Presentación de datos

Antiretroviral Therapy was first introduced in 1990 and since then has continued to be used by HIV-positive patients worldwide(Shetty, 2008). It helped in reducing mortality in many hospital and treatment centres by improving patients survival rate (Mukherjee, Ivers, Leandre, Farmer, & Behforouz, 2006). In many developing countries, the provision of ART also require patients to be well-educated about the disease, associated opportunistic infections and the need for constant adherence to treatment (C. E. Golin et al., 2002). Patients who have been prescribed ART need to take it for the rest of their lives. The ART if used properly can control and reduce the virus level in HIV patients (J. B. Nachega et al., 2007).

Antiretroviral treatments help in rebuilding the immune system, preventing the virus from multiplying and increasing the duration of a patient’s life(Soares & Costa, 2011).

The biggest challenges facing the use of antiretroviral in poor countries include poor healthcare infrastructure, high cost of second line treatment and the developing of drug resistance (Gilks et al., 2006; Richard et al., 2004). There are also concerns pertaining to the non-adherence to treatment which will result in failure of treatment and accumulation of strains of highly resistant virus that can promote the spread of drug resistance.

The current treatment of ART is in a combination form known as the Highly Active Antiretroviral Therapy (HAART) (Severe et al., 2005). Three classes of HAART are used in most parts of the world. These include protease inhibitors, non‐nucleoside reverse transcriptase inhibitors (NNR‐TIs) and nucleoside reverse transcriptase inhibitors (NRTIs). All HAART classes have adverse effects which have severe impact on its usage and on patients’ adherence to treatment (Dybul, Fauci, Bartlett, Kaplan, &

Pau, 2002). First-line treatments are cheap and easy to use compared to second-line treatments which are very expensive and need to be used only when the first line of treatment fails (Urquhart, 1995).

Some of the significant achievements attributed to HAART are reduction in HIV/AIDS-related mortalities, keeping HIV-positive patients at their homes, helping them to continue with their jobs and emptying hospital wards of HIV/AIDS patients (Akileswaran et al., 2005). The high cost of HAART in many developing countries has made it unavailable to poor patients and necessitated the interventions of WHO and other international organizations to provide the medication (De Cock & De Lay, 2008).

The benefits of HAART are great despite its high cost, as it is one of the most useful medication in the fight against infectious diseases in the twenty first century. It is estimated that more than 790,000 deaths would be avoided if the coverage is up to 50%, while the 100% coverage model could avert up to 1,900,000 deaths over the same period (Guimarães et al., 2008).

2.3.1 Type and combination of antiretroviral drugs

HAART combination was developed for the first time in 1996 for the treatment of HIV/AIDS(Cooper et al., 2002). Since that date the combination has contributed significantly in reducing mortality and morbidity among HIV positive patients. The medications have also contributed in emptying hospital words from HIV positive patients. Antiretroviral therapy had the primary aims of improving duration and quality of life, reducing HIV transmission, as well as reducing HIV-related illnesses and deaths.

Antiretroviral treatment also has the benefit of reducing the risk of Mother-to-Child HIV Transmission (MTCT) rate when used accurately and at the requested time for the benift of both mother and child (Bogart et al., 2006).

Even though HAART has contributed significantly in fighting against the disease, eradication of the virus is impossible due to the fact that CD4 cells get infected during the acute HIV stage and continues on (Ledergerber, 2004). The goal of maximal viral suppression at the beginning of treatment in some cases may be very difficult due to the resistance strains of the virus. A successful HAART must combine at least two to three drugs from at least 2 different classes of treatment (Carpenter et al., 2000; Struble et al., 2005). Changing from the first line to the second line of treatment may be due to failure of the first line of treatment (Gulick, 2003; Marks & Gulick, 2004).

The most common combination of antiretroviral regimens for treatment in HIV patients generally consists of one NNRTI with two NRTIs or a PI (with or without ritonavir-boosting) with two NR. The antiretroviral treatment (ART) combination of Efavirenz, Stavudine, Lamivudine and Nevirapine is the most frequently used initial regimen in many developing countries including Malaysia. In Malaysia, first-line HAART are provided at no charge by the Ministry Of Health to all patients. Malaysia spends more than USD 3.5 million on HIV/AIDS treatment since the majority of patients are drug users and cannot afford to pay for their medication (Sluis-Cremer & Tachedjian, 2008).

