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Compiled by Linda-Gail Bekker
Dr Bekker is a regular contributor to HIV/AIDS UPDATE. Dr Bekker was born in Zimbabwe and completed her medical training at the University of Cape Town (UCT) in South Africa. She spent four years in KwaZulu Natal working in infectious diseases, paediatrics and medicine, amongst others. Dr Bekker qualified as a physician at UCT (Groot Schuur Hospital) in 1996. She is currently completing her PhD in HIV/TB immunology as a Fogharty Fellow at Rockefeller and Columbia University in New York City.
T-20 - the next big gun?
The hot new antiretroviral drug of the moment is T-20 (Pentafuside), a fusion inhibitor that offers a glimpse of the next frontier of anti-HIV therapy. T-20 is a leading member of a new class of drugs. It blocks HIV entry into cells by interfering with gp41, a protein on the outside surface of HIV that is part of the molecular key used to open cell doorways.
The excitement began in November 1998, when Nature Medicine published impressive results from a two-week test of the drug. Researchers at the University of Alabama at Birmingham studied the effect of the drug in 16 trial participants. Four out of four participants receiving the highest dose (2 x 100 mg doses per day) had a drop in viral load to below 500 copies within 10-14 days.
Based on this, T-20 seems as effective as the most potent protease inhibitor on the market. This is good news for people on failing regimens since T-20 has a different target to existing drugs and can be used where drugs have failed due to resistance. Cost, however, will be a factor since T-20 is manufactured from scratch, which is an expensive process.
Immune restoration disease
It has been noted that there are some negative clinical effects of immune reconstitution. Along with the possibility that HAART may restore pathogen-specific immune responses - including delayed tissue hypersensitivity and lymphocyte proliferation - comes the threat that such responses against a subclinical or residual infection may cause tissue inflammation resulting in immune restoration disease.
In a recent report published in the Lancet, Dr. Anthony Japour and colleagues described the experiences of five patients with advanced HIV-1 disease (all with baseline CD4+ counts <50/mm3) who developed fever, leukocytosis, and lymphadenopathy within 1-3 weeks after addition of adefovir to an antiretroviral regimen.
All five patients were found to have increases in CD4+ counts ranging from 2-19 fold after starting indinavir. Microbacterial avium complex infection was diagnosed in lymph node specimens and granulomatous responses and acid fast bacilli were seen on histology.
It seems that partial immune reconstitution after initiation of HAART in these points resulted in intense inflammatory response to MAC infection, resulting in MAC lymphadenitis, an uncommon syndrome in HIV.
Similar problems have been seen with CMV with an increase in macular edema, retinal membranes and uveitis in points starting HAART and presumably undergoing partial immune reconstitution and inflammation.
PCP prophylaxis: In a trial for TMP/ SMX (Bactrim) sensitive patients done in New York, Dapsone (100 mg) daily was found to be of equivalent benefit to Atavaquone(1 500 mg) daily. Adverse event rate was found to be similar in both drugs, though Atavaquone tends to cause nausea and diarrhoea, whereas Dapsone tends to cause hypersensitvity and anaemia. El-Sadr WM, NEJM, Dec 24, 1998.
Fungal Infection and prophylaxis: Researchers compared fluconazole 400 mg weekly with fluconazole 200 mg daily. The two regimes were found to be roughly equivalent in preventing invasive fungal disease. However, the weekly regime was slightly less efficacious than the daily regime in preventing thrush.. This, and other studies, confirm the routine use of fluconazole in the primary prevention of fungal disease is not warranted. Hvlir et al., Clin Inf Dis, Dec 1998.
The Center for Disease Control and Ivory Coast Ministry of Public Health reported at the 12th World AIDS Conference that HIV infected African patients who were co-infected with tuberculosis had a 48% decline in mortality and a 44% drop in hospitalizations after receiving trimethprim/ sulfamethoxazole.
Patients in Africa who are co-infected with TB and HIV have a high mortality rate, often dying due to other diseases such as toxoplasmosis, pneumococcal pneumonia and salmonellosis. In the trial, TMP/SMX treatment was initiated one month after TB treatment.
According to the researchers, the drug was safe and effective in preventing these diseases. The researchers feel that the drugs will have a significant effect on the mortality rate and quality of life of HV infected TB patients in developing nations.
Recommendation: commence primary prophylaxis against PCP (pneumocystis carinii pneumonia) and the other infections mentioned here with cotrimoxazole (TMP/SMX) at 480mg daily (single strength tablet). This should occur once the CD4 count is below 200, the lymphocyte count is less than 1 250 or HIV disease becomes symptomatic (Stage III).
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