Management of HIV Infected Individual
Drugs that are presently available for anti-retroviral therapy are classified into five categories.
- Nucleoside analogues that include zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir and adefovir dipivoxil;
- Non-nucleoside reverse transcriptase inhibitors that include nevirapine, delvirdine and efavirenz;
- protease inhibitors that include saquinavir, indinavir, ritonavir and nelfinavir;
- Nucleotide reverse transcriptase inhibitors that include adefovir;
- and ribonuleotide reductase inhibitors that include hydroxyurea.
Current recommendations for starting anti-retroviral therapy indicate that individuals with acute HIV infection if seen within 6 months after seroconversion and patients having symptoms consistent with AIDS should receive therapy regardless of the CD4 count or HIV RNA load. If the individual is asymptomatic and CD4 count is less than 500/mm3 or HIV RNA levels are more than 20,000 by RT-PCR technique then treatment should be offered. If the individual is asymptomatic and CD4 count is more than 500/mm3 or HIV RNA levels are less than 20,000 by RT-PCR technique then treatment would be delayed by most experts and the patient would be observed in most instances.
These recommendations are based on strong evidence of clinical and virological benefit seen in various studies. A three-drug combination is recommended and one may chose two from the nucleoside analogues and one from the protease inhibitors. Depending on the pretreatment viral load virologic response, as assessed by viral RNA studies may take up to six months.
If therapy is not effective then it needs to be changed. The following are the indications:
- Treatment failure as suggested by a confirmed rising plasma HIV RNA level or a failure to achieve the desired reduction, declining CD4 counts and clinical disease progression.
- Unacceptable toxicity of, intolerance to, or non-adherence to the regimen.
- Current use of suboptimal regimens. The alternatives depend on the reasons for discontinuing therapy in the first place. This means that drugs given earlier should not be given again.
There are several problems with therapy. The optimum duration is not known. The regimens are complex and may involve intake of more than 20 tablets per day. The cost of currently available drugs in the three-drug regimen is more than Rs 20,000/- per month plus that of laboratory tests. Each viral load estimation costs more than Rs 10,000/-. Unless the patient is highly motivated and has all the resources to buy these drugs for a prolonged period of time it would be inadvisable to start therapy, as inadequate or suboptimal therapy would only result in drug resistance. Finally, in spite of all the costs involved no one can guarantee a cure. At best this uniformly fatal disease can be turned into a chronic disorder.
At our Institute, we have been trying out an alternative drug, pentoxyphylline, which is known to inhibit a cytokine named tumor necrosis factor a, to treat HIV infection. Since tumor necrosis factor a accelerates viral multiplication its inhibition should retard viral proliferation. Further, since the cytokine produces wasting, its use is currently recommended in the treatment of wasting associated with AIDS. So far nearly 40 individuals who are HIV positive and have no opportunistic infection at the time of presentation have been recruited in the trial. On a follow up that has been for up to periods exceeding one year there have been only two opportunistic infections, despite the fact that all patients had CD4 counts between 50 and 500/mm3. Serial CD4 counts have remained stable in most instances. Weight gain has been virtually universal with all patients, barring the two with opportunistic infections. Inhibition of tumor necrosis factor a leads to reduction of nitric oxide production and this was seen in a subset of patients. This study suggests that in our country where the vast majority of individuals cannot afford specific anti-retroviral therapy, use of alternative drugs could play a role in prolonging chronic phase of HIV infection. At a cost of less than Rs 10 per day this might become a useful form of therapy for preventing opportunistic infections in the HIV infected.
Dr. Ajay Wanchu, M.D., D.M
Department of Internal Medicine, PGIMER, Chandigarh
