NATIONAL AIDS CONTROL PROGRAMME (NACP) PHASE II Initiatives B: care: Low cost care and support (a) Prevention

n of parent to child transmission (b) Management of HIV-TB co infection (c) Treatment of opportunistic infection (d) Piloting ART (e) Post exposure prophylaxis

(a) PREVENTION OF PARENT TO CHILD TRANSMISSION The Prevention of Parent to Child Transmission of HIV/AIDS (PPTCT) programme was started in the country in the year 2002 following a feasibility study in 11 major hospitals in the five high HIV prevalence states. Currently, there are more than 4000 Integrated Counselling and Testing Centres (ICTCs) in the country, most of these in government hospitals, which offer PPTCT services to pregnant women. Of these ICTCs , 502 are located in Obstetrics and Gynaecology Departments and in Maternity Homes where the client load is predominantly comprised of pregnant women. The Joint Technical Mission on PPTCT (2006) estimated that out of 27 million annual pregnancies in India, 189,000 occur in HIV positive pregnant women. In the absence of any intervention, an estimated cohort of 56,700 infected babies will be born annually. The PPTCT programme aims to prevent the perinatal transmission of HIV from an HIV infected pregnant mother to her newborn baby. The programme entails counselling and testing of pregnant women in the ICTCs. Pregnant women who are found to be HIV positive are given a single dose of Nevirapine at the time of labour; their newborn babies also get a single dose of Nevirapine immediately after birth so as to prevent transmission of HIV from mother to child. The PPTCT services cover about 10 per cent pregnancies in the country. In the year 2006, 2.1 million pregnant women accessed this service. Of these, more than 16,500 pregnant women were HIV positive. In order to provide universal access to these services further scale up is planned up to the level of Community Health Centre and the Primary Health Centre, as well as private sector by forging public-private partnerships. Through these measures NACO hopes to achieve the UNGASS target of reducing the proportion of infants infected with HIV/AIDS by 50 percent by 2010

(b) MANAGEMENT OF HIV-TB CO- INFECTION Tuberculosis has been a major public health problem for centuries. The implementation of effective public health interventions for the prevention and control of TB has significantly contributed to a substantial reduction of the global disease burden. However, the emergence of the HIV epidemic has posed major challenges to TB control efforts globally. In a country with almost 40% of population already infected with TB, an increasing prevalence of HIV will jeopardize TB control efforts with serious consequences. In India, there were an estimated 3.97 million people living with HIV at the end of year 2001(TB figures). There exist a synergistic relationship between tuberculosis and HIV. Impact of HIV on TB are: 1. About a third of the HIV population, world wide, is coinfected with M. TB. 2. HIV epidemic has the potential to worsen the TB epidemic as has happened in certain African countries. This is mainly because HIV increases the risk of disease reactivation in people with latent TB and because HIV infected persons are more susceptible to new TB infection. 3. An HIV positive person infected with M. tuberculosis has a 50% lifetime risk of developing TB whereas an HIV negative person infected with M. tuberculosis has only a 10% risk of developing TB. This is especially important in India where it is estimated that 40% of the adult population harbors M. tuberculosis. 4. TB is the most common serious opportunistic infection occurring among HIV- positive persons and is the first manifestation of AIDS in more than 50% of cases in developing countries. 5. In a developing country like India, the potential extra burden of new TB cases attributable to HIV could overwhelm budgets and support services, as has happened in countries most heavily affected by the HIV epidemic. WHO recommends people with TB/HIV complete their TB therapy prior to beginning anti-retroviral treatment unless there is a high risk of HIV disease progression and death during the period of TB treatment. In cases where a person needs TB and HIV treatment concurrently, first line treatment options include ZDV/ 3TC (lamivudine) or d4T(Stavudine)/3TC plus either an NNRTI or ABC (Abacavir). If an NNRTI-based regimen is used, EFZ (Efavirenz) would be the preferred drug as its potential to aggravate the hepatotoxicity of TB treatment appears less than with NVP (Nevirapine).

