GMHC Treatment Issues, Volume 10, Number 6/7 - June/July 1996
Dave Gilden

1. What antiretroviral regimen do you now recommend for your HIV-positive patients? How do you decide when to start antiretroviral therapy in an individual patient? When you consider developing a new treatment strategy for a patient, to what extent do you consider the patient's individual needs, lifestyle and ability to comply?

Preferred Regimens

Most use two drugs (25 percent) or choose between two or three drugs (25 percent) based on the patient's condition. The three drug combination includes a protease inhibitor. The most popular two drug combination is AZT plus 3TC mentioned as a choice for first-line therapy by 67 percent of participants. Reasons cited for this combination included tolerability (3TC), CNS penetration (AZT) and the potential for prolonged sensitivity or resensitization of the virus to AZT with the use of 3TC. AZT plus ddI is the second most popular combination (33 percent), followed by d4T plus 3TC (25 percent).

Hardy: I recommend combination therapy for all patients -- initially with ZDV/3TC, d4T/3TC or d4T/ddI. A protease inhibitor is added if a patient's initial HIV RNA is greater than 100,000 and the patient is agreeable to triple-drug therapy. (See accompanying article on HIV RNA viral load on pages 21-24.)

Mayer: My clinical practice has changed over the past year to never start antiretroviral therapy without a combination of drugs. The most common combinations that I would start with in an antiretroviral-naive patient would be AZT plus 3TC, or AZT plus ddI.

Katz: I start with AZT/3TC (AZT has best CNS penetration, and is a reasonably effective drug if tolerated). The AZT/3TC combination data looked better than that for AZT/ddC and while AZT/ddI may be comparable, ddI is difficult to administer. The upcoming Glaxo-Wellcome combined dosing of 300 mg AZT plus 150 mg 3TC should make compliance even better. 3TC is preferred from the onset also because of the reversal of AZT resistance and the fact that this drug is clearly the best tolerated of the reverse transcriptase inhibitors. In patients for whom compliance seems to be a huge issue, I might start with d4T/3TC; also for patients who simply won't take AZT.

Volberding: I recommend two nucleosides as the "standard" platform, either AZT/ddI, AZT/ddC or AZT/3TC. If the patient is intolerant of or refuses AZT then I use d4T/ddI or d4T/3TC. I add a protease inhibitor to this platform if HIV RNA is very high (greater than 100,000), the CD4 is very low (less than 100 or falling by more than 200 cells per year), the patient is symptomatic or if the two nucleoside analogs do not drop HIV RNA by more than half a log.

* Some institute three-drug combinations including a protease inhibitor at the very initiation of antiretroviral therapy.

Johnson: I start AZT plus 3TC in my HIV-positive patients independent of CD4 cell count. I start the AZT one month prior to the 3TC to make sure that it is tolerated. I have been adding indinavir to AZT plus 3TC for just about everyone, independent of CD4 cell count or viral load level.

Rhame: 3TC plus AZT plus ritonavir if early and the patient is willing to accept the chance of side effects. Otherwise, especially if the patient is on many other medications, 3TC plus AZT plus indinavir.

Giordano: For everyone with a viral burden greater than 10,000, AZT plus 3TC plus Crixivan or ritonavir. Ong: AZT plus 3TC plus ritonavir in those with CD4 less than 500, a recent decline in CD4 count or recent changes in clinical status.

* When they begin, some continue to consider monotherapy an option which is almost invariably ddI, cited as a first-line option by 19 percent of participants.

Vella: Monotherapy with ddI, for instance, is a reasonable alternative for patients who refuse a heavier regimen or show intolerance to AZT.

Yancey: Some patients are probably still appropriate for single-drug reverse transcriptase inhibitor therapy (not AZT) or a combo within this class.

* And those who stand out as particularly conservative, aggressive or alternative on when to use antiretrovirals.

Sonnabend: There is little data to support a rational decision on antiretroviral therapy. Since ACTG 175 and Delta are about the only source of evidence, although unpublished, I can recommend ddI even alone for people with under 400 CD4 cells whose status is declining (on the basis of 175). For those who are stable above 300, I don't know what to recommend and discuss this. Individuals who are stable can do very well without antiretroviral therapy. Most of my patients who are stable are content to do without antiretroviral therapy.

Bihari: The only antiretroviral regimen I use on a significant scale is AZT plus 3TC. I recommend it in general to patients with less than 200 CD4 cells. [This combination is particularly effective in] AZT-naive patients. Ninety percent of my patients are AZT-naive because of my past reluctance to use AZT monotherapy.

When to Begin

Most commonly, respondents use a combination of symptoms and surrogate markers (CD4 and viral load) when deciding to begin antiretroviral therapy (42 percent). However, the precise CD4/viral load values leading to initiating treatment varied greatly. Some clinicians described algorithms (a few are reprinted on page 7).

Mayer: The types of criteria that I utilize in recommending initiation of antiretroviral therapy include a pattern of consistent drop in CD4 count, a CD4 count less than 500 cells/mm3, an HIV load detected by plasma bDNA or a QC-PCR greater than 10,000 RNA equivalents per ml and/or constitutional symptoms or thrush.

Jäger: The criteria considered before starting an antiretroviral therapy are numerous and varied: CD4 count less than ca. 300 cells/ml for greater than one month and/or bDNA greater than 50,000 copies/ml greater than one month and/or the clinical impression of disease progression, e.g., recurrent minor infections, weight loss, lymphadenopathy and/or the occurrence of an OI.

Montaner: Therapy is begun if symptoms, a CD4 less than 500 or a viral load greater than 10,000 copies/ml is/are present.

Vella: Antiretroviral therapy is initiated when CD4 cell count is at or below 500/mm3 or HIV RNA titer exceeds 5,000 copies/ml or symptoms are present, irrespective of CD4 and HIV RNA values.

Hirsch: Decisions are made by the patient after discussion. Factors considered are HIV RNA, CD4 cell count, clinical status, lifestyle, ability to comply and cost, among others.

Volberding: All symptomatic HIV-positive; all patients with CD4 less than 500; all patients with CD4 greater than 500 and HIV RNA greater than 50,000; all patients who, after discussion, wish to be treated.

Para: Start when the patient is ready and the CD4 is less than 500 if the viral load is greater than 10,000 or when the CD4 is greater than 500 if the viral load is greater than 100,000.

However, many begin their patients on therapy based predominately on CD4 counts (25 percent), but this may partially be due to the limited availability of the viral load tests in certain areas.

Birnbaum: I usually recommend starting therapy below 500 CD4 count but have given it to some patients felt to be in the very early stages of infection (less than one year) with more than 500 CD4 cells. Much of this depends upon the patients' interest and willingness to take drugs.

