Chapter 10 Human Immuno Deficiency Virus Infection

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1 143 Chapter 10 Human Immuno Deficiency Virus Infection Chapter 10 Human Immuno Deficiency Virus Infection HIV infection Clinical Features Clinical Staging of HIV infection recommended by WHO Diagnosis Treatment Indicators for starting antiretroviral treatment Figure 10.1 Global picture of HIV infection Figure 10.2 The HIV virus Figure 10.3 Replication of HIV (schematic) Figure 10.4 HIV particles budding from infected cell

2 144 HIV infection In 2005 there were 40 million people living with HIV infection. In the same year there were about 5 million new infections reported, and there were 3 million deaths. These statistics are indicative of the seriousness of the disease. Figure 10.1 Global picture of HIV infection HIV is an RNA virus that only infects cells with a particular marker known as CD4. This marker is found on T-lymphocyte helper cells. It is also found on macrophages and other cells like dendritic cells and microglial cells which form a reservoir of chronically infected cells. Figure 10.2 The HIV virus 144

3 145 Figure 10.3 Replication of HIV (schematic) Figure 10.4 HIV particles budding from infected cell 145

4 146 In a normal adult CD4 cells in the peripheral blood number /ml. The number declines during HIV infection and this provides a good indicator of clinical features. CD4 count cells/ml Implication >500 Normal Minor opportunistic infections <350 Indicator for treatment <200 Risk of major opportunistic infections <50 Potentially fatal complications The possibility of HIV infection should be considered in any individual who has been referred to several hospital specialties without a diagnosis that could account for the illness, and particularly if there is lymphopenia and/or thrombocytopenia. Clinical Features Most children who become infected acquire the virus from the mother. Mother-to-child transmission rates vary from 13% to 42%. Transmission rate is twice as high in Africa as in Europe (25 to 35% compared to 15 to 20%). Transmission rates are higher in pre-term infants, first born twin, and if the mother has advanced HIV disease with high plasma HIV concentration of RNA and low CD4 count, and duration of rupture of membranes. Postnatal transmission through breast milk is about 14 per cent over and above transmission in utero or at delivery, less so in exclusively breast fed infants. The future impact of paediatric HIV infection will be directly related to the incidence of infection amongst women. Two-thirds of mother-to-child transmission occurs in the period around birth, the peripartum period. It could happen in utero (around a third of cases), mostly late in the third trimester, or intra-partum period (around two-thirds of cases). Mother-to-child transmission also arises after birth during breast feeding as mentioned above. In children patterns of disease expression and progression differ. Recurrent bacterial infections like pneumonia, meningitis, urinary infections should arouse suspicion. Check should be made for generalized enlargement of lymph glands, liver and spleen. In addition oral thrush and parotitis, if present, call for full investigation or referral. A positive HIV test in a child invariably means that the mother and possibly the father are also infected. Most children with HIV acquired from the mother display features of HIV infection within 6 months of life Age of onset of any sign of HIV-1 infection predicts length of survival. About a quarter (23-26%) have a rapidly downhill course and develop features characteristic of AIDS within the first year of life. These infants are more likely to have been born to mothers with advanced disease or to have been infected in utero compared to those whose disease progresses slowly. Others develop AIDS slowly over several years; those who acquired HIV as vertical transmission from the mother will usually display features of HIV infection within 6 months of life. 146

5 147 About 30-50% children present with an early onset of opportunistic infection. Pneumocystis carinii pneumonia is commoner in children than in adults with a peak incidence between age 3 to 6 months. Other opportunistic infections are toxoplasmosis, tuberculosis, cryptosporidiosis, and candida infections. Serious bacterial infections, particularly pneumonia and urinary tract infections are also common. Progressive encephalopathy has been reported as the first manifestation in about 10-15% of children. Single organ disease such as cardiomyopathy, nephropathy, unexplained cognitive or growth failure, and cancers (e.g. lymphoma; Kaposi s sarcoma) may present as the first clinical problem in previously well school age children. Growth faltering is a problem in symptomatic children. Any infection is associated with episodes of weight loss. Fig A Pneumocystis carinii pneumonia Fig B Shrunken cerebral hemispheres in HIV Fig C Malignant lymphoma of post auricular gland 147

