HIV testing, HIV status and outcomes of treatment for tuberculosis in a major diagnosis and treatment centre in Yaounde, Cameroon: a retrospective cohort study

The study was conducted in the pneumology service of Yaounde Jamot’s Hospital (YJH). The YJH serves a referral centre for tuberculosis and respiratory diseases for the capital city of Cameroon (Yaounde) and surrounding areas as described in detail elsewhere [10]. It is one of the major centres for diagnosis and treatment of tuberculosis (CDT) in Cameroon, and YJH also host an approved treatment centre for people living with HIV infection. From year 2006 to 2011, about 1600 to 1800 patients with tuberculosis were diagnosed and treated on an annual basis in this CDT. In the year 2009, up to 11% of all cases of tuberculosis diagnosed in the country were managed at the YJH. Patients received at the CDT during January to December 2009 were considered for inclusion in the study. The study was approved by the institutional review board of the YJH.

Patients who receive care at the CDT of YJH are consecutively registered as they are started on treatment. For those with a past exposure to antituberculosis treatment, the approach is nearly similar. Patients who report back to the centre with active tuberculosis and who have been treated in the past for at least one month are registered again with a new number and started on a standardised re-treatment regimen. The following international definitions are applied: [2, 3, 9] 1) smear-positive pulmonary tuberculosis (PTB+) - acid-fast bacilli (AFB) found in at least two sputum specimens; 2) smear-negative pulmonary tuberculosis (PTB-) – persisting negativity on three sputum examinations after ten-day course of non-specific antibiotic treatment in a patient with tuberculosis-like clinical and radiological signs, and in the absence of any obvious cause; 3) extra-pulmonary tuberculosis (EPTB) – tuberculosis involving organs other than the lungs. Patients with past exposure to antituberculosis treatment are usually all smear-positive and are further classified as “relapse” (i.e. reoccurrence of the disease following a successful antituberculosis treatment course), “failure” (i.e. positive smear after five months of antituberculosis treatment) and “treatment after default” (i.e. starting antituberculosis treatment again after two consecutive months of interruption). A “new case” is a patient with tuberculosis who has never been exposed to antituberculosis treatment for more than one month in the past. “Other cases of tuberculosis” referred to patients who cannot fit in one of the categories described above.

At the CDT of the YJH, all patients with tuberculosis are screened for HIV infection free of charge after informed consent has been obtained from the patient or relative for dependant patients. This includes detection of anti-HIV 1 and anti-HIV 2 antibodies in the serum with the use of two rapid tests: Determine® HIV ½(Abbot laboratories, Tokyo, Japan) and Immunocomb® II HIV 1 and 2 Bispot (Organics, Courbevoie, France). A patient is classified as HIV positive when the two tests are positive. For discordant tests, a confirmatory western blot test (New Lav Blot, Sanofi diagnostics-Pasteur) is conducted. All HIV-positive patients are started on prophylaxis with cotrimoxazole and those with CD4 count <200/mm³ are started on highly active antiretroviral therapy free of charge. Initial antiretroviral regimens are the combinations lamivudine-zidovudine-efavirenz or lamivudine-stavudine-efavirenz.

Tuberculosis treatment at the CDT is made according to the guidelines of the Cameroon National Programme Against Tuberculosis (NPAT) and the WHO recommendations [11, 12]. Patients are either admitted during the intensive phase of antituberculosis treatment, or treated as outpatient. Antituberculosis drugs are dispensed free of charge to all patients. Treatment regimens used are standard regimens of category I for new patients and of category II for re-treatment cases. New cases are treated with a regimen that includes an intensive phase of two months duration with rifampicin (R), isoniazid (H), ethambutol (E) and pyrazinamide (Z), followed by a 4-month continuation phase with rifampicin and isoniazid (2RHEZ/4RH). During re-treatment, category I medications (R, H, E, Z) are completed with streptomycin (S). Therefore, re-treatment cases are treated with RHEZS for two months, followed by one month on RHEZ and five months on RHE (2RHEZS/1RHEZ/5RHE). During the intensive phase, adherence is directly monitored by the healthcare team for patients admitted, and during weekly drug collection in those treated as outpatients. The continuation phase is conducted on the outpatient basis and adherence assessed during monthly drugs collection visits.

During antituberculosis treatment, PTB+ patients are re-examined for AFB at the end of month 2, 5 and 6 for new cases, and at the end of month 3, 5 and 8 in case of re-treatment. PTB- and patients with EPTB are monitored clinically and/or radiologically at the same frequency. At the end of the treatment, patients are ranked into mutually exclusive categories [13] as: 1) cured – patient with negative smear at the last month of treatment and at least one of the preceding; 2) treatment completed – patient who has completed the treatment and for whom the smear result at the end of the last month is not available; 3) failure – patient with positive smear at the 5^th month or later during treatment; 4) death – death from any cause during treatment; 5) defaulter – patient who’s treatment has been interrupted for at least two consecutive months; 6) transfer – patient transferred to complete his treatment in another centre and who’s treatment outcome is unknown.