Rhame: If their CD4 is below 200, I press them hard to start. With CD4's between 200 and 500, I press them gently to start. If their CD4 is above 500, I'll start if they press me.

Fewer use viral load alone (17 percent) as a reason to begin therapy.

Hardy: HIV RNA levels greater than 5,000 copies/ml are associated with decreased survival and increased risk of developing AIDS. I use viral load measurements greater than 5,000 /ml as my starting point to initiate antiretroviral therapy regardless of CD4 cell counts or percent.

Katz: Starting therapy: I get a viral load (bDNA) on every new patient -- anyone with over 100,000 gets two reverse transcriptase inhibitors immediately, anyone with 10,000- 100,000 gets told by me that if I were them, I would start, but they might want to repeat/observe for a while. For under 10,000 I repeat in three to four months, but for the patient who absolutely wants to be maximally aggressive at whatever T-cell/viral load, I would give two drugs without hesitation at this time.

Patient Considerations

Essentially everyone considered the patient's lifestyle, wishes or compliance when prescribing therapy.

Mayer: The most important thing for any patient to feel is that he or she has a great number of choices and that no choice is to be considered permanent and that all choices should be re-evaluated in light of new information. It is essential for the patient to feel that he or she is in control and that the medical providers are allies in their care. Our clinical encounters should be times when they ask as many questions as possible and patients only elect to begin or add treatments once they feel that they have enough information to make an intelligent and informed choice.

Jäger: The patient's lifestyle and needs, but, above all, ability to comply, play a major role in developing a treatment strategy; without the patient's cooperation, even the best possible treatment is doomed to end in frustration and failure.

Abrams: I usually prescribe antiretroviral therapy to patients who ask me for it. They usually know what they want and ask for it specifically.

2. What factors would enter into a decision to switch or stop antiretroviral therapy in an individual patient?

Toxicity and adverse events were mentioned most frequently as reasons to stop or switch therapy (78 percent), followed by a combination of symptoms and surrogate markers (64 percent). Patient's request was cited by 22 percent of participants.

Mayer: Any subjective experiences that might be considered toxicities have to be at the top of the list, including nausea, fatigue, weakness, headaches, etc. Since we know that with some drugs the experiences may be highly transient (e.g., such as when individuals start AZT), I may counsel the patient to see if they can tolerate the symptoms over several days. Other symptoms may resolve after a drug holiday and reinstitution of the treatment at a lower dose level (e.g., sensory neuropathy with d4T), but often these symptomatic toxicities necessitate changing treatment independent of clinical responses. Other factors that might lead to changes in treatment would include a rapid drop in CD4 count, a rapid increase in HIV load, the onset of new minor (thrush) or major opportunistic infections and/or constitutional symptomatology.

Johnson: I stop therapy based on an individual's compliance and tolerance of a particular regimen. Most of my patients tolerate therapy across all HIV-1 disease stages. I have been switching therapy mainly based on symptoms suggestive of viremia, although I will probably obtain a viral load test more often in the future to decide if a person is failing from a serologic standpoint.

Jäger: Factors which would lead to a change or stop in antiretroviral therapy include: side effects not tolerable and/or treatable (e.g., nausea, vomiting, headaches, (poly- )neuropathy), WHO grade three or higher changes in laboratory parameters (GOT/GPT, AP, anemia, CD4, viral load greater than at baseline, etc.) and/or during an acute opportunistic infection. The antiviral therapy is then re-started as soon as possible when the OI is stable.

Katz: Intolerance is an easy one -- if they can't take the drug, I switch. If neuropathy occurs on a 'D-drug' [ddI, ddC, d4T], I stop completely (assume they're on 3TC already, as most of my patients would be), push AZT to the extent it can be. I have seen only a few patients (less than 2 percent) who are intolerant of all reverse transcriptase inhibitors. For a patient who can take only 3TC (e.g., AZT-induced headaches/nausea and 'D-induced' neuropathy) I start a protease inhibitor as the second drug regardless of viral load/T-cells.

Viral load -- anytime it goes over 100,000, therapy must be switched. If it was undetectable, however, and now is above 10,000, I will propose a switch.

Clinically -- let's not forget the patient with sustained low viral load and tolerating meds well but who is developing new symptoms or T-calls falling steadily (unlikely if viral load is low). I would propose adding a drug here, probably a PI if already on two reverse transcriptase inhibitors.

Hardy: Poor compliance, especially on protease inhibitors. It is probably better to be on no antiretroviral therapy rather than suboptimal dosing.

Youle: Toxicities which occur on rechallenge or are not amenable to reasonable supportive therapies.

A number of doctors discontinue therapy in very late stage patients.

Carpenter: We make the decision to stop whenever side effects of antiretroviral therapy exceed potential benefits of therapy. This is fairly common in very advanced illness, when the need to treat CMV, MAI and to prevent PCP is more important than the continuation of antiretroviral therapy.

Cooper: I stop therapy when no further benefit is demonstrated, there's too much toxicity or there's more benefit from prophylaxis [alone].

Jäger: Although it is difficult to decide, patients who are at the "point of no return," i.e., show no positive response to medications, have several OIs simultaneously and/or are, in general, very ill are no longer treated with antiretroviral agents.

Some doctors consider discontinuation of therapy, when treatment reduces viral load to a very low level, and stays there when treatment is stopped.

Cooper: I stop therapy if a patient becomes asymptomatic with viral load below 10,000 off therapy.

Cohen: Some buzz is starting on using powerful regimens to get virus load to undetectable for about one month and it [viral load] staying low even when drugs are stopped.

3. Are you making use of HIV RNA viral load assays? If so, what absolute levels or changes do you consider significant? How often do you recommend these tests? How does the availability of viral load assays alter your treatment strategy?

Eighty-three percent have access to viral load testing. With the exception of one physician who believes there is little evidence which supports "early intervention," all those who have access use viral load in making treatment decisions. Those who have had access the longest appeared to have more confidence in its use as a reliable indicator of when treatment was necessary and/or of treatment response. This greater confidence in turn yields more aggressive use of these assays. Many who cannot offer the test cited payer constraints and managed care obstacles and would like broader access to help in patient assessment and response to therapy.

Viral load is most commonly checked before initiating therapy, four to eight weeks after initiating therapy and then every three or four months. Of those who use viral load, approximately two-thirds offered their view on what absolute levels or changes were considered significant and these were quite varied. Six believed levels greater than 5,000 were significant; four believed 10,000; one believed 50,000; three believed 100,000; one said no absolute level was significant; one said that any detectable virus was significant. In terms of changes, one believed that a change of 0.3 log was significant; eight believed 0.5-0.6 log; two believed 1.0 log; one said no absolute level of change was significant. Two respondents stated that the goal of therapy was to keep viral load below detection; two said the goal was to keep it below 5,000; four liked to keep it below 10,000.