Antiretroviral Therapy for Individuals with Tuberculosis (WHO Recommendations- June 2002)

Situation Pulmonary TB and CD4 count < 50/ mm3 or extrapulmonary TB

Recommendations Start TB therapy. Start one of these regimens as soon as TB therapy is tolerated: ZDV/3TC/EFZ** ZDV/3TC/ABC ZDV/3TC/SQV/r ZDV/3TC/NVP* Start TB therapy. Start one of these regimens after 2 months of TB therapy: ZDV/3TC/EFZ** ZDV/3TC/ABC ZDV/3TC/SQV/r ZDV/3TC/NVP* Treat TB. Monitor CD4 counts if available. Start ART when indicated after ATT is completed.

Pulmonary TB and CD4 50-200/ mm3 or total lymphocyte count < 1200/mm3

Pulmonary TB and CD4 >200/mm3 or total lymphocyte count > 1200/mm3

*NVP is advised only in patients without other options because rifampicin reduces drug exposure to nevirapine by 31% and dose adjustments for NVP co-administered with rifampicin has not been established. **In HIV-infected pregnant women who have tuberculosis, efavirenz is contraindicated due to its teratogenicity.

(c) TREATMENT OF OPPORTUNISTIC INFECTION People with advanced HIV infection are vulnerable to infections and malignancies that are called 'opportunistic infections' because they take advantage of the opportunity offered by a weakened immune system. A partial list of the world's most common HIV-related opportunistic infections and diseases includes: 1. Bacterial diseases such as tuberculosis, MAC, bacterial pneumonia and septicaemia (blood poisoning) 2. Protozoal diseases such as PCP, toxoplasmosis, microsporidiosis, cryptosporidiosis, isopsoriasis and leishmaniasis 3. Fungal diseases such as candidiasis, cryptococcosis and penicilliosis 4. Viral diseases such as those caused by cytomegalovirus, herpes simplex and herpes zoster virus 5. HIV-associated malignancies such as Kaposi's sarcoma, lymphoma and squamous cell carcinoma. Low Cost AIDS Care : These activities would provide funding for home based and community based care, including increasing the availability of cost effective interventions for common opportunistic infections. Specific activity would include :1. establishing best practice guidelines and providing appropriate drugs for treating common opportunistic infections (OIs) at district hospitals. 2. training at selected State level hospitals for the provision of referral services. 3. improve the quality and cost effectiveness of interventions offered by existing procedures. 4. establish new support services for care for persons with AIDS in partnership with NGOs and CBOs by establishing small community based hospitals, hospice programmes, drop-incentres and home based care would be taken up. Necessary funds have been provided to all medical colleges and large hospitals in the country to ensure availability of drugs for management of opportunistic infections in HIV/AIDS patients. 60 Community care centers have been established in high prevalent States to provide palliative care to terminally ill AIDS patients. 39 Govt. medical college and referral hospitals have started free anti-retro-viral therapy

(d) PILOTING ART

ART(anti-retroviral treatment) is a new initiatives in this programme was launched on 1st April,2004 HAART regimen is used Combination of several (typically three or four) antiretroviral drugs is known as Highly Active Anti-Retroviral Therapy (HAART). Antiretroviral drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits. 1. Nucleoside & nucleotide reverse transcriptase inhibitors (NRTI) inhibit reverse transcription by being incorporated into the newly synthesized viral DNA and preventing its further elongation. 2. Non-nucleoside reverse transcriptase inhibitors (nNRTI) inhibit reserve transcriptase directly by binding to the enzyme and interfering with its function. 3. Protease inhibitors (PIs) target viral assembly by inhibiting the activity of protease, an enzyme used by HIV to cleave nascent proteins for final assembly of new virons. 4. Integrase inhibitors inhibit the enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial, and raltegravir became the first to receive FDA approval in October 2007. 5. Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. Maraviroc and enfuvirtide are the two currently available agents in this class. 6. Maturation inhibitors inhibit the last step in gag processing in which the viral capsid polyprotein is cleaved, thereby blocking the conversion of the polyprotein into the mature capsid protein . Because these viral particles have a defective core, the virions released consist mainly of non-infectious particles. There are no drugs in this class currently available, though two are under investigation, bevirimat and Vivecon. Antiretroviral drug treatment guidelines have changed many times. Early recommendations attempted a "hit hard, hit early" approach. A more conservative approach followed, with a starting point somewhere between 350 and 500 CD4+ T cells/mm. The current guidelines use new criteria to consider starting HAART, as described below. However, there remain a range of views on this subject and the decision of whether to commence treatment ultimately rests with the patient and their doctor.