2.3.2 Starting Antiretroviral Therapy

Patients who suffer from an AIDS-defining disease and those whose CD4 cell counts below 200 cells/mm are classified at WHO stage 4 irrespective of their CD4+ cell count. Furthermore, the psychosocial considerations of the patient should be considered before patients are offered ART (Gilks et al., 2006). HIV-positive patients whose CD4 counts are very low and whose clinical status showed progression towards AIDS require immediate start of HAART. In general, the decision to start HAART should be made for the benefit of the patients. Secondary aims of starting antiretroviral treatment include

relieving patients’ symptoms, rebuilding and improving the immune system and partial reduction of viral load (Bradley-Springer et al., 2002; Nackchuay, 2009). One of the problems associated with starting or changing antiretroviral treatment is the development of toxicities or side effects to such treatment.

2.3.3 Side effects of antiretroviral drugs

Current HIV treatments need to be administered conteniously to suppress viral replication. HAART, like most other medication, comes with negative aspects such as unwanted drug interactions, drug toxicity, heavy pill burden, pill fatigue and side effects (Rudorf & Krikorian, 2005). Development of resistance to HAART has emerged in all countries worldwide(Mocroft et al., 2001). These toxicities affect most patients undergoing treatment and may result in non-adherence. Complications of HAART include diabetes, renal failure, abnormal blood lipids and liver damage. Other common adverse effects of antiretroviral treatment are vomiting, fever, skin rashes, headache, weight loss and diarrhoea (Bates, 1996). These side-effects of HAART can be classified as acute and long-term, and from mild to severe reactions(Borras-Blasco, Navarro-Ruiz, Borras, & Castera, 2008). This is due to the variability of absorption, distribution and elimination of drugs from patient to patient(Kiertiburanakul & Sungkanuparph, 2009).

Side effects of treatment depend on the type and class of the medication used. NRTIs are commonly used in most countries including Malaysia and they are known to be associated with bone-marrow suppression with subsequent anaemia, peripheral neuropathy, pancreatitis and mitochondrial toxicity, manifesting as myopathy (weakening of the muscles)(Mkhize, 2007). These drugs include d4T, AZT and 3TC (Hofstede, De Marie, Foudraine, Danner, & Brinkman, 2000; Lee, Hanes, & Johnson, 2003). In HAART group, Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) is

the most commonly used group in Malaysia(Lapadula et al., 2008). Efavirenz is the most common drug used by HIV-positive patients in Malaysia and it is known to be associated mostly with adverse effects such as drowsiness, depression and anxiety, which usually results in the patient’s refusal of treatment(O'Connor et al., 2007).

The NRTI may cause hepatic toxicity and nevirapine, in particular, is known for its association with skin rash and systemic hypersensitivity (Clarke et al., 2001; De Clercq, 2004). Protease Inhibitors (PI) are known to be very costly and not provided for free in most developing countries including Malaysia and are associated with many side effects (d’Almeida et al., 2008). One of the most common side effects is hyperurisaemia leading to gout, increased risk of cardiovascular events like heart failure, anaemia and elevated liver enzymes (Carr et al., 1998; Riddle, Kuhel, Woollett, Fichtenbaum, & Hui, 2001). Almost all known medications are associated with adverse effects including the new generation of antiretroviral therapy and these could be the main causes of drug resistance and treatment failure (Siripassorn et al., ; Wainberg, Martinez-Cajas, &

Brenner, 2007).

2.3.4 Antiretroviral drug resistance

Resistance to treatment in general is a well-established biological process occurring with infectious agents such as viruses, parasites and bacteria (Laing, 2005; Stokes, 2002). In Malaysia, the issue of resistance to HAART is not well studied and there are no published articles on this vital issue. This study will serve as a foundation since we are looking into adherence and also examining the common type of adverse effects to treatment. Resistance to medication in the HIV situation is mostly affected by the very fast replication of the virus and the fact that the virus can easily become inactive and does not respond to HAART (Fumero & Podzamczer, 2003). Adherence to HAART is

highly needed at the commencement of therapy due to high viral load. Non-adherence at the beginning of therapy is more highly associated with development of drug resistance than after six months of therapy due to the fact that the viral load would have been low at this time (Glass et al., 2006; Vlahov & Celentano, 2006).