Here are examples of viral load's impact on some specific strategies.

Mayer: I am starting to use HIV RNA viral load assays more frequently and am tending to obtain a baseline value on each new patient that I see. I consider an HIV RNA viral load level of greater than 10,000 copies/ml to be significant and have tried to use antiretroviral therapy to keep the level below that threshold. I do not use the viral load to the exclusion of other important clinical markers. However, I would consider an increase in the HIV load of a log to be of significance and to warrant re-evaluation of the current antiretroviral regimen that the patient is taking.

Collier: I like to see HIV RNA that becomes undetectable. I am more aggressive with treatment at higher CD4 counts if HIV RNA is high.

Bihari: I recommend this test every three months in all of my patients. I consider a change of 0.5 log or more significant enough to influence treatment decisions.

Rhame: I use the level for starting considerations to "adjust" the CD4; e.g., CD4 of 250 with load of 100,000 would adjust to CD4 200. For change, greater than 0.5 log seems significant.

Standish: I consider a 0.3 log unit drop significant. I recommend them every three months and I am using this test more frequently in patients with whom I am doing informal patient-oriented single-subject studies of herbs.

Some physicians stressed the extreme importance of monitoring and treating viral load. Many believe it has changed their approach to the treatment of HIV.

Hardy: I've been making use of viral load assays for 20 months now and recommend antiretroviral therapy for HIV seropositive persons with HIV RNA greater than 5,000/ml. Persons with HIV do clinically better with lowering their viral load, especially with dramatic decreases from greater than 50,000/ml to less than 500/ml. It's amazing and wonderful to see. A ray of optimism is emerging.

Braun: Any amount of detectable virus is significant. The availability of viral load along with the susceptibility assay [viral genotyping] heighten the certainty of effectiveness of treatment.

Giordano: Check it six weeks after altering antivirals and every three months when a satisfactory viral load is achieved. Treat the viral load!

Dieterich: I use viral load to make all treatment decisions, and [the goal is to] keep it below 5,000 copies/ml.

Vella: We believe that viral load is the most reliable marker for disease progression and recommend therapy when HIV RNA exceeds 5,000 (possibly 10,000) copies/ml of plasma. Patients with more than 30,000 copies are at high risk of progression. To be considered as successful, antiretroviral treatment should cause at least a 1 log decrease in viral load. However, not only the magnitude is important, but also the durability of the response.

Katz: Over 100,000 necessitates beginning or changing therapy. Under 10,000 necessitates no change, but between 10,000 and 100,000 I feel the patient out for how aggressive he/she wishes to be. I'm prescribing more drug with higher T- cells than I would have in past.

Barriers to access continue to be a problem. This may change with the recent U.S. FDA approval of the Roche Amplicor test.

Birnbaum: Viral load assays are not available to my patient population [Kings County Hospital, Brooklyn] so I have not made a single treatment decision based upon them. I look forward to the opportunity to use these tests.

Brosgart: A major problem is that managed care doesn't want to pay.

Johnson: I think it is expensive to get two baseline viral load tests, and I sometimes can only justify getting a viral load test four weeks after initiation of triple therapy.

Ong: We see Medicaid patients almost exclusively in an inner city environment. HIV RNA viral load assays are not presently Medicaid reimbursed.

Para: Without FDA approval and with lack of payment, I am not using RNA to the fullest extent.

Jäger: In patients on treatment, we tend to test every six to eight weeks. Financially it is difficult to justify testing more often, although being able to document monthly changes would surely be beneficial.

But some practitioners raised a number of issues about the use of the test.

Stein: A change of 0.5 log [three-fold] is needed to be significant given the test's and biologic variability. This assumes that the specimen was actually handled correctly, that the plasma or serum is used consistently and that the same assay is being compared. In follow-up, it is not as clear. It is most useful when one is unclear whether therapy is working or not. [But viral load monitoring] probably doesn't add a lot to the follow-up of asymptomatic and CD4 stable patients.

Para: I don't feel comfortable about non-research handling and reliability of the result. Research specimens are carefully processed and quality controlled. Others are sent out. RNA is useful for prognosis and assessing response to therapy but I am unsure what absolute values to use. You need a three- to five-fold change in a single patient to believe it's a real change.

Cotton: I'm using viral load assays but so far my practice is far more 'art' than science. I'm using the test to decide to switch or add therapies but, once again, only in a qualitative way.

Sonnabend: I have no evidence that this [viral load] means anything in patients above 100 CD4 cells. I don't know how to use this test for treatment decisions but do so anyway in order to learn something. It is obviously important as a prognostic indicator. I'm worried that now that viral load tests are available, that the results will influence treatment decisions. There is no evidence that's convincing that early intervention makes much difference. So why should this [test] change that?

4. When do you recommend the use of protease inhibitors? What sort of experience have you had with these drugs? (Please relate your overall impression of their effectiveness and also patient tolerance and compliance with dosing schedule, mentioning distinct characteristics of each particular drug.)

The majority (66 percent) of physicians cited a combination of critical CD4/viral load levels or changes as the reason to initiate protease inhibitor treatment. Symptoms or patient request was cited by 8 percent, while only 8 percent always use protease inhibitors as first-line therapy. One participant stated that he never uses protease inhibitors and another questioned the clinical relevance of the increased CD4 count.

Approximately 50 percent of survey participants commented on specific protease inhibitors. While indinavir and ritonavir were uniformly considered effective, saquinavir was considered too weak or too poorly bioavailable to be effective in its current form (85 percent). Indinavir and saquinavir were almost universally considered well tolerated while 89 percent of comments on ritonavir noted its poor tolerability (mostly gastrointestinal) or difficult drug interaction issues. Some expressed hope that a slower dose escalation strategy over two weeks would reduce these side effects but others noted that these GI adverse effects are worse than what was seen in the clinical trials despite the slow dose escalation. Four physicians noted the difficulty with indinavir access through Stadtlanders or problems with the Merck Patient Assistance Program.

Overall, one might characterize the response to protease inhibitors as tempered optimism. The increased CD4 counts and decline in viral loads were viewed as encouraging but duration of response was questioned. Drug interactions (particularly, ritonavir), side effects (particularly, gastrointestinal problems with ritonavir) and compliance requirements (particularly, coordinating meals with thrice daily indinavir) were frequently noted as problems.

An example of aggressive protease inhibitor use.