The current guidelines for antiretroviral therapy (ART) from the World Health Organization reflect the 2003 changes to the guidelines and recommend that in resource-limited settings (that is, developing nations), HIV-infected adults and adolescents should start ART when HIV infection has been confirmed and one of the following conditions is present : 1. Clinically advanced HIV disease; 2. WHO Stage IV HIV disease, irrespective of the CD4 cell count; 3. WHO Stage III disease with consideration of using CD4 cell counts less than 350/l to assist decision making; 4. WHO Stage I or II HIV disease with CD4 cell counts less than 200/l.

The Govt of India provides ART at government hospital, free of cost for HIV cases in the six high prevalence states of Tamil Nadu, Andra Pradesh, Maharashtra, Karnataka, Manipur, Nagaland and in Delhi The priority categories are: 1. pregnant HIV women 2. children upto 15 years of age 3. full blown AIDS cases By Dec 2006,107 ART centers in 31 States and Union Territories are functional in India. About 56 000 patients are receiving free ART at the NGO and inter sectoral ART centers. A national ART monitoring and surveillance (M&E) system is established to provide accurate data and supervision. India has the capacity to scale up ART with advantages that many other countries do not have. These includes having an established domestic drug manufacturing base and enviable pool of trained health professionals.

(d) POST EXPOSURE PROPHYLAXIS Post exposure prophylaxis (PEP) refers to comprehensive medical management to minimise the risk of infection among Health Care Personnel (HCP) following potential exposure to blood-borne pathogens (HIV, HBV, HCV). This includes counselling, risk assessment, relevant laboratory investigations based on informed consent of the source and exposed person, first aid and depending on the risk assessment, the provision of short term (four weeks) of antiretroviral drugs, with follow up and support. Post HIV management is necessary to determine the status of exposure and the HIV status of the exposure source before starting (PEP) The decision to start PEP is based on the degree of exposure to HIV and the HIV status of the source from whom the exposure/infection has occurred The NACO guidelines are: Step 1: First aid in management of exposure For skin if the skin is broken after a needle-stick or sharp instrument: Immediately wash the wound and surrounding skin with water and soap, and rinse. Do not scrub. Do not use antiseptics or skin washes (bleach, chlorine, alcohol, betadine). After a splash of blood or body fluids on unbroken skin: Wash the area immediately Do not use antiseptics For the eye: Irrigate exposed eye immediately with water or normal saline. Sit in a chair, tilt head back and ask a colleague to gently pour water or normal saline over the eye. If wearing contact lens, leave them in place while irrigating, as they form a barrier over the eye and will help protect it. Once the eye is cleaned, remove the contact lens and clean them in the normal manner. This will make them safe to wear again Do not use soap or disinfectant on the eye. For mouth: Spit fluid out immediately Rinse the mouth thoroughly, using water or saline and spit again. Repeat this process several times Do not use soap or disinfectant in the mouth Consult the designated physician of the institution for management of the exposure immediately.

