Treatment and Prevention of HIV Amongst Refugees and IDPs Rafik Hanna, M.D. St. Luke’s Roosevelt Hospital Center Global Health Fellowship Lecture Series

UNHCR, WHO, UNAIDS Policy Statement on HIV Testing and Counseling for Refugees and IDPs (2009) ► No mandatory or compulsory HIV testing of persons of concern to UNHCR, including children. ► Scale up access to HIV testing and counseling. ► All HIV testing and counseling of persons of concern to UNHCR should ensure that confidentiality and informed consent are ensured. ► Ensure that patients being testing have the same rights as the citizens of host countries. ► Access to HIV prevention and treatment information in a language the person can understand. ► All health care workers conducting HIV testing and counseling should be trained to obtain informed consent, ensure confidentiality, pre-test information and post-test counseling and how to recommend the test. Health care workers providing HIV testing and counseling in the context of resettlement should be informed of resettlement criteria in relation to HIV so that they can adequately inform applicants.

► “In generalized HIV epidemics, with a supportive social, policy and legal framework, HIV testing and counseling should be recommended to all persons of concern to UNHCR during contact with health care providers, in line with the guidance of the country and where this is available to the surrounding populations. A phased implementation of provider initiated HIV testing and counseling is recommended.” ► “In concentrated and low level epidemics, with a supportive social, policy and legal framework, recommendation of HIV testing and counseling should be considered in sexually transmitted infections services, services for most at risk populations, antenatal, childbirth and postpartum health services and tuberculosis services, in line with the guidance of the country and where this is recommended to the surrounding national populations.” UNHCR, WHO, UNAIDS Policy Statement on HIV Testing and Counseling for Refugees and IDPs (2009)

UNHCR, WHO, UNAIDS Policy Statement on HIV Testing and Counseling for Refugees and IDPs Precautions ► Not a priority in the very initial early stages of an emergency as it is not a life-saving intervention in the immediate term. ► It becomes an important intervention once the emergency situation stabilizes. ► Promotion of testing may increase protection issues for patients found to be HIV positive. ► Ensuring that laws, policies, and practices regarding HIV and respect for human rights before integrating provider initiated testing and counseling into existing health systems.

WHO Consensus Statement ► The minimum requirements and package of services needed to deliver ARVs for HIV prevention and treatment in emergency settings. ► Continuation of ARV therapy for those who were previously on treatment. ► Initiation of ARVs for those meeting minimal requirements. ► Mother – child prevention for HIV transmission ► Availability of PEP for healthcare workers and in rape management. ► Setting up of procurement systems that can respond to urgent ARV supply needs in emergency settings, while preventing stock piling and wastage of drugs.

Key Considerations Governing the Provision and Use of ARVs in UNHCR Operations ► Refugees often live for years in relatively stable settings in their host country. By the end of 2003, refugee populations remained in their host country for an average of 17 years. ► A minority of refugees in numerous countries are already finding their own innovative ways to begin ARVs. ► The increase of ARV resistance by stopping and then re- starting the therapy in a controlled fashion is not considered to be more of a risk for populations that have been displaced by conflict than other populations. The largest threat to developing ARV resistance remains persons taking ARVs in an incorrect manner; this threat is no larger for forcibly displaced populations than other populations (?)

Principles Governing the Provision and Use of ARVs in UNHCR Operations ► Planning for and including HIV in the earliest possible stages of an emergency response is necessary. ► Continuity of ART. ► Refugees should receive equivalent services as those available in the surrounding community. ► Interventions are to be initiated only where and once the minimum criteria to implement such activities are met. ► Diagnostic and treatment protocols should follow those of the host community unless they are ineffective. ► Sustainability of ART (minimum of one year). ► “Pilot” programs should be implemented in line with national policies.

Post-exposure Prophylaxis ► 28-day course of ARVs that reduces the likelihood of transmission after exposure to an HIV-positive source. ► Part of the response to rape and part of sexual and gender-based violence programs. ► Used within 72-hours following non-occupational exposure to HIV (usually sexual), following host country or UN guidelines. ► All occupational (e.g. needle stick) exposure in line with the UN and NGO occupational guidelines for provision of PEP.

Prevention of Mother-to-Child Transmission (PTMCT) ► PMTCT programs should be implemented for refugees as soon as feasible. ► In cases of repatriation to sites with unknown or poor access to ARVs, similar to treatment for tuberculosis, the pregnant woman and her family should be advised to delay repatriation until after delivery in order to complete PMTCT. ► If PTMCT programs exist in areas of return, cross-border programs should be established to coordinate PTMCT follow-up and referrals for those pregnant women who have been diagnosed early in pregnancy and who insist upon repatriation, in order to ensure they and their newborns receive appropriate care, treatment and follow-up. ► PMTCT programs should be as comprehensive as possible and at a minimum include comprehensive maternal-child healthcare; counseling and testing services; counseling and support about safe infant feeding practices, optimal obstetrical care practices; short-course ARVs for HIV infected pregnant women and newborn; family planning counseling and services linked to voluntary counseling and testing. Such programs must follow international standards and norms. ► Other components of PMTCT, such as long term ART and care of the mother should be considered in all PMTCT programs.