Giordano: [I use] protease inhibitors almost always and have extensive experience. Tolerance: ritonavir is excellent after four weeks if prescribed correctly (dose escalate over two weeks); indinavir and saquinavir are excellent. Efficacy: saquinavir is not effective; ritonavir and indinavir are effective. Advanced disease is reversible if protease inhibitors are used.

Most add protease inhibitors when they believe nucleosides alone are not enough.

Cooper: [I use protease inhibitors in those] failing double nucleosides and have extensive experience. These drugs are very effective and generally well tolerated. Compliance is good if careful explanation is given to the patient. Saquinavir is less potent and well tolerated; indinavir is potent and well tolerated; ritonavir is potent and slightly less tolerated.

Jäger: We recommend their use as a monotherapy when other regimens are not tolerable and/or effective or we combine them with other antiretrovirals when those begin losing their effect as seen in rising bDNA levels and/or falling CD4 counts.

Cotton: I am generally reserving protease inhibitors for patients with less than 300 CD4 cells who have viral loads greater than 10,000 despite nucleoside therapy (usually AZT/3TC).

Montaner: Given the issues of cost, toxicity and drug interactions, I reserve them as second-line therapy.

Dieterich: I have vast experience with protease inhibitors and use them when the patient's T-cells fall below 500 with a viral load greater than 20,000. Saquinavir is not toxic but not effective. Norvir is effective but toxic. Crixivan is the most effective and least toxic.

Some concerns.

Bihari: I have chosen to recommend the avoidance of protease inhibitors until the Roche/Abbott study of the saquinavir/ritonavir combination has shown what doses of each are safe in combination.

Matula: [Use when] patients fail other combinations. There are good increases in CD4 counts but I'm not sure how effective. One female patient went from CD4 of 21 to 380 and still broke through her PCP prophylaxis.

Vella: Protease inhibitors appear to be highly effective. However, their use has some drawbacks, especially when they are given to advanced patients, who are likely to assume many other medications. [Drawbacks include] the high number of capsules that must be swallowed and the side effects (especially the gastrointestinal disturbances with ritonavir).

Mayer: I have to review the patient's medication list and discuss with him or her their eating patterns, given the need to administer indinavir on an empty stomach or with a very light meal. Because of the issue of drug compliance in relation to meals, several patients have been started on ritonavir. I have had complaints about "metal mouth" and gastrointestinal discomfort with both ritonavir and indinavir so I really cannot say one drug is better tolerated than the other.

Sonnabend: I only prescribe protease inhibitors for people with less than 100 CD4 cells who are symptomatic, as I have good evidence for benefit in this population. Why waste them (with resistance developing) in healthy people who may need them later? They are more toxic, particularly GI toxicity, than generally presented, particularly ritonavir which also has the worst problem with interactions with other drugs.

And some comments on specific agents.

Saquinavir: Most felt the drug to be safe, but not very effective. Respondents were hopeful about the new formulation

Braun: Thirty percent to 60 percent of patients respond to saquinavir. Collier: I rarely use saquinavir unless other protease inhibitors are contraindicated.

Montaner: Saquinavir is the less desirable of them due to poor bioavailability. Katzenstein: Awaiting for formulation with increased bioavailability.

Volberding: Saquinavir is easy to use, but there are few indications for the current formulation due to poor levels. I'm watching the new formulation closely. If higher levels, will we see more toxicity, drug interactions?

Indinavir: Almost everyone is pleased with its efficacy and patient tolerance, but there's some frustration with the Stadtlanders' distribution program.

Carpenter: I have had 20 months of experience with indinavir. Patient compliance has been excellent! Hardy: Efficacy is excellent, RNA declines 99 percent to 100 percent and it is generally well tolerated. There is a rare increase in total bilirubin. I have seen two patients with kidney stones, but patient acceptance is good.

Katz: Indinavir clearly has the best profile of ease of dosing and patient acceptance presently. It's the cheapest by far of the three (30 percent price advantage versus ritonavir).

Volberding: Indinavir is the current 'winner' in terms of toxicity/benefit balances. Eight-hour dosing a real problem with compliance (especially the need to avoid meals). Stadtlanders is a very cumbersome bureaucracy.

Johnson: My impression is that indinavir is well tolerated, although it has been difficult to obtain this drug through the Merck Patient Assistance Program.

Ong: Because of the difficulty in indinavir access, I have used ritonavir.

Rhame: It's a big hassle getting indinavir.

Yancey: Coordination with meals is difficult. Less indinavir is prescribed secondary to the monopoly by Stadtlanders.

Ritonavir: Almost everyone is impressed by the efficacy but most are disturbed by the toxicity and drug interactions.

Saag: Ritonavir is OK if patients can tolerate it. There are more patients with intolerance than we observed in the studies. I don't know why.

Collier: Tolerance to ritonavir has been a problem even with the initial gradual dose escalation.

Ong: Ritonavir: nausea, vomiting and diarrhea can be problems. Hopefully, the new starting dose regimen will be better tolerated.

Braun: Only 30 percent to 40 percent of patients tolerate ritonavir even with an empowered patient tapering up over two weeks.

Katzenstein: Ritonavir is a great concept but a difficult drug over long term in advanced patients because of interactions with other meds.

Starrett: Wasted patients need to eat so the indinavir schedule may not be optimal. Patients who don't have regular schedules of medications would be best with twice daily dosing of ritonavir.

5. Do you prescribe or do many of your patients take on their own additional, unapproved anti-HIV therapies (for example, acyclovir, hydroxyurea, N-acetylcysteine, or vitamin supplementation)? How are they used and what is your evaluation of their effectiveness?

With the exception of two physicians, participants do not, themselves, actively prescribe alternative therapies. However, 72 percent have patients who use alternative therapies. The consensus was that if alternatives did not seem to have negative effects, physicians did not have a problem with patients using them. Of those who mentioned alternative therapies, 42 percent mentioned acyclovir while 38 percent mentioned vitamins. But of those who mentioned acyclovir only nine participants actively recommended its use.

Abrams: Most of my patients take acyclovir with or without other antiviral drugs. I believe HSV probably upregulates HIV and have thought it wise to suppress it.

Katz: I still recommend it, especially in persons who have a history of herpes and patients who can't tolerate many therapies and have low T-cells.

Mayer: If patients have problems with herpes simplex recurrences and the costs of acyclovir isn't a disincentive that leads to underutilization of other medications, I am comfortable based on the data from several studies that suggest a survival benefit, with maintaining patients with CD4 counts less than 100 on acyclovir 800 mg, five times at day. On the other hand, because several other studies did not corroborate this survival benefit, and given the drug's cost and concerns about compliance with polypharmacy, there are many patients for whom I do not recommend acyclovir when their CD4 counts drop below 100 cells/mm3.

