1. The use of cotrimoxazole prophylaxis in the context of HIV infection
Dr. N. Kumarasamy Chief Medical Officer
YRGCARE Medical Centre
Chief-Chennai Antiviral Research and Treatment (CART) Clinical Research Site
Voluntary Health Services
Chennai, India
I would like to thank the organizers for the opportunity to discuss the new WHO Guidelines on ARV use, released earlier this year in July, and how they will enhance impact in Asian countries
On slide: Make the WHO logo bigger

2. Use of CTX prophylaxis in PLHIV
"Co-trimoxazole prophylaxis is a simple, well-tolerated and cost-effective intervention for people living with HIV. It should be implemented as an integral component of the HIV chronic care package and as a key element of pre–antiretroviral therapy care…"
"…Co-trimoxazole prophylaxis needs to continue after antiretroviral therapy is initiated until there is evidence of immune recovery ."
2006 WHO CTX Guidelines
11/11/2018

3. Implementation of CTX prophylaxis has been quite variable in countries
Significant variation and low adoption of CTX recommendations
1/3 of HIV-exposed children attending primary health care facilities in a South African did not receive CTX prophylaxis (Moodley et al, 2013).
1/3 of patients with CD4 < 200 have not received PCP prophylaxis in TAHOD cohort (Lim et al, 2012).
CTX prescribed only for 31% of patients initiating ART in Mozambique and for 80% in Kenya
Briefly recap
Lack of children studies compared to adults
Pregnancy – safety and toxicity issues
For all? Resistance issues
"…Despite the low cost, average CTX coverage was 65% for pre-ART and ART patients in Ethiopia…"
(ART costing study in Ethiopia, 2012)

4. Policy context of the CTX prophylaxis: 2006 vs 2014 scenarios
CTX use in the context of early ART initiation ("adjunctive therapy")
Expanded access to ART (but late presenters still an important group)
Impact on some associated co- morbidities in patients with less advanced or independent of HIV disease stage (eg: malaria, SBI)
HIV treatment optimization (simplification, less toxic drugs, FDCs, adherence)
As part of new WHO consolidated guidelines
2006
CTX prophylaxis used as a pre- ART care intervention
Low ART coverage/access in RLS
Major focus on patients with advanced/severe immunodeficiency
Standalone guidelines

5. CTX prophylaxis PICO questions
1) CTX initiation in HIV-infected adults (including pregnant women) starting ART
2) CTX discontinuation in HIV-infected adults (including pregnant women) during ART maintenance
3) CTX initiation in HIV infected children starting ART
4) CTX discontinuation in HIV infected children on ART
5) CTX discontinuation in HIV exposed uninfected children
6) CTX dosing (DS vs SS)
7) CTX safety during pregnancy
Major outcomes
death
new WHO stage 3 or 4 event
severe bacterial infections
severe adverse event
malaria
tuberculosis
antimicrobial treatment failure
birth outcomes
hospital admissions

6. When to Start CTX prophylaxis in adults adolescents and children: what is new?
CTX prophylaxis effective in reducing mortality, severe bacterial infections, malaria and hospitalisation in PLHIV (meta-analysis of observational studies and RCTs)
Survival benefits in children with HIV regardless of age and CD4 cell count, particularly in settings with high prevalence of malaria and/or severe bacterial infections (CHAP Trial)
Normative Trend: Expand current criteria for CTX prophylaxis initiation to all PLHIV regardless of age, CD4 cell count or WHO clinical stage in settings with high prevalence of malaria and/or severe bacterial infections.

7. When to Stop CTX prophylaxis in adults adolescents and children: what is new?
Meta-analysis of randomized clinical trials showed that continuing CTX reduces the risk of hospitalization, malaria and diarrhoea among PLHIV in settings with high prevalence of malaria and/or severe bacterial infections .
Randomized clinical trial data support the continuation of CTX prophylaxis throughout childhood, in settings with high prevalence of malaria and/or severe bacterial infections, to reduce deaths and hospitalizations (ARROW Trial)
Normative Trend: Continuation of CTX prophylaxis regardless of ART status, age, CD4 cell count or WHO clinical stage in settings with high prevalence of malaria and/or severe bacterial infections.

8. CTX prophylaxis during pregnancy
CTX prophylaxis not inferior to intermittent preventive treatment of malaria in pregnancy (IPTp) with respect to mortality, low birth weight, placental malaria, maternal deaths and severe adverse events (meta-analysis of randomized trials)
Normative Trend: Use CTX prophylaxis instead of IPTp in HIV+ pregnant women to prevent malaria in infants

9. CTX prophylaxis in HIV-exposed infants
Insufficient evidence is available to definitively establish the clinical benefit of CTX prophylaxis in HIV-exposed uninfected infants beyond the period at risk for HIV transmission
Normative Trend: Maintain the existing guidance of discontinuing CTX prophylaxis at the end of the risk period for transmission in HIV exposed uninfected infants

10. CTX prophylaxis: Some topics for research agenda
Long term safety and adherence to CTX prophylaxis (particularly in children and adolescents)
Identification of high risk groups/situations for developing CTX related severe adverse events
Surveillance of birth outcomes and defects among pregnant women on CTX prophylaxis
Surveillance on CTX resistance development in PLHIV using CTX prophylaxis

11. CTX prophylaxis: Key messages
CTX prophylaxis continue to be a feasible, well tolerated and cost effective intervention in HIV care. However, its value and use has been neglected in many settings.
New evidence showed benefits of CTX prophylaxis beyond the prevention of OIs in AIDS patients.
The high value of CTX in preventing malaria and SBI in PLHIV, (irrespective of age, clinical and immunological status) support the expansion of its use and maintenance, even in patients already on ART and with immune recovery
National HIV programmes can better implement CTX prophylaxis policy: 1) improving supply chain management, 2) reducing costs, 3) training HCWs and community and 4) better coordination with other public health programmes (malaria , MNCH and TB)

12. Acknowledgment Marco Vitoria - WHO Meg Doherty - WHO
CTX guidelines development group members