Much of the discussion related to the above statements emphasized the importance of a comprehensive approach. Elaboration on the costs of a comprehensive package are presented below.
It addition to the studies described with respect to Statement 8, another noteworthy study was that conducted by Marseille et al. (2006) undertaking cost-benefit analysis of three interventions to treat HIV-infected employees in Kampala, Uganda. The costs and benefits of each intervention were compared with no intervention and with each other: cotrimoxazole prophylaxis (CTX) starting at WHO stage 2; highly active antiretroviral therapy (HAART) plus CTX starting at WHO stage 2; and a 'hybrid' strategy that begins with CTX at WHO stage 2 and later includes HAART. The 5-year health and economic outcomes were calculated using a Markov model. Inputs for disease progression rates and effects of HIV on company costs were derived from published and unpublished data and a survey administered to company officers. The analysis showed that the 'hybrid' intervention is the most cost-effective. For 100 skilled employees it would save the company 38,939 US dollars and 73 disability adjusted life-years. For unskilled workers 'CTX' is the most cost effective and would save $16,417 US dollars and 60 disability adjusted life-years. 'Hybrid' has an incremental cost-effectiveness ratio of $45 US dollars per disability adjusted life-years for unskilled workers whereas HAART is far less economical at an incremental cost per disability adjusted life-years of $4118 US dollars. For 'CTX', net savings are preserved across the full range of input values. Governments and other donors may find opportunities to share costs with the private sector as part of their phase-in strategy for antiretroviral therapy.
Badri et al. (2001) studied the effect of prophylactic low dose co-trimoxazole (480 mg per day or 960 mg three times per week) on survival and morbidity in patients in Cape Town, South Africa, stratified by WHO clinical stage, CD4 T-lymphocyte count or TLC. Patients receiving antiretroviral therapy were excluded from this study. They found that co-trimoxazole reduced mortality [adjusted hazard ratio (AHR), 0.56; 95% confidence interval (CI), 0.33-0.85;P > 0.001] and the incidence of severe HIV-related illnesses (AHR, 0.52; 95% CI, 0.38-0.68;P < 0.001) in patients with evidence of advanced immune suppression on clinical (WHO stages 3 and 4) or laboratory assessment (TLC < 1250 x 106/l or CD4 count < 200 x 106/l). No significant evidence of efficacy was found in patients with WHO stage 2 or CD4 count 200-500 x 106/l/TLC 1250-2000 x 106/l. The authors also concluded that had they applied the WHO/UNAIDS recommendations, 88.3% of their patients would have received co-trimoxazole prophylaxis at their initial clinic visit.
There is also considerable evidence to support the provision of IPT to HIV positive healthcare workers. (eg. Bucher et al. 1999, Bell et al. 1999, Hawken et al. 1999) The meta-analysis of randomized controlled trials conducted by Bucher, Griffith, Guyatt, and colleagues in 1999 examined the effectiveness of isoniazid prophylaxis for TB in HIV infection. The results compiled showed by pooling all seven trials, that a risk ratio was found for persons treated with isoniazid for developing TB of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of TB was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). The authors concluded that prophylaxis with isoniazid reduces the risk of TB in persons with HIV infection.
The literature shows the effectiveness as well as benefit and indeed cost-benefit of providing co-trimoxazole, and there seems to be consensus that the correct regimen should be based on balancing the side-effects of over-treating with the benefits in terms of decreased morbidity and mortality of the drug regime adopted, on a case-by-case basis.
According to the WHO and UNAIDS, Co-trimoxazole preventive therapy should be promoted for the prevention of several secondary bacterial and parasitic infections. TB patients are eligible for this therapy. Evidence from randomized controlled trials of co-trimoxazole preventive therapy has shown reduced mortality among HIV-positive smear-positive TB patients (Wiktor et al.,, 1999) and reduced hospitalization and morbidity among people living with HIV/AIDS (Alglaret et al.,, 1999). Other non-randomized and operational studies showed that co-trimoxazole preventive therapy is feasible (Zachariah et al.,, 2001 & 2002), safe (Zachariah 2002) and reduces mortality rates in TB patients (Zachariah et al.,, 2001, 2002 & 2003). It should be noted that one randomized control trial showed no beneficial effect of this therapy (Maynart 2001). This lack of effect was attributed to the inadequate power of the study (Godfrey-Faussett 2003). The resistance rates to co-trimoxazole among common pathogens may also be high in some settings and this may compromise the efficacy of co-trimoxazole preventive therapy (Godfrey-Faussett 2003).
The GG stressed the following points in implementing this recommendation:
- Evidence-based advocacy is required for IPT. In other words, the evidence of the effectiveness of IPT should be made widely known
- Capacity must be improved for TB screening and exclusion of active TB (i.e. new symptom screening algorithms).
- Policies specific to IPT should be established at the regional level.
- Adequate resources must be allocated to ensure availability of CTX and IP.
- The balance in choosing the correct regimen should be based on balancing the side-effects of over-treating with the benefits in terms of decreased morbidity and mortality of the drug regime adopted.
- TB and HIV programmes should establish a system to provide co-trimoxazole preventive therapy to eligible people living with HIV who have active TB.