Sonnabend: I have always believed that acyclovir was potentially beneficial since I have believed that herpes viruses are important factors.

Braun: We are switching all patients from higher doses to acyclovir 400 mg twice daily.

Several physicians offered opinions on some alternative therapies.

Birnbaum: I have found that Chinese herbs when properly prescribed by a Chinese herbalist have been very effective treatments, mostly for fatigue and wasting. One patient used kambucha mushrooms to treat PML and had a remission of signs and symptoms.

Giordano: NAC and acyclovir are not effective; hydroxyurea is effective but use it only on study; vitamin supplementation is of unknown efficacy.

Cooper: Hydroxyurea: I'm not impressed with the results. NAC doesn't work.

Katz: Hydroxyurea: I wish more patients would glom onto this. I think it's clearly worth a shot, but I have no one on it. I'm eager to see the studies. I recommend vitamin/mineral supplementation for all patients at any T-cell level (see Baum et al, Micronutrients and HIV Progression, J. AIDS, 1995). I have nothing more than anecdotal experience that patients on vitamin/mineral supplementation do better, but they are generally doing 42 other things simultaneously.

Sonnabend: NAC and antioxidants can't hurt.

Braun: S-7 flavor tea was used once and worsened the patient's renal status. QoXing was used once and was poorly tolerated. Patients have abandoned NAC. We encourage multivitamins but are neutral on Vitamin B12 and antioxidants. With DHEA, we see no objective improvement but it's hard to monitor. Thalidomide is excellent for ulcers and great for diarrhea with some limited improvement in wasting.

Two physicians stood out as using alternative therapies as the foundation for their anti-HIV therapy.

Bihari: I prescribe acyclovir 3,200 mg/day to all HIV- positive patients. I also prescribe naltrexone 3 mg at bedtime to all patients regardless of CD4 level. Naltrexone stops the CD4 decline in 80 percent of patients and in 90 percent of those with more than 200 CD4 cells. I also recommend NAC 600 mg three times daily and several antioxidants to all patients.

Standish: Now that viral load testing is readily available for many patients, I am trying botanicals, homeopathics and hyperthermia. Thus far, nothing I've tried has substantially reduced viral load, with the exception of high dilutional growth factors and cytokines. All of my patients are using alternative methods. Acupuncture is the most common and perhaps the most useful. I have yet to see anything that produces dramatic improvements of immune markers such as CD4. We are using a lot of DHEA too, if a patient's serum levels are low or low normal. It seems to help overall energy. We hope to be doing a small trial of DHEA soon. We are working hard at Bastyr's clinic to keep the intestines healthy using acidophilus, glutamine, NAC, UltraClear Sustain, beta carotene, Vitamin C, Vitamin E, quercitin. Also we're using CoQ10 more and more.

6. Do payer constraints influence your treatment decisions (for example, Medicaid, ADAP or formularies)? Is so, please explain. Of total participants, 69 percent cited payer constraints influencing treatment decisions.

Of the seven physicians from outside the U.S., three had no problem with payment: one from each of Italy, Germany and Australia. One physician from Canada, one from France and two from the U.K. cited payer constraints. Within the U.S., 72 percent cited payer constraints. Many cited that Medicaid is far better than ADAP, where choices are much more limited; however, Medicaid was often cited as the reason for not being able to use viral load assays.

Examples of problems.

Brosgart: Yes, yes. Many payers refuse off-label drug use. Managed care has prior authorization and restricted formularies. ADAP has a long lag between licensure and inclusion on its formulary. Managed care has fixed pharmacy dollars but lots of new experimental drugs. The HIV specialist is being squeezed by managed care. We need to effectively advocate to treat patients. Often we're not considered primary care, as a way of keeping patients out of health plans. Delivering comprehensive, coordinated high quality care costs more up front but saves on big ticket items (hospitals, ER).

Volberding: We need to find a way to get HMOs to provide HIV centers of excellence without fear of adverse selection.

Saag: Absolutely, I live in Alabama. Medicaid is inaccessible for most (need less than $479 a month income; net worth less than $3,000). Ryan White: no Title I; limited Title II/III. We spend hours per week applying for assistance.

Abrams: Medicaid usually pays. ADAP has just put 3TC on the formulary. No protease inhibitors are yet on in California, but most of my patients utilize the federal insurance program, not ADAP.

Birnbaum: Most of my patients are Medicaid covered. If they have Medicaid, there's no problem prescribing these meds. If they are covered by ADAP only, my treatment choices are limited to what ADAP covers. If they are uninsured, I am limited to my hospital formulary of AZT plus ddI only plus a supply of a few months worth of 3TC which was donated to my clinic.

Kessler: Yes, viral load is not paid for by public aid or Medicare.

Ong: We cannot use HIV RNA plasma levels

Para: Yes, we don't get RNA on these [Medicaid, ADAP] patients unless they are in trials. We cannot get protease inhibitors on ADAP.

Stein: Medicaid has, at present, better coverage than [New York] ADAP or the VA for antivirals. HMOs can be a problem.

Katlama: We are very concerned about the long-term cost of treatments. I do not use very expensive drugs which don't have optimal efficacy. Even more difficult for alternative medicine.

Standish: Yes, payer constraints severely and adversely influence what treatments are possible for many of my patients. It is rare that third party payers will reimburse for natural and alternative medicines. Some insurance companies don't cover viral loads, or not as often as I think medically necessary. In Washington State, alternative medicine is now being covered by insurers, reluctantly and incompletely. Being part of the insurance game presents even more constraints. We have a horrible system in the United States. Some good news.

Katz: We have a very liberal formulary at Kaiser, and every HIV-approved drug is on it, so this is not a consideration.

Cohen: [Massachusetts] ADAP covers all antivirals except indinavir (which we get instead from Merck). The only other rare problem is that ADAP doesn't cover unlimited fluconazole and acyclovir.

Jäger: Fortunately, the social medical system in Germany allows (nearly) complete coverage of all necessary medication and/or therapy regimens. Thus, all of the approved antiretroviral substances including protease inhibitors can be prescribed, also in combination.

And in a word . . .

Rhame: Only when they won't pay.

B. Opportunistic Infections

7. Do you recommend prophylaxis for CMV, MAC or fungal infections? If so, with what agent and in what patient population?

For opportunistic infection prophylaxis, the trends were very clear. Only 11 percent prescribe primary prophylaxis for fungal infections. Concerns about azole resistance were cited. Approximately 17 percent prescribe prophylaxis for CMV, most commonly at CD4 counts below 25. The negative CPCRA oral ganciclovir CMV prophylaxis study (see Treatment Issues, October 1995, page 10), the large number of pills, toxicity and cost were the most common reasons cited for not prescribing prophylactic oral ganciclovir.