Provision of ART 1. For refugees, who had been on ART in their country of origin prior to flight, every effort should be made to secure prompt continuation of treatment: ► If ART is available in the area/district where the refugee stays, the refugee should be referred to the existing facilities without delay in order to continue ART. ► If ART is not available in the area/district, action should be taken without delay to either move the refugee and his/her family to a suitable location where treatment is possible or to bring services to the concerned area in a concerted effort involving UNHCR, the HIV UN Theme Group (of which UNHCR is a member), the host Government, and NGOs.

Provision of ART 2. For refugees, who did not receive ART prior to their flight, at a minimum, ART should be provided when such treatment is available to surrounding populations.

Provision of ART 3. In situations where voluntary repatriation is considered imminent the following considerations should govern the decision to commence ART: following considerations should govern the decision to commence ART: ► ART is a lifesaving treatment and should be considered for refugees regardless of whether repatriation is imminent. ► If ART is already available in the country of origin and accessible upon return, there is no reason to abstain from or delay the start of ART. However, measures to secure the continuity of treatment of returnees under ART must form an integral component of the planning of the repatriation operation. ► It must be agreed that in exercise of their freedom of movement, returnees should be allowed and assisted to return to areas where continuation of ART can be secured. ► UNHCR with UN HIV Theme Group, NGOs, and governments must work to ensure that there is good communication and strong linkages with national programs in both countries (or with other organizations if governments are not providing ART to these populations). These interventions should preferably be an integral part of the health systems and not be parallel programs. ► Issues such as ART protocols, adherence and other key factors need to be considered beforehand, hence the need for regional/subregional initiatives that can harmonize drug and treatment protocols.

Provision of ART 4. If ART is not and cannot promptly be made available within the country of origin upon return, the refugee should be informed about country of origin upon return, the refugee should be informed about this fact and receive comprehensive counseling on the medical this fact and receive comprehensive counseling on the medical situation and on the options available for him or her, including on the situation and on the options available for him or her, including on the possibilities to (temporarily) remain in the country of asylum, thereby possibilities to (temporarily) remain in the country of asylum, thereby allowing him or her to make an informed decision: allowing him or her to make an informed decision: ► If a refugee does not wish to repatriate because lifesaving medicine is not available upon return, UNHCR, respecting the voluntary nature of repatriation, cannot actively be engaged in returning the individual and must take the utmost efforts to advocate for this person to be permitted to stay in the country of asylum on humanitarian grounds until sufficient medical services will be established in the country of origin. ► During that time, UNHCR, UN HIV theme Group, and other organizations should advocate for and aid in the coordination of ART to be available in the country of origin and in particular in areas to where the repatriates return.

Provision of ART 5. Where a refugee is already on ART and insists on voluntary repatriation, although ART is not and cannot promptly be made available upon return within the country of origin, proper counseling must ensure that the refugee fully understands the medical consequences of discontinuing the treatment. This counseling and the informed decision of the refugee must be properly documented.

WHO Clinical Staging of HIV ► Staging is based on clinical findings that guide the diagnosis, evaluation, and management of HIV/AIDS. ► Does not require a CD4 count or VL. ► Used to determine eligibility for ARV therapy in settings where CD4 testing is not available. ► Used for ≥15 years of age. ► Last revised in 2007.

WHO Clinical Staging of HIV ► Primary HIV infection (asymptomatic or acute retroviral syndrome) 1. Clinical Stage I: asymptomatic or persistent generalized lymphadenopathy. 2. Clinical Stage II: moderate unexplained weight loss (<10% of presumed or measured body weight), recurrent respiratory infections (sinusitis, tonsillitis, otitis media, and pharyngitis), herpes zoster, angular cheilitis, recurrent oral ulceration, papular pruritic eruptions, seborrheic dermatitis, fungal nail infections.

WHO Clinical Staging of HIV 3. Clinical Stage III: unexplained severe weight loss (>10% of presumed or measured body weight), unexplained chronic diarrhea for >1 month, unexplained persistent fever for >1 month (>37.6ºC, intermittent or constant), persistent oral candidiasis (thrush), oral hairy leukoplakia, pulmonary tuberculosis (current), severe presumed bacterial infections (e.g., pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia), acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis unexplained anemia (hemoglobin 10% of presumed or measured body weight), unexplained chronic diarrhea for >1 month, unexplained persistent fever for >1 month (>37.6ºC, intermittent or constant), persistent oral candidiasis (thrush), oral hairy leukoplakia, pulmonary tuberculosis (current), severe presumed bacterial infections (e.g., pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia), acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis unexplained anemia (hemoglobin <8 g/dL), neutropenia (neutrophils <500 cells/µL), chronic thrombocytopenia (platelets <50,000 cells/µL).

