Isoniazid preventive therapy (IPT) has been recommended for people living with HIV (PLWH) since 1998 . Yet, at the end of 2013, only 21% of countries globally and 14 of 41 high-burden tuberculosis (TB)/HIV countries reported provision of IPT . The lack of IPT implementation has been driven among other by concerns regarding inadequate patient adherence potentially leading to isoniazid monoresistance . A recent review of data from trials of IPT found that adherence rates for IPT varied widely, from 34 to 98% [4–8]. To the best of our knowledge, there has been no report on IPT compliance among PLWH receiving IPT as part of comprehensive HIV care in sub-Saharan Africa.
The aim of this study was to assess IPT completion and factors associated with IPT completion among HIV-infected children and adults receiving it as part of their routine HIV care in two clinics (Kalembe Lembe and Bomoi) in Kinshasa, Democratic Republic of Congo (DRC). Clinical procedures in the two clinics have been reported elsewhere [9,10].
Starting in April 2012, patients receiving care in those clinics were screened at each visit for TB symptoms. Active TB was ruled out in adults if they did not have any of current cough, night sweats, fever, and weight loss, and in children if they did not have any of poor weight gain, fever, current cough, or contact history with a TB case . In August 2012, the two clinics started providing IPT according to WHO guidelines to all HIV-infected patients 1 year or older in whom active TB was ruled out for a minimum of 6 months, irrespective of previous TB or antiretroviral therapy (ART) history.
The main outcome in this analysis was IPT completion. All patients recorded to have stopped taking IPT with the reason for stopping recorded as ‘treatment completion’ were classified as having completed their treatment. If they had been on IPT for at least 6 months, but were not recorded as ‘treatment completion’, they were classified as not completed. Patients in whom IPT was stopped before 6 months were classified as not completed, regardless of the reason for stopping.
Bivariate and multivariate logistic regression models were used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between baseline predictors and IPT completion. All analyses were done separately for children (15 years or younger at IPT initiation) and adults (over 15 years at IPT initiation). All analyses were performed using SAS 9.3 (Cary, North Carolina, USA).
Between 1 September 2012 and 15 June 2013, 3053 PLWH receiving care in the two clinics had at least one clinic visit. Of those, 2366 were not symptomatic, and 2078 (87.8%) were initiated on IPT. This included 546 children (26.3%) and 1532 adults (73.7%) (Fig. 1, supplemental material, http://links.lww.com/QAD/A743).
Among the 546 children initiated on IPT, the median age was 8.0 years [interquartile range (IQR) 4.6, 11.2]. They had been in care for a median of 39.3 months (IQR 4.6, 11.2), and over 90% (n = 494) were on ART (Table 1). Overall, 470 (86.1%) had an IPT outcome (termination date and reason recorded: n = 431) or had been on treatment for more than 6 months (n = 39). Of those, 408 (86.8%) completed their IPT. Children on ART at IPT initiation were more likely to complete IPT (adjusted OR 1.70, 95% CI 0.75, 3.85) (Table 2, supplemental material, http://links.lww.com/QAD/A743).
Among the 1532 adults (73.7%) initiated on IPT, the median age was 35.1 (IQR 29.7, 39.8) years. They had been in care for a median of 30.5 months (IQR 15.8, 50.1), and 1218 (79.5%) were on ART (Table 1). Overall, 1280 (83.6%) had an IPT outcome (termination date and reason recorded: n = 1188) or had been on treatment for more than 6 months (n = 92). Of those 1280, 1129 (88.2%) completed their IPT. Participants on ART at IPT initiation were more likely to complete IPT than those who were not (89.2 vs. 83.3%; adjusted OR 1.54, 95% CI 1.02, 2.32). Higher age at IPT initiation was also associated with IPT completion (adjusted OR 1.02, 95% CI 1.00, 1.04) for each year increase in age (Table 2, supplemental material, http://links.lww.com/QAD/A743).
This is the first report on IPT completion among PLWH who received IPT during routine care in sub-Saharan Africa. Our results showed that among both children and adults, the proportion of patients who completed 6 months of IPT was high (>85%). This is a conservative estimate given that every participant with over 6 months of IPT without a stop date or reason recorded was treated as a failure to complete.