Primary prophylaxis for MAC, conversely, was quite popular (83 percent). Of the 22 participants who cited their choice of therapy, 82 percent prescribe macrolides (clarithromycin or azithromycin). Recent data on macrolide prophylaxis was cited by many. A few physicians described a recent switch from rifabutin to macrolides and some cited difficulty in using rifabutin with the protease inhibitors as the reason for a macrolide preference. Of the 21 physicians who described when they start MAC prophylaxis, eleven initiated therapy at a CD4 count below 50, seven started below 100, and two started below 25.

Those who are most aggressive with prophylaxis are also the most conservative with antiretroviral therapy. One physician cited occupational risks for fungal infections.

Although MAC prophylaxis was common, there were some concerns.

Katz: Until recently, I have used rifabutin (since its 1992 approval). Then with the protease interactions, I started using clarithromycin. Now, it's all a big wash. More and more at Kaiser our infectious disease specialists are suggesting not using any and either getting blood cultures every three months or treating at the first MAC symptoms. It has become a reasonably treatable condition nowadays and patients generally prefer to have one less drug to take; so does the health care economy. The effect this [prophylaxis] will have on ultimate development of MAC and possibly cross-resistant clarithromycin-azithromycin strains remains to be seen. If we lose the ability to fight this infection with either of these two drugs, we're back in the mid-80s--with four to five drugs, IVs and still not great results.

Johnson: I have not been routinely recommending prophylaxis for CMV, MAC or fungal infections. I am concerned that many of these agents may interrupt or alter levels of antiviral therapies. I have mainly focused on maximal antiretroviral suppression, rather than starting prophylaxis for these opportunistic infections. However, my thinking has changed based on the data from Dr. Diane Havlir and the California Collaborative Treatment Group. I will likely start azithromycin weekly to prevent MAC. I am also very aggressive about early initiation of clarithromycin and ethambutol for empiric treatment of MAC.

Brosgart: Yes, in those with CD4 less than 75. First choice is a macrolide (azithromycin is number 1; clarithromycin is number 2); second choice is rifabutin.

Saag: For CD4 less than 25, take two drugs: clarithromycin and ethambutol.

Bihari: If the CD4 cells are below 100, Biaxin 500 mg/day with ethambutol, 800 mg/day to prevent MAC.

CMV prophylaxis.

Abrams: No, I agree with the CPCRA study.

Brosgart: All patients with CD4 less than 100 are seen by an ophthalmologist every three months. No oral ganciclovir prophylaxis: it's of limited benefit, too toxic and expensive.*

Mayer: Based on the CPCRA study of primary CMV prophylaxis, we do not routinely start empiric therapy with ganciclovir based on the CD4 count criterion. We hope that in the near future that quantitative CMV measurements in the plasma will enable us to predict which patients are most likely to progress with CMV retinitis.

Bihari: In those with CD4 cells below 150, start acyclovir, 4,800 mg/day to prevent CMV infections.

Fungal prophylaxis.

Brosgart: Fungal prophylaxis only if severe, chronic, recurrent disease.

Bihari: In patients with CD4 cells below 200, Diflucan 100 mg/day to prevent cryptococcal meningitis.

Rhame: Fluconazole for CD4 less than 100 . . . more anti candida effort required [for female patients]. Prevention of histoplasmosis as a rationale for azole prophylaxis is not adequately appreciated.

Hardy: Only for those with CD4 less than 100 and chronic exposure to fungi, coccidiodomycosis (gardeners, construction).

8. Do you recommend TB prophylaxis for patients who are HIV- positive and anergic?

Only three participants answered this question, affirmatively. Some of those who answered, no, explained that they reserved prophylaxis for those with high risk histories or a positive PPD (skin test for TB exposure).

Mayer: We definitely recommend TB prophylaxis of INH with Vitamin B-6 for one year for patients who are HIV-positive and anergic in our community, given our experience with several recent outbreaks.

Ong: Yes, for patients who receive directly observed preventive therapy in our drug treatment centers.

9. What treatments do you utilize to reverse weight loss and wasting (nutritional, human growth hormone, anabolic steroids, thalidomide or other anti-TNF compounds, etc.)?

The most common interventions for weight loss are anabolic steroids (72 percent) and nutritional counseling/supple- mentation (67 percent). Often mentioned were Megace (42 percent), Marinol (33 percent) and human growth hormone (19 percent).

Although these agents were used by many, views on their utility were anything but uniform.

Brosgart: Nutritional counseling; rule out hypogonodal and hypoadrenal. Deal with nausea and oral ulcers. Try to give most meds with meals. I love thalidomide. I like to put my patients in trials so we can learn more about treatment or preventing weight loss and wasting. Sometimes patients are just losing weight because they don't have food.

Cohen: New antivirals are clearly effective as an antiwasting treatment. I have seen big weight gains with ritonavir. A few patients have done thalidomide but had more side effects than benefits.

Mayer: Our first line of defense is enteral supplementation tailored to a regimen that patients can maximally tolerate. We also recommend that the patient engage in weight bearing exercise in order to maximally benefit with a positive anabolic reaction.

Bihari: In general, identifying a slowly developing OI that is causing weight loss and treating it is the most common approach. AZT plus 3TC reversed weight loss and wasting in patients more effectively than growth hormone, thalidomide, Trental or anabolic steroids.

Anabolic steroids, particularly testosterone, are the most common pharmaceutical interventions for wasting but physicians did not describe their effects in any great detail. Some mentioned oxandrolone, one mentioned decadurobolin.

Volberding: Anabolics are the easiest way to get some benefit.

Cohen: Intramuscular testosterone with or without decadurobolin in many (male) patients. I'm considering oxandrolone. Human growth hormone's price was cited as a problem. Volberding: HGH works, but it's way too expensive.

Brosgart: I rarely use rHGH; it's expensive and of limited benefit. It's a last resort.

Cohen: I don't use HGH. It's not clearly worth the price.

Mayer: In patients who have lost more than 5 percent of lean body weight, we begin discussions about the possibility of utilizing human growth hormone, which to date has impressed us as the most effective agent in reversing catabolism. Megace and marinol.

Volberding: Megace: poor side effects and all fat. Marinol: not too effective but some like it (many more prefer marijuana which is available in SF through a local buyers' club).

Brosgart: We use Megace and Marinol. Cohen: I will use Marinol/Megace to improve appetite (as well as suggest marijuana if helpful). An alternative approach.

Standish: We are beginning to try high dilutional insulin growth factor and Sea Cure protein supplements. I think early total parenteral nutrition [TPN] helps a lot. It's hard to get other doctors to see the wisdom of early TPN.

