deferral to after TB treatment completion. However, the
risk of immune reconstitution inflammatory syndrome (IRIS) was higher (incidence rate ratio (IRR),
2.6 (95% CI, 1.5 to 4.8); P < 0.001, in patients initiating ART within the first 2 months compared to
later ART initiation during TB treatment. In the most severely immuno-compromised patients (CD4
counts <50 cells/mm3) early ART integration was associated with an almost five-fold increased risk of
IRIS (IRR 4.7 (95% CI, 1.5 to 19.6); P = 0.004. Patients initiating ART in the first 2 months of TB
therapy had higher hospitalization rates (42% vs. 14%; P = 0.007) and longer time to resolution (70.5
vs. 29.0 days; P = 0.001) than patients in the other two groups. When assessing available evidence,
these results indicate that ART initiation in patients with CD4 cell counts >50 cells/mm3 would be most
appropriate after completion of intensive phase of TB therapy, a strategy that was found to cost $1840
per patient treated. Among HIV infected patients initially screening negative for TB there was a fourfold
higher incidence rate of unmasking TB in the first 3 months after ART initiation, compared to the
subsequent 21 months post-ART initiation. The new information generated by this study provides important evidence for policy and clinical
management of patients with HIV and TB co-infection. Firstly, careful clinical vigilance for ‘unmasked’
TB is required in patients initiating ART. Secondly, the survival benefit of AIDS therapy in TB patients
can be maximized by initiating ART as soon as possible after TB therapy has been started in patients
with advanced immunosuppression, i.e., those with CD4+ counts <50 cells/mm3. However, patients
with higher CD4+ cell counts should delay ART initiation to at least 8 weeks after the start of TB
therapy to minimize the incidence and duration of immune reconstitution disease and consequent
hospitalization. Thirdly, this approach, which is at variance with current World Health Organization
policy and guidelines, is cost-effective and readily implementable within the clinical setting. Finally,
addressing the operational challenges to HIV-TB treatment integration can improve patient outcomes
with substantial public health by reducing mortality by the most important causes of death in South
Africa.
Description
Doctor of Philosophy in Public Health Medicine. University of KwaZulu-Natal, Medical School 2015.
Keywords
Tuberculosis -- Complications., Medical policy., Tuberculosis -- Epidemiology., HIV infections -- Epidemiology., HIV infections -- Treatment., Tuberculosis -- Treatment., Theses -- Public health medicine.