Our observed high proportion of PLWH who completed 6 months of IPT is the same as that observed in a TB vaccine trial in Tanzania (87%)  and in public primary HIV clinics in Brazil (85%) . A small study of IPT among pregnant women in Lesotho reported a lower proportion of IPT completion (64.5%) , probably due the high postpartum dropout that has been well documented among HIV-infected pregnant women .
Adherence to TB-preventive therapy among HIV-infected children has also been shown to be very good: 75.8% in a prospective study of ofloxacin, ethambutol, and high-dose isoniazid in South Africa  or 78.6% in a randomized trial comparing daily to thrice weekly dosing of isoniazid in South Africa .
The present study has some limitations. This is a retrospective analysis and detailed information was not always available. For example, the types and severities of reported toxicities were not recorded. Over 8% of children and 7% of adults initiated on IPT for more than 6 months lacked information in the database on whether they were still taking the treatment. Part of this might be explained by the gap between the visit to the clinic and data entry, but we have conservatively classified those patients as noncompleters.
In conclusion, in our cohort of HIV-infected children and adults receiving IPT as part of their routine HIV care and treatment, the proportion of patients completing the 6-month regimen was relatively high, and being on ART at IPT initiation was the strongest predictor of completion.
The authors thank the Centers for Disease Control and Prevention, the President's Emergency Plan for AIDS Relief, and the Global Fund to Fight AIDS, TB and Malaria for funding the HIV care in the two clinics. We thank the National TB and HIV programs of the Ministry of Health of the DRC, as well as staff at Bomoi Healthcare Center and Kalembe Lembe Pediatric Hospital, for their substantial contributions to the success of this study.
M.Y. is partially supported by a grant from NICHD (R01HD075171) and another from NIAID (U01AI096299).
Conflicts of interest
No conflicts of interest declared.
1. Godfrey-Faussett P. Policy statement on preventive therapy against tuberculosis in people living with HIV
. Geneva: World Health Organization; 1998.
2. World Health Organization. Global tuberculosis report 2014
. Geneva, Switzerland: World Health Organization; 2014.
3. Date AA, Vitoria M, Granich R, Banda M, Fox MY, Gilks C. Implementation of co-trimoxazole prophylaxis and isoniazid preventive therapy for people living with HIV
. Bull World Health Organ
4. Mwinga A, Hosp M, Godfrey-Faussett P, Quigley M, Mwaba P, Mugala BN, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia
5. Whalen CC, Johnson JL, Okwera A, Hom DL, Huebner R, Mugyenyi P, et al. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration
. N Engl J Med
6. Hawken MP, Meme HK, Elliott LC, Chakaya JM, Morris JS, Githui WA, et al. Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial
7. Souza CT, Hokerberg YH, Pacheco SJ, Rolla VC, Passos SR. Effectiveness and safety of isoniazid chemoprophylaxis for HIV-1 infected patients from Rio de Janeiro
. Mem Inst Oswaldo Cruz
8. Halsey NA, Coberly JS, Desormeaux J, Losikoff P, Atkinson J, Moulton LH, et al. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection
9. Edmonds A, Yotebieng M, Lusiama J, Matumona Y, Kitetele F, Napravnik S, et al. The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study
. PLoS Med
10. Callens SF, Shabani N, Lusiama J, Lelo P, Kitetele F, Colebunders R, et al. Mortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo
. Pediatr Infect Dis J
11. World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings
. World Health Organization
12. Munseri PJ, Talbot EA, Mtei L, Fordham von Reyn C. Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania
. Int J Tuberc Lung Dis
13. Durovni B, Cavalcante SC, Saraceni V, Vellozo V, Israel G, King BS, et al. The implementation of isoniazid preventive therapy in HIV clinics: the experience from the TB/HIV in Rio (THRio) study
2010; 24 (Suppl 5):S49–S56.
14. Tiam A, Machekano R, Gounder CR, Maama-Maime LB, Ntene-Sealiete K, Sahu M, et al. Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case for rolling out active case finding and isoniazid preventive therapy
. J Acquir Immune Defic Syndr
15. Sibanda E, Weller I, Hakim J, Cowan F. The magnitude of loss to follow-up of HIV-exposed infants along the prevention of mother-to-child HIV transmission continuum of care: a systematic review and meta-analysis
16. Seddon JA, Hesseling AC, Finlayson H, Fielding K, Cox H, Hughes J, et al. Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study
. Clin Infect Dis
17. le Roux SM, Cotton MF, Golub JE, le Roux DM, Workman L, Zar HJ. Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules
. BMC Med