C. General

10. If you see significant numbers of women or children with HIV, can you comment on age or gender-related differences in treatment of the virus or opportunistic infections?

Unfortunately we received little or no responses about treating children. The vast majority of those with experience in treating women believed there was little significant difference. The need for diligent screening for vaginal infection (particularly candidiasis) and cervical cancer were emphasized. An increased incidence of oral/esophageal candidiasis and a decreased incidence of KS were noted. Two physicians believe that women present with more advanced disease.

Women.

Bihari: I see a lot of women who represent 30 percent to 35 percent of my practice. Apart from the obvious differences (i.e., need for frequent PAP smears, alertness to and aggressive treatment for vaginal infections and pregnancy issues), I find no differences in the treatment of the virus or OIs.

Brosgart: Women are 25 percent of my population. There are few differences when adjusted for CD4. We often must weight-adjust meds.

Carpenter: I have not noticed gender-related differences in treatment of the virus. OI treatment is also similar, the only difference being the gender specificity of vulvovaginal candidiasis.

Johnson: Unfortunately, due to the demographics of HIV-1 infection in Alabama, I see a significant number of women (approximately 50 percent of my clinic). I think that these women tend to get diagnosed at a later disease stage, but that their complications are not terribly different from those of adult men. The women in my clinic do seem to have more difficulty with vaginal candidiasis during antibiotic therapy for other infections. They also tend to have unrecognized concomitant STDs such as human papillomavirus.

Mayer: With regard to the major opportunistic infections that men can develop, the women seem to develop them at a similar rate and do not have substantively different clinical patterns with these opportunistic infections, except for a slightly increased propensity toward mucosal candidial infection, resulting in a slightly higher annual rate of candidial esophagitis. The major clinical differences in HIV- infected women compared to men is that there is substantial gynecological morbidity that the women experience in the course of their HIV infection. With meticulous gynecological care, invasive cervical carcinoma is rare; however, atypical PAP smears are common and require careful follow-up with quarterly PAP smears and colposcopy when abnormalities persist. Prompt, but specific surgical procedures can help avert wider spread of localized cervical neoplasia. Several of my colleagues have seen women with recurrent pelvic inflammatory disease. Traditional sexually transmitted diseases have been uncommon among the HIV-infected women that we followed, but recurrent candidial vaginitis, bacterial vaginosis and trichomoniasis may be common causes of clinical discomfort and require prompt diagnosis and treatment. Several of the women that we follow have recurrent sinusitis and pneumonia but the prevalence and incidence rates for these conditions have not been radically different from that of demographically similar men.

Saag: We have no data about menopause.

Cotton: I do think there are emerging issues in antiviral treatment of women in terms of how to treat women with plans for conception, etc.

Standish: Women are simply much sicker when I begin working with them. They also seem to tolerate less well anti- retrovirals, ganciclovir and MAI regimens.

Volberding: Women present a different array of social and financial issues.

A note about adolescents.

Birnbaum: In general, it has been historically difficult to get adolescents to take antiretroviral medications. More recently, since the advent of widespread use of combination therapy many actually have started requesting to start on combination therapy and to use protease inhibitors. Many are reluctant to use OI prophylaxis but usually do so, at least for PCP, after they have been given the information to make an educated decision. As a general rule I try to prescribe medications that have once or twice a day dosing, as this tends to improve compliance.

11. Do you have any further observations from your practice that you would like to report (particularly findings that are not commonly discussed)?

Carpenter: A comprehensive care program in a single site is of critical importance, I think, with maintaining adequate long-term compliance with any regimen.

Johnson: Indeed, the majority of my patients have more problems related to wasting syndrome and ultimate demise than from opportunistic infections. I also think that IV amikacin is the drug of choice for MAC relapsed episodes and give a four-to-six week course on top of oral therapy for relapses. By giving this drug intravenously by home health nursing five days of the week for four to six weeks, I have been impressed that several patients have resumed excellent quality of life. Finally, it is my impression that patients with CD4 less than 10 cells/mm3 can tolerate double and triple antiretroviral therapy well, despite prior observations about enhanced toxicity. I think that it is a myth that patients with advanced HIV-1 disease cannot benefit from antiviral therapy, which can reduce the frequency and severity of their opportunistic infections. Many of these patients have survived for years with excellent quality of life despite their advanced disease stage.

Bihari: My long-term patients very rarely develop OIs and 85 percent to 90 percent have long term stability of CD4s. The three major factors are: 1) low dose naltrexone; 2) aggressive OI prophylaxis as described in question seven; 3) the effectiveness of AZT plus 3TC in AZT-naive patients and the fact that 90 percent of my patients are AZT-naive because of my past reluctance to use AZT monotherapy.

Saag: Patients are living longer with new problems: fluconazole-resistant cryptococcus after two to three years of secondary prophylaxis and resistant CMV. There may be less HIV dementia. There is a significant change in demographics: more poor, more African Americans, more women, more heterosexuals (despite the Wall Street Journal!).

Para: I stress the importance of regular exercise in reducing symptoms.

Standish: We have done a little experimental work with high dilutional growth factors and cytokines. This seems like a promising area. GM-CSF 200C seems to elevate platelets in thrombocytopenic patients, for example. We need NIAID funding for this to go forward. * Carol Brosgart was a principal investigator of the negative CPCRA 023 oral ganciclovir prophylaxis study.

---------------------------------------------------------- We sent surveys to 79 leading AIDS physicians in the U.S., Canada and Europe; 36 (46 percent) responded. We are very grateful to all those who participated in this rather cumbersome open-ended survey:

Donald Abrams, Community Consortium, San Francisco, CA Bernard Bihari, New York, NY Jeff Birnbaum, Kings County Hospital, Brooklyn, NY James Braun, New York, NY Carol Brosgart, East Bay AIDS Center, Berkeley, CA Charles Carpenter, Brown University/Miriam Hospital, Providence, RI Cal Cohen, CRI/New England, Brookline, MA Ann Collier, University of Washington, Seattle, Washington David Cooper, National Centre in HIV, Sydney, Australia Deborah Cotton, Massachusetts General Hospital, Boston, MA Douglas Dieterich, New York University Medical Center, New York, NY Brian Gazzard, Chelsea & Westminster Hospital, London, England Michael Giordano, New York Hospital-Cornell Medical Center, NY, NY W. David Hardy, UCLA School of Medicine, Los Angeles, CA Martin Hirsch, Massachusetts General Hospital, Boston, MA Hans Jäger, Munich, Germany Victoria Johnson, University of Alabama, Birmingham, AL Christine Katlama, HÖpital PitiÄ SalpÄtriÅre, Paris, France Mark Katz, Kaiser Permanente, Los Angeles, CA David Katzenstein, Stanford University Medical Center, Stanford, CA Harold Kessler, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL George Matula, Kaiser Permanente, San Francisco, CA Kenneth Mayer, Memorial Hospital of Rhode Island, Pawtucket, RI Julio Montaner, St. Pauls Hospital, Vancouver, Canada Kenneth Ong, Catholic Medical Center, Jamaica, NY Michael Para, Ohio State ACTU, Columbus, OH Frank Rhame, University of Minnesota, Minneapolis, MN Michael Saag, University of Alabama, Birmingham, AL Joseph Sonnabend, New York, NY Leanna Standish, Bastyr University, Seattle, WA Barbara Starrett, New York, NY Daniel Stein, Albany Medical College, Albany, NY Stephano Vella, Instituto Superiore Di Sanita Paul Volberding, University of California, San Francisco, CA Todd Yancey, New York, NY Mike Youle, St. Stephen's Clinic (Kobler Center), London, England