This was a retrospective cohort study among TB patients aged ≥ 15 years. Tuberculosis treatment registers and antituberculosis treatment forms of the YJH’s CDT served as basis for data collection for the study. Data were collected on age, sex, residence (urban vs. rural), history of exposure to antituberculosis treatment, localisation of tuberculosis infection, status for HIV infection, CD4 lymphocyte count (in those with HIV infection) and outcome of antituberculosis treatment. Cured and antituberculosis treatment completion were considered as favourable outcome (successful treatment) while death, default and failure were considered as unfavourable outcome [14].

Data analysis used SPSS® v.12.0.1 for Windows® (SPSS Inc., Chicago, USA) and SAS/STAT® v 9.1 for windows (SAS Institute Inc., Cary, NC, USA). Results are presented as count (proportions), means (standard deviation, SD) or median (interquartile range, IQR). Group comparisons used chi square of Fisher exact test for qualitative variables, and Student t-test or Mann-Whitney U test for quantitative variables. Multinomial Logistic regression models were used to investigate the effects of HIV testing and HIV status on the outcomes of tuberculosis in sex and age adjusted analysis, and after further adjustment for other potential confounders. A p-value < 0.05 was used to characterise statistically significant results.

During the year 2009, 1647 patients were screened and treated for tuberculosis at the Yaounde Jamot Hospital’s Centre for Diagnosis and Treatment. They were aged 33 years (interquartile range: 25-43 years) and 938 (57%) were men. Clinical forms of tuberculosis were: 1216 (73.8%) for PTB+, 155 (9.4%) for PTB- and 276 (16.8%) for PTB (Table 1).

In all, 272 (16.5%) patients were cured and 849 (51.5%) successfully completed the treatment, giving and overall treatment success rate of 68.1%. Other outcomes of care were failure (0.4%), death (5.2%), default (20.1%) and transfer (6.1%). Characteristics of participants according to the outcomes of care are described in Table 1, showing some significant differences in the distribution by residence (urban vs. rural) and clinical forms of tuberculosis.

A total 1419 (86.2%) patients were tested for HIV, and 497 (35%) were positive for HIV, all for HIV-1 subtype. Of those tested positive, 229 (46.1%) received antiretroviral therapy. Compared with those who did not test, patients who tested for HIV were borderline younger (35.3 vs. 37.0 years, p = 0.06), included more women (44.6% vs. 33.3%, p = 0.001), and more individuals with smear positive tuberculosis than with smear negative or extra-pulmonary tuberculosis (75.8%, 8%, 16.2% vs. 61.8%, 18% and 20.2%, p < 0.001). Among participants tested for HIV, patients with positive status as compared with the negative ones were older (36 vs. 30 years, p < 0.001), included more women (57.1% vs. 37.3%, p < 0.001), included fewer patients with smear positive than with smear negative and extra-pulmonary tuberculosis (67.6%, 10.3%, 22.1% vs. 80.1%, 6.8%, 13%, p < 0.001). The distribution of participants according to whether they were tested for HIV and/or whether such test was positive varied significantly across outcome of care for tuberculosis (Table 1).

In sex and age adjusted multinomial logistic regression analysis, and using the combined outcome of cure/treatment completed (treatment success) as the reference, not testing for HIV was positively and significantly associated with treatment default/failure, deaths and transferred-out (Table 2). The range of effect was similar from these 3 broad outcomes. Among those tested for HIV, a positive status was associated with an odds ratio (95% confidence interval) of 6.40 (3.57-11.46) for mortality, but had no effect on other outcomes (Table 2). Similar range of effect was observed when participants with unknown status for HIV were compared with those with negative status [6.49 (3.26-12.93)]. In sex and age adjusted analysis, age was associated with mortality, urban residence with transfer-out, and SPTB- associated with death and treatment default/failure (Table 2).

In multivariable analysis, with further adjustment for residence and clinical form of tuberculosis, associations of HIV testing and HIV status with the outcome of treatment were largely similar to those observed in age and sex adjusted analysis, with only marginal attenuation of the effect sizes (Table 3). However, the global effect of clinical form of tuberculosis on the outcome of antituberculosis treatment was no longer significant (p-value = 0.140 for the likelihood ratio test).

A subgroup of HIV positive patient (278) also had CD4 count data available. Figure 1 show the distribution of outcomes of tuberculosis care according to the stage of immune-depression in this subgroup. Mortality rate increased with decreasing CD4 count (CD4 count < 200/mm³) while treatment success was better in those with higher CD4 count (p = 0.03, Figure 1).