WHO Clinical Staging of HIV 4. Clinical Stage IV : HIV wasting syndrome, as defined by the CDC (see Table 1, above), pneumocystis pneumonia, recurrent severe bacterial pneumonia, chronic herpes simplex infection (orolabial, genital, or anorectal site for >1 month or visceral herpes at any site), esophageal candidiasis (or candidiasis of trachea, bronchi, or lungs), extrapulmonary tuberculosis, Kaposi sarcoma, cytomegalovirus infection (retinitis or infection of other organs), central nervous system toxoplasmosis, HIV encephalopathy, cryptococcosis, extrapulmonary (including meningitis), disseminated nontuberculosis mycobacteria infection, progressive multifocal leukoencephalopathy, candida of the trachea, bronchi, or lungs, chronic cryptosporidiosis (with diarrhea), chronic isosporiasis, disseminated mycosis (e.g., histoplasmosis, coccidioidomycosis, penicilliosis), recurrent nontyphoidal Salmonella bacteremia, lymphoma (cerebral or B-cell non-Hodgkin), invasive cervical carcinoma, atypical disseminated leishmaniasis, symptomatic HIV-associated nephropathy, symptomatic HIV-associated cardiomyopathy, reactivation of American trypanosomiasis (meningoencephalitis or myocarditis) HIV wasting syndrome, as defined by the CDC (see Table 1, above), pneumocystis pneumonia, recurrent severe bacterial pneumonia, chronic herpes simplex infection (orolabial, genital, or anorectal site for >1 month or visceral herpes at any site), esophageal candidiasis (or candidiasis of trachea, bronchi, or lungs), extrapulmonary tuberculosis, Kaposi sarcoma, cytomegalovirus infection (retinitis or infection of other organs), central nervous system toxoplasmosis, HIV encephalopathy, cryptococcosis, extrapulmonary (including meningitis), disseminated nontuberculosis mycobacteria infection, progressive multifocal leukoencephalopathy, candida of the trachea, bronchi, or lungs, chronic cryptosporidiosis (with diarrhea), chronic isosporiasis, disseminated mycosis (e.g., histoplasmosis, coccidioidomycosis, penicilliosis), recurrent nontyphoidal Salmonella bacteremia, lymphoma (cerebral or B-cell non-Hodgkin), invasive cervical carcinoma, atypical disseminated leishmaniasis, symptomatic HIV-associated nephropathy, symptomatic HIV-associated cardiomyopathy, reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)Table 1Table 1

WHO Clinical Staging of HIV ► 2010 – Stage IV: treat; Stage III: treat; stage II: treat if symptomatic; stage I: do not treat. If known CD4 < 350: treat. ► Validation of World Health Organization HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda. Baveewo S, Ssali F, Karamagi C, Kalyango JN, Hahn JA, et al PLoS ONE 6(5): e doi: /journal.pone ► Previous sensitivities in Uganda at CD4 of 200 was 51-52% and specificity was 68-88%.

WHO Clinical Staging of HIV

WHO 2010 Recommendations on ARV Therapy

HIV Treatment and the Challenge of IDPs if Movement is Imminent ► ART is a long-term life-saving measure and should still be evaluated. ► Displaced persons may be returning to areas where HIV care is stronger or weaker or even non-existent. ► Staging of the disease and anticipated availability at the site being travelled to should guide the urgency of therapy initiation. ► If patients have advanced clinical disease (severe AIDS-defining illness or CD4<50), patients should be advised to delay their departure and ART commenced immediately.

HIV Treatment and the Challenge of IDPs if Movement is Imminent ► If the patient is WHO Class III and healthy or with a good known CD4 and: 1.treatment is available at the site being travelled to, then initiation of treatment may occur at either location. 2.treatment is not available at the site being travelled to, the displaced person should be encouraged to remain where they are and initiate ART for at least 3 months to monitor potential side- effects and adherence, and subsequently be provided with a stock of medication for 3-6 months if possible. 3.individuals insist on leaving immediately or in the near future, then the options include a) leaving with no ART, b) initiation of ART for a short period prior to leaving together with additional ART stock, or c) leaving with a supply to be initiated at the site being travelled to (with referral letters and extensive pre- adherence counseling). *The guidelines group believed option a to be better for most individuals going to areas of limited care and options b or c for individuals going to areas of adequate care.