Step 2: Establish eligibility for PEP The HIV sero-conversion rate of 0.3% after an AEB (for percutaneous exposure) is an average rate. The risk of infection transmission is proportional to the amount of HIV transmitted, which depends on the nature of exposure and the status of the source patient. A baseline rapid HIV testing of exposed and source person must be done for PEP. However, initiation of PEP should not be delayed while waiting for the results of HIV testing of the source of exposure. Informed consent should be obtained before testing of the source as per national HIV testing guidelines. First PEP dose within 72 hours A designated person/trained doctor must assess the risk of HIV and HBV transmission following an AEB. This evaluation must be quick so as to start treatment without any delay, ideally within two hours but certainly within 72 hours; PEP is not effective when given more than 72 hours after exposure. The first dose of PEP should be administered within the first 72 hours of exposure. If the risk is insignificant, PEP could be discontinued, if already commenced. Assessing risk of transmission Exposure is defined under three categories based on the amount of blood/fluid involved and the entry port. These categories are intended to help in assessing the severity of the exposure but may not cover all possibilities. Categories of exposure Category Mild exposure Definition and example mucous membrane/non-intact skin with small volumes E.g.: a superficial wound (erosion of the epidermis) with a plain or low calibre needle, or contact with the eyes or mucous membranes, subcutaneous injections following small-bore needles. mucous membrane/non intact skin with large volumes OR percutaneous superficial exposure with solid needle E.g. : a cut or needle stick injury penetrating gloves percutaneous with large volume e.g.: an accident with a high calibre needle (>18 G) visibly contaminated with blood; a deep wound (haemorrhagic wound and/or very painful); transmission of a significant volume of blood; an accident with material that has previously been used intravenously or intra-arterially.

Moderate exposure Severe exposure

Assess exposed individual The exposed individual should have confidential counselling and assessment by an experienced physician. Exposed individuals who are known or discovered to be HIV positive should not receive PEP. They should be offered counselling and information on prevention of transmission and referred to clinical and laboratory assessment to

determine eligibility for antiretroviral therapy (ART). Besides the medical assessment, counselling exposed HCP is essential to allay fear and start PEP. Step 3: Counselling for PEP Exposed persons (clients) should receive appropriate information about what PEP is about and the risk and benefits of PEP in order to provide informed consent for taking PEP. It should be clear that PEP is not mandatory. Psychological support Many people feel anxious after exposure. Every exposed person needs to be informed about the risks, and the measures that can be taken. This will help to relieve part of the anxiety. Some clients may require further specialised psychological support. Document exposure Documentation of exposure is essential. Special leave from work should be considered initially for a period of two weeks. Subsequently, it can be extended based on the assessment of the exposed persons mental state, side effects and requirements. Practical application in the clinical settings For prophylactic treatment the exposed person must sign consent form. Informed consent also means that if the exposed person has been advised PEP, but refuses to start it, this needs to be recorded. This document should be kept by the designated officer for PEP. An information sheet covering the PEP and the biological follow-up after any AEB must be given to the person under treatment. However, this sheet cannot replace verbal explanations. Step 4: Prescribe PEP Deciding on PEP regimen There are two types of regimens: Basic regimen: 2-drug combination Expanded regimen: 3-drug combination The decision to initiate the type of regimen depends on the type of exposure and HIV serostatus of the source person. HIV PEP Evaluation Exposure Status of Source HIV+ and Clinically symptomatic Mild Consider 2-drug Start 2- drug PEP PEP Moderate Start 2-drug Start 3- drug PEP PEP Severe Start 3-drug Start 3- drug PEP PEP HIV+ and Asymptomatic HIV status unknown Usually no PEP or consider 2-drug PEP Usually no PEP or consider 2-drug PEP Usually no PEP or consider 2-drug PEP

In the case of a high risk exposure from a source patient who has been exposed to or is taking antiretroviral medications, consult an expert to choose the PEP regimen, as the risk of drug resistance is high. Refer/consult expert physician. Start 2-drug regimen first.