------------------------------------------------------------- Table 1. As brand names and abbreviations for pharmaceuticals may vary worldwide, the following table lists those used in survey responses.

Generic Name	Brand Name	Abbreviations
------------	----------	-------------
acyclovir	Zovirax	ACV
azithromycin	Zithromax
clarithromycin	Biaxin, Klaricid
delavirdine	Rescriptor
didanosine	Videx	ddI
fluconazole	Diflucan
ganciclovir	Cytovene	DHPG
indinavir	Crixivan
ketoconazole	Nizoral
lamivudine	Epivir	3TC
nevirapine	Viramune
rifabutin	Mycobutin
ritonavir	Norvir
saquinavir	Invirase
stavudine	Zerit	d4T
trimethoprim/	Bactrim, Septra	TMP/SMX
sulfamethoxazole
zalcitabine	Hivid	ddC
zidovudine	Retrovir	AZT, ZDV

Table 2. Regimens Mentioned as First-line Therapy

	Respondents
	# %
AZT/3TC	24 67%
AZT/ddI	12 33%
d4T/3TC	9 25%
ddI monotherapy	7 19%
AZT/ddC	5 14%
ddI/d4T	3 8%
d4T monotherapy	1 3%
d4T/ddC	1 3%
AZT/d4T	1 3%
Reverse trascriptase inhibitors
plus "protease inhibitor"	4 11%
RTIs plus Crixivan	4 11%
RTIs plus Crixivan or Norvir	1 3%

------------------------------------------ Starting Treatment: Examples of Algorithms

Charles Carpenter, Brown University/Miriam Hospital, Providence, RI

I. Initial Therapy

1. Asymptomatic, CD4 350-500

AZT plus ddI or AZT plus 3TC

2. Asymptomatic, CD4 less than 350 or symptomatic at any CD4 count

AZT plus 3TC plus indinavir

II. New Regimen

Begin when patient becomes symptomatic or CD4 drops below pretreatment baseline or when viral load exceeds 10,000 copies/ml.

Michael Para, Ohio State ACTU, Columbus, OH

1. Naive, CD4 greater than 300

AZT plus 3TC or AZT plus ddI (new formulation) or d4T plus 3TC

2. Drug-experienced CD4 greater than 200-300

Depends on what experienced with: change both.

3. CD4 less than 200-300

Drug-naive: AZT plus 3TC plus indinavir (or ritonavir)

Drug-experienced: depends on what experienced with: nucleoside (new or old)+nucleoside (new)+indinavir (or ritonavir)

Mike Youle, St. Stephen's Clinic (Kobler Center), London, U.K. Naive Subjects:

1. At seroconversion: Combo ddI/AZT/protease

2 CD4 greater than 350 Nothing or short-term trial If not a trial, then ddI or ddI plus AZT

3. CD4 200-350 Longer term study If not a trial, start ddI or ddI plus AZT then add 3TC +/- nevirapine or open 3TC then add protease inhibitor

4. CD4 less than 200 Short-term ddI plus AZT then add 3TC plus d4T if no response, add one or more protease inhibitors James Braun, Stacy Kreiswirth, Paul Hergenroeder, New York, NY

---------------------------------------------------------- I. Initial Therapy at Any Stage with Detectable Viral Load:

1. Nucleoside therapy with two drugs AZT/3TC, AZT/ddI, AZT/ddC, d4T/ddI, d4T/3TC

2. Check viral load if less than 300 or undetectable, keep two-drug nucleoside combination if viral load still detectable, add protease inhibitor

a) saquinavir b) indinavir c) ritonavir (The preference for saquinavir is because of the potential cross resistance to saquinavir for patients treated with indinavir. Ritonavir is third choice due to poor patient tolerance. Use ketoconazole 200 mg/day in all saquinavir treated patients.)

II. Experienced patients with an upsurge in viral load with or without a fall in CD4 count with or without occurrence of clinical symptoms/deterioration:

1. Check patient's HIV for genetic resistance to drugs

2. Select two nucleoside analogs based on genotype and tolerance

3. Check viral load in three to five weeks if detectable, add protease inhibitor

a) saquinavir b) indinavir c) ritonavir (If there are not two nucleosides to which the patient is not resistant and can tolerate, than use a single nucleoside, but not AZT, with a protease inhibitor.)

--------------------------------- When to Start Protease Inhibitors

Respondents # %

Critical CD4 Level/Change 12 33% Critical Viral Load Level/Change 12 33% Always as First-Line Therapy 3 8% When Symptoms Appear 3 8% Patient Request 3 8% Never 1 3%

--------------------------- Primary Prophylaxis for OIs Respondents # %

MAC Yes 30 83% No 5 14% Individualized 1 3% Rifabutin First-line 4 18% Macrolide First-line 18 82%

CMV Yes 6 17% No 29 81% Individualized 1 3%

Fungal Yes 4 11% No 31 86% Individualized 1 3%

--------------------------- Preventing PCP Breakthrough

Assuming that PCP prophylaxis was universal, we did not specifically ask about it. However, Dr. Victoria Johnson, University of Alabama, offered an interesting perspective on preventing PCP breakthrough:

I have found that I can reduce episodes of breakthrough PCP with a combination of dapsone 100 mg po daily plus monthly pentamidine, which has reduced hospital admissions for several patients that had recurrent hospitalizations. I find this approach is well tolerated. I am also employing monthly aerosolized pentamidine for patients with memory loss who don't remember to take daily Bactrim.

------------------------- Therapies for Weight Loss Respondents # % Anabolic Steroids 26 72% Nutritional Support 24 67% Megace 15 42% Marinol 12 33% Human Growth Hormone 7 19% Thalidomide 6 17% Total Parenteral Nutrition 4 11% Marijuana 3 8% Other 2 6%

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