Antiretroviral Therapy  (ART)

(Source WHO)

INTRODUCTION

The Acquired Immunodeficiency Syndrome (AIDS) was first reported in the Morbidity and Mortality Weekly Report as “Pneumocystis pneumonia – Los Angeles,” in 1981. Since then, AIDS has become the most devastating disease that mankind has ever faced.

Since the epidemic began, more than 60 million people have been infected with the human immunodeficiency virus (HIV). By the end of 2001 an estimated 40 million people globally were living with HIV with about one-third aged between 15-24 years. Ninety-five percent of new infections are occurring in developing countries and almost 50% are women.

HIV/AIDS was late in coming to Asia. Until the late 1980s, no country in the region had experienced a major epidemic and, in 1999, only Cambodia, Myanmar and Thailand had documented significant nationwide epidemics. This situation is now rapidly changing. In 2001, 1.07 million adults and children were newly infected with HIV in Asia and the Pacific bringing to total of 7.1 million people living with HIV/AIDS in this region. Of particular concern are the marked increases registered in some of the world’s most heavily populated countries. At the end of 2001, the national adult HIV prevalence rate in India was under 1%, with an estimated 3.97 million Indians living with HIV/AIDS. India ranks second after South Africa in the number of people living with HIV/AIDS. In Indonesia and Nepal there are concentrated epidemics in high-risk groups such as injecting drug users (IDU). In Bangladesh, Bhutan, Maldives and Sri Lanka infection rates are low, though risk behaviour is common. TB is the leading opportunistic infection in HIV-positive persons. HIV fuels the TB epidemic and is a particular threat to Asia and the Pacific, which bears more than 60% of the World’s TB burden.

Early, large-scale and focused prevention programmes can reduce infection rates in high-risk groups and the risk of spread of HIV among the wider population. An excellent example is Thailand, where prevention efforts have probably averted millions of HIV infections. Cambodia is another example where preventive measures have been effective. Strategies to prevent HIV transmission should remain a priority in combating HIV/AIDS.

ANTIRETROVIRAL TREATMENT (ART)

Antiretroviral Treatment for HIV infected patients was first introduced in 1986. Zidovudine (ZDV), a nucleoside reverse transcriptase inhibitor (NsRTI), was the first drug that was used and was shown to reduce deaths and accompanying opportunistic infections in patients with advanced HIV infection. Over the next few years other NsRTIs like didanosine (ddl), lamivudine (3TC), and stavudine (d4T) were introduced. However, the benefits of single drug therapy were short-lived due to the emergence of resistance. Subsequently, it was shown that combining 2 or 3 antiretroviral (ARV) drugs produced more sustained benefit. New classes of drugs, the protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) permitted the use of more potent antiretroviral regimens. These regimens, consisting of three or more drugs, have resulted in dramatic reduction in HIV levels in blood and markedly improved immune function. In developed countries treatment of HIV infection using regimens of 3 or more antiretroviral drugs has been recommended.

In Europe and North America, AIDS mortality has dropped significantly in large part due to access to regimens of 3 or more antiretroviral drugs. Patients receiving these regimens are less likely to develop opportunistic infections including TB and require less admission to hospital than patients with untreated infection. Combination antiretroviral therapy (ART) leads to reduction in plasma HIV RNA level (viral load) and rise in CD4 counts with at least partial restoration of immune function. Combination therapy also significantly slows the progression of HIV infection. Furthermore, studies indicate that low viral load is associated with lower risk of heterosexual and perinatal transmission. Although combination of three antiretroviral drugs is expensive, studies indicate that it is a cost effective use of resources in the developed world. Since the advent of combination antiretroviral therapy, the infection has been transformed into a treatable and chronic condition for a significant proportion of those with access to this treatment. Appropriate treatment can prevent not only infected individuals from succumbing to life-threatening illness   but plays a major role in prevention by reducing viral load of those under treatment.

Possible nucleoside reverse transcriptase inhibitor (NsRTI … ART)   ) combinations include:

Zidovudine + lamivudine

Stavudine + lamivudine

Zidovudine + didanosine

Didanosine + lamivudine

Stavudine + didanosine

Zidovudine and stavudine are not used together due to their antagonistic effects.

Zidovudine + lamivudine + abacavir may be combined as 3 NsRTI regimen.

The dual combination of stavudine + didanosine should only be used during pregnancy when no other alternatives exist.

ART is a life long therapy and adherence to ART regimen is of the utmost importance. The Treatment MUST be taken on time everyday, twice a day or as recommended by the doctor. Non adherence will lead to ‘drug resistance’ which is a dangerous and critical state of health. ART reduces the incidence of Opportunistic Infections thereby keeping the person healthy and improves the quality of life. People on ART can work, play and lead a normal life.