Step 5: HIV chemoprophylaxis Because post-exposure prophylaxis (PEP) has its greatest effect if begun within two hours of exposure, it is essential to act immediately. The prophylaxis needs to be continued for four weeks. Exposure must be immediately reported to designated authority and therapy administered. Never delay start of therapy due to debate over regimen. Begin with basic 2-drug regimen, and once expert advice is obtained, change as required.

Dosage of drugs for PEP Medication Zidovudine (AZT) Stavudine (d4T) Lamivudine (3TC) Protease Inhibitors 2-drug regimen 300 mg twice a day 30 mg twice a day 150 mg twice a day 3-drug regimen 300 mg twice a day 30 mg twice a day 150 mg twice a day 1st choice Lopinavir/ritonavir (LPV/r) 400/100 mg twice a day or 800/200 mg once daily with meals 2nd choice Nelfinavir (NLF) 1250 mg twice a day or 750 mg three times a day with empty stomach 3rd choice Indinavir (IND) 800 mg every 8 hours and drink 810 glasses (1.5 litres) of water daily

Note: If protease inhibitor is not available and the 3rd drug is indicated, one can consider using Efavirenz (EFV 600 mg once daily). Monitoring should be instituted for side effects of this drug eg CNS toxicity such as nightmares, insomnia etc. * Fixed Dose Combination (FDC) are preferred, if available. Ritonavir requires refrigeration.

PEP regimens to be prescribed by Health Centres Preferred Alternative 2-drug regimen Zidovudine (AZT) + Stavudine (d4T) + Lamivudine (basic PEP regimen) Lamivudine (3TC) (3TC) 3-drug regimen (consult expert opinion for starting 3 drug eg LPV/r, NLF or IND regimen) Not recommended ddI + d4T combination NNRTI such as Nevirapine should not be used in PEP Selection of PEP regimen when the source patient is on ART The physician should consider the comparative risk represented by the exposure taking in view exposure sources history of and response to antiretroviral therapy based on clinical response, CD4 cell counts, viral load measurements (if available), and current disease stage (WHO clinical staging and history). If the source persons virus is known or suspected to be resistant to one or more drugs considered for the PEP regimen, exposed person needs to be given alternate PEP drug regimen, and referred for expert opinion. Changes in the PEP regimen can be made after PEP has been started. Re-evaluation of the exposed person should be considered within 72 hours post-exposure, especially as additional information about the exposure or source person becomes available.

ARV drugs during pregnancy Data regarding the potential effects of antiretroviral drugs on the developing foetus or neonate are limited. There is a clear contraindication for Efavirenz (first 3 months of pregnancy) and Indinavir (pre natal). For a female HCP considering PEP, a pregnancy test is recommended in case of a doubt. Pregnant HCP are recommended to begin the basic 2-drug regimen, and if a third drug is needed, Nelfinavir is the drug of choice. Step 6: Follow-up of an exposed person Whether or not post-exposure prophylaxis is started, a follow up is needed to monitor for possible infections and to provide psychological support. Clinical follow-up In the weeks following an AEB, the exposed person must be monitored for the eventual appearance of signs indicating an HIV seroconversion: acute fever, generalized lymphadenopathy, cutaneous eruption, pharyngitis, non-specific flu symptoms and ulcers of the mouth or genital area. These symptoms appear in 50%-70% of individuals with an HIV primary (acute) infection and almost always within 3 to 6 weeks after exposure. When a primary (acute) infection is suspected, referral to an ART centre or for expert opinion should be arranged rapidly.

An exposed person should be advised to use precautions (e.g., avoid blood or tissue donations, breastfeeding, unprotected sexual relations or pregnancy) to prevent secondary transmission, especially during the first 612 weeks following exposure. Condom use is essential. Drug adherence and side effect counselling should be provided and reinforced at every follow-up visit. Psychological support and mental health counselling is often required. Laboratory follow-up Exposed persons should have post-PEP HIV tests. HIV-test at 3 months and again at 6 months is recommended. If the test at 6 months is negative, no further testing is recommended.