Our experience demonstrates that integrated TB/HIV care is feasible at a rural, public MoH hospital in Kenya. Our integrated clinic, staffed primarily by clinical officers and nurses with backup assistance by medical officers and consultants, successfully administered TB and ART care with acceptable TB treatment success frequencies that improved over time. Overall mortality was low in the TB/HIV clinic for both adult and pediatric patients. However, lost-to-followup frequencies were high and occurred early in care, particularly in those presenting with advanced HIV. Many of these patients lost to followup likely account for additional deaths. Our data suggest that achieving Kenyan national TB targets of 85% cure and 90% treatment completion rates regardless of HIV status can only be achieved if loss to followup is aggressively and promptly addressed.
Proportions of patients lost to followup improved from 36% in year 1 to 12.5% in year 5. Interventions employed by the TB/HIV clinic felt to have been beneficial in improving loss to followup rates include (1) early and continuous patient education regarding both TB and HIV therapies by both clinic staff as well as persons living with HIV/AIDS; (2) effort to rapidly identify patients who miss appointments with the use of “tracers” who use village maps obtained with patient permission upon clinic enrollment; (3) use of treatment partners and directly observed therapy (DOT). However, additional qualitative research is required to understand why patients disengage with health care, and innovative solutions are urgently required.
In parallel with the declining loss to follow-up, treatment success rose and death rates fell over time. One may speculate that these improvements reflect an increased experience and competency in managing well-described complications of TB/HIV treatments including immune reconstitution syndrome, drug interactions, and comorbidities in addition to increased attention to adherence and earlier treatment for patients with lower CD4+ T-cell counts as newer guidelines appeared [4
]. Given the Kericho District Hospital served as a regional hospital and was the first to provide comprehensive HIV services in the region, outcomes observed may also reflect a referral bias, which became less pronounced over time as other facilities became available and decentralization of services occurred.
We found baseline CD4+ T-cell count highly associated with treatment success. Patients with lower CD4 counts most in need of ART were less likely to achieve treatment success compared to those with higher CD4 counts, although treatment success improved over time. These findings underscore challenges in implementing early ART in patients with advanced immunosuppression and achieving results seen in recent clinical trials [14
]. Challenges of introducing ART early during TB intensive phase treatment in patients with advanced immunosuppression in resource-limited areas are profound, and differences in outcomes observed in clinical trial versus clinical care settings well described in the resource-rich settings are likely magnified in resource-constrained settings [31
]. Barriers to early ART are both medical (e.g., pill burden, adherence, toxicities, immune reconstitution syndrome, and comorbidities) and logistical (e.g., frequent appointments requiring travel time and costs, time away from family and work). Clinical trials are better resourced to address these medical and logistical issues, not the case in resource-constrained health care systems. Innovation will be critical in solving these challenges.
Hospitalization, while theoretically practical for profoundly immunosuppressed patients who are initiating both TB treatment and ART, may often not be possible or ideal. The lack of strong infection control programs within hospitals in sub-Saharan Africa resulting in nosocomial TB transmission raises a cautionary note [32
]. The risk of hospitalization with poor infection control is particularly problematic in areas such as Kenya where TB drug susceptibility data is lacking. Congregation of the most vulnerable (i.e., those with CD4+ T-cell count <50
) with those with unknown rates of multidrug or extensively drug resistant TB has led to devastating consequences in South African settings [32
]. Hospitalization to overcome challenges and logistical issues of TB/HIV treatments must therefore be initiated with programmatic interventions that can reduce risk.
“Know your status” campaigns combined with aggressive community-based TB case finding campaigns will offer long-term solutions [4
]. The former will avoid discovery of the HIV patient presenting late into care with a low CD4+ T-cell count. The later will reduce transmission risk for all. Until those public health interventions can be broadly implemented, the integrated TB/HIV clinical service must look for solutions to translate clinical trials findings and recommendations into best practice scenarios.
Perhaps the most notable strength of the Kericho integrated TB/HIV clinic was the very early recognition of the need for integrating services (one patient, one clinic) and the institution of an integrated clinic into routine practice at a Ministry of Health facility. The most important limitation to recognize is the retrospective, uncontrolled nature of our analyses and those limitations (e.g., missing data) and biases (e.g., selection, referral, and report biases) inherent in all such secondary analyses. To that end, analyses were identified as exploratory and results are best considered hypotheses supporting or generating. While particular caution should be given to interpretations of pediatric data alone due to the low proportion of pediatric patients, we feel that a strength of the integrated TB/HIV clinic is the inclusion of pediatric patients.