The Government of India provides  FREE ARV to patients who require it. ARV is dispensed from an ART Centre, usually located in a government hospital. If located in a private hospital the ART Centre is monitored by the government.

The nine ART Centres in Delhi are all located in government hospitals. The hospitals are:

Guru Teg Bahadur,  LNJP, RML, AIIMs,  Safdarjung,  Deen Dayal,  Ambedkar, Kalawati and Chacha Nehru Hospital for Children.

 MONITORING.

Clinical monitoring includes a monthly follow up visit to the ART Centre dispensing ARV where the patient is checked for any physical changes in body condition, reactions to treatment, progression of disease.

Monitoring indicators showing a positive response to therapy include: Increase in body weight and decrease in frequency and intensity of Opportunistic Infections.

Laboratory Investigations are necessary to monitor drug adverse effects, appearance of new disease or progression of disease. These may include CBC(Complete Blood Count).Serum Alt or Ast, Serum Creatinine, blood glucose, serum lipids but in a Resource Limited Setting monitoring of infection progression and response to treatment will be assesed by clinical indicators and CD4 cell count.

 ADHERENCE.

A 90 to 95% of adherence is necessary for optimal virological suppression. Maintaining this level of adherence is difficult but lesser degrees of adherence are more often associated with virological failure.

Adherence may be measured by patient self report, pill count and report of primary care giver:

Number of doses missed in the last seven days.

Number of doses missed since last visit to ART Centre..

If dose taken at the correct time, if not ask for delay in hours/days.

Specific reason for  interruption or modification/failure to take prescribed dose.

Factors associated with poor adherence are poor patient clinician relationship, high pill burden, forgetfulness, mental depression, lack of patient education, inability of patients to identify their medication, drug toxicity and being too ill.

 PRIOR TO STARTING ART

Prior to starting ART the patient’s ‘willingness’ to take such therapy should be clearly established. A treatment plan made, shared, understood and committed to by the patient. The importance of taking the medication as prescribed, at the correct time understood and the implications of non compliance understood by the patient. Written instructions should be given to help patient understand the use of the prescribed drugs. Possible side effects must be explained in advance. Educate the patient’s family and friends is very helpful. A patient suffering from drug abuse or mental illness may benefit more if these problems are discussed in advance and taken care of before starting ARV.A Trusting and caring relationship between patient and health care provider is essential. The health care team should have updated information on ARV and Adherence and should undertake training if necessary. New Medical problems may influence adherence and in some such cases it may be appropriate to discontinue all medication than uncertain adherence BUT this should be decided by the treating doctor.

CHANGING THERAPY

The reason to change ARV therapy include Drug resistance, adverse effects/intolerance, treatment failure, active TB and pregnancy.

 WOMEN and PREGNANCY

ART recommendations for HIV infected pregnant women are based upon the principle that therapies of known benefit to women should not be withheld during pregnancy unless the risk of adverse effects on the mother, foetus or infant outweighs the expected benefit to the woman. Pregnancy or the desire to become pregnant should not preclude the use of optimal ART but pregnancy may affect the ‘choice’ of ART.

For Pregnant women who are infected BUT are not on ART the use of ART drugs to reduce the risk of transmission  from mother to child is recommended.

For pregnant women already on ART the options are to temporarily discontinue ART during early stages of pregnancy (First trimester), to continue with same therapy or change to a different regimen. A Change in ART should be considered if  the drug being received is severely toxic causing gastrointestinal intolerance compounded by  morning sickness, in such cases all drugs should be stopped and re started simultaneously.

Breast Feeding HIV Infected women should be fully  informed of  the risks and benefits of  breast feeding.

Ideally an infected woman should avoid breast feeding to reduce the risk of mother to child transmission. However, in resource limited settings Exclusive breast feeding for the first six months is recommended and she should continue with her ART.

In Non pregnant women the recommendations to start ART are similar for men and women.

ADOLESCENTS.

Adolescents, more than 13 years of age, infected with HIV through the sexual or injecting drug route have an ART regimen similar to adults based on body weight. Children infected through parent (vertical transmission) or through blood products/injections in a clinical setting should receive ART based on pediatric guidelines.

 TUBERCULOSIS

Due to a high prevalence of TB in the South East Asia region. A TB co infection with HIV is most common, in such cases (HIV and TB), TB treatment following DOTs strategy should be initiated promptly but management of this co infection is complicated. If  patients already on ART develop TB they should adjust the regimen to be compatible with a TB treatment.. Following completion of anti tubercular therapy, the ART regimen can be continued or changed depending on the clinical and immunologic status of the patient.

 CONCLUSION

The impact of the ART programme depends on the availability and utilization of ICTCs (Integrated Counselling and Testing Centres),  availability of trained Health Care workers, laboratory capacity, availability of ART 1st line and 2nd line regimens and funds to sustain the programme.