6 148 Clinical Staging of HIV infection recommended by WHO Stage 1 Asymptomatic Persistent generalized lymphadenopathy Stage2 Hepatosplenomegaly Fungal infection of nails Parotid enlargement Recurrent or chronic upper respiratory tract infection Stage 3 Unexplained malnutrition not responding to treatment Unexplained persistent diarrhoea Unexplained persistent fever Oral thrush Pulmonary tuberculosis Severe recurrent bacterial pneumonia Unexplained anaemia (Hb <8gm/dl), or neutropenia (<500/mm 3 ), or thrombocytopenia (< 30,000/mm 3 ) for >1 month Stage 4 Unexplained severe wasting or severe malnutrition Pneumocystis pneumonia Recurrent severe bacterial infections Disseminated tuberculosis Cryptosporidiosis Kaposi s sarcoma B-cell non-hodgkin lymphoma HIV encephalopathy, or cardiopathy, or nephropathy. Diagnosis Maternal antibodies tend to persist for as long as 18 months. Hence conventional antibody tests do not help. Virus culture and polymerase chain reaction (PCR) are most reliable in the first 2 months and are sensitive, but may not be easily available. p24 antigen test in the newborn serum is less sensitive than virus culture but can achieve similar results by age 6 months. Treatment Without treatment HIV infected children in developing countries suffer a mortality rate of 45-59% by 2 years of age. Antiretroviral therapy is now becoming more widely available. There are three main groups of drugs viz. nucleoside analogue reverse transcriptase inhibitors; 148

7 149 non-nucleoside reverse transcriptase inhibitors protease inhibitors. Current recommendations are to commence treatment with 2 nucleoside reverse transcriptase inhibitors plus one non-nucleoside reverse transcriptase inhibitor. Protease inhibitors are recommended for second line therapy in resource poor settings because of their costs. The drugs and their doses are listed in the table below: Drug Nucleoside analogue reverse transcriptase inhibitors Zidovudine Lamivudine Stavudine Didanosine Abacavir Dose 4 mg/kg twice per day 4 mg/kg twice per day (maximum 150 mg per dose) 1 mg/kg twice per day Infants <3 months 50 mg/m 2 twice per day; children >3 months 120 mg/m 2 twice per day 8 mg/kg twice per day only for children > 3 months old. Non-nucleoside reverse transcriptase inhibitors Nevirapine Efavirenz mg/m 2 twice per day (maximum 200 mg per dose) 15 mg/kg once per day Protease inhibitors Nelfinavir Lopinavir/ritonavir Saquinavir Children over 2 years mg/kg twice per day (maximum of 2 g per dose Child 7-15 kg: 12 mg/kg lopinavir; 3 mg/kg ritonavir Child 15-40kg: 10 mg/kg lopinavir; 2.5 mg/kg ritonavir 50 mg/kg three times per day 149

8 150 A difficulty with treating HIV infection, besides the cost of the drugs, is that the virus mutates rapidly and after a time becomes resistant to one or more of the drugs in the regimen. Hence first line and second line regimens have been recommended. First line regimen Stavudine or Zidovudine (NRTI) Plus Lamivudine (NRTI) Plus Nevirapine or Elavirenz (NNRTI) Second line regimen Abacavir (NRTI) Plus Didanosine (NRTI) Plus Protease inhibitor Lopinavir/ritonavir or Nelfinavir or Saquinavir When to commence treatment is decided by the stage of the illness, and this decision is best carried out at a specialist clinic. Different countries have established their own guidelines based on the availability of drugs. The following recommendations for starting treatment take into account several national guidelines: Indicators for starting antiretroviral treatment Recurrent HIV related hospital admissions > 2 admissions per year Prolonged > 4 weeks HIV related hospital admission CD4+ cells < 15% in children over the age of 18 months CD4+ cells < 20% in children less than 18 months old Stage 2 or 3 disease in all age groups. 150

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