HIV Treatment and the Challenge of IDPs if Movement is Imminent ► There may be additional reasons for delaying treatment initiation, other than those previously listed, such as patient readiness, practical considerations (such as side effects during travel and reintegration), concurrent medical conditions that may worsen on ART (e.g. immune reconstitution diseases may present catastrophically and the receiving site may not have the resources to manage them), and other considerations. The risks and benefits of deferring treatment must be carefully weighed against immediate initiation; options should be discussed with the patient, including delaying departure. ► This decision-making may require significant ART expertise, and the health worker should consult if not confident that s/he has the expertise to give adequate counsel. ► Choice of regimen: In general, try to match the regimen to the one the individual is most likely to be on over the next year (try wherever possible to match the regimen to that available in the area the person is going to).

HIV Treatment and the Challenge of IDPs

Treatment for Patients on Previous ARTs ► A repeat HIV test to confirm their infection. ► If the individual is currently on ART, continue treatment with no interruption. ► If possible, a viral load and CD4 count should be done at the time of the first visit. If the VL is raised (according to the national protocol), adherence intensification is usually warranted. Expert opinion should be sought before ordering resistance testing, if available. ► If there has been a treatment interruption, try to restart treatment as soon as possible, after careful assessment of the reasons for the interruption. The VL may be high if the interruption is significant. ► Adherence counseling and support should be undertaken in light of the new circumstances.

Treatment for Patients on Previous ARTs ► If on the same regimen as national program, then continue same regimen. ► If currently on a different regimen from the national program, continue with the current regimen if the national program supports this different regimen. ► If the national program does not support the current regimen, then decide based on the history of side effects and co-morbidities, history of treatment or clinical failure, use of concomitant medication. ► If patient on previous unknown regimen or poor known history, then initiate on the national guidelines first-line therapy and follow closely. Check a VL in 6 weeks if possible.

Treatment for Patients on ARTs and Contingency Planning ► Though not less likely to be adherent when on medications, displaced persons are at a greater risk of treatment interruption. ► Provisions of personal ART stocks. ► Patients should have in their position a personal HIV treatment card (drugs, labs, toxicities, illness history). ► If on an NNRTI regimen (which have a long half-life) and treatment is stopped with no possibility of immediate restocking of drugs, consider “covering the tail” (the long half-life of NNRTIs) by continuing dual nucleosides for a week after stopping the NNRTI, to prevent possible NNRTI resistance.

ART Specific Challenges ► Some ARVs (e.g. ritonivir) require refrigeration. ► Some ARVs require food intake for optimal absorption. Many regimens require twice daily dosing. Displaced persons may not have sufficient food available and should be told to take their medications despite lack of food, and warned of possible increased GI side-effects. ► If the ART choice requires more frequent monitoring, consider the ease and cost of access to the displaced person. ► ARVs requiring reconstitution (some pediatric formulations) depend on access to clean water, which may not be easily available to displaced persons. ► Lack of lab access should not exclude ART for patients. If the ART choice requires more frequent monitoring, consider ease and cost of access. For example, a nevirapine regimen should ideally have liver function monitoring in the initiation phase, which may increase the frequency and cost of visits. However, in many cases, nevirapine is the only NNRTI available, and no liver function testing is available, in which case the drug should be initiated with extensive patient counseling. ► Syrup formulations are often difficult to carry and require a lot of space.

Evidence Based Guidelines for Immigrants and Refugees Canadian Medical Association Journal ► Screen for HIV, with informed consent, all adolescents and adults from countries where HIV is prevalent (> 1%) – Sub- Saharan Africa and parts of the Caribbean (The HIV infection rate is about 12.6 times higher among immigrants and refugees from countries where HIV is endemic than it is in the Canadian-born population.) ► The decision to screen men and women is based on the dramatic reduction in mortality with ARV (triple) therapy.

Bibliography ► UNHCR/WHO/UNAIDS Policy Statement on HIV Testing and Counselling in Health Facilities for Refugees, Internally Displaced Persons and other Persons of Concern to UNHCR ► WHO Consensus Statement – Delivering Antiretroviral Drugs in Emergencies: Neglected but Feasible 9/20/2006. ► UNHCR Antiretroviral Medication Policy for Refugees January, ► WHO Case Definitions of HIV For Surveillance and Revised Clinical Staging and Immunological Classification of HIV-Related Disease in Adults and Children ► WHO Antiretroviral Therapy For HIV Infection in Adults and Adolescents 2006 Revision. ► WHO Antiretroviral Therapy For HIV Infection in Adults and Adolescents 2010 Revision. ► UNHCR Clinical Guidelines For Antiretroviral Therapy Management For Displaced Populations ► Validation of World Health Organization HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda. Baveewo S, Ssali F, Karamagi C, Kalyango JN, Hahn JA, et al PLoS ONE 6(5): e doi: /journal.pone ► Evidence Based Clinical Guidelines for Immigrants and Refugees. on July 27, P.35-37