Advertisement
The Body: The Complete HIV/AIDS Resource
Follow Us Follow Us on Facebook Follow Us on Twitter Download Our App
Professionals >> Visit The Body PROThe Body en Espanol
Read Now: Expert Opinions on HIV Cure Research
  
  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

Pull Out and Save

Optimal Antiretroviral Therapy for HIV Infection

Updated Recommendations of the International AIDS Society - U.S.A.

Decmber 1997

Only traditional clinical trials can tell us if a new drug is safe and effective when used as long-term antiretroviral therapy, and only head-to-head comparative studies can determine if one antiretroviral agent, or combination of agents, is better than another. Without the data from large-scale, long-running, randomized, double-blind, well-controlled clinical trials, our approach to the treatment of patients with HIV infection would be based on little more than anecdotal information, clinical experience, educated guesswork, and good intentions.

Clinical trials are the foundation upon which all recommendations regarding therapy are based. They are indispensable to the process of formulating guidelines for treatment. They are also enormously expensive and time-consuming. The development of a new antiretroviral agent -- even one that benefits from the accelerated approval process instituted by the F.D.A. several years ago -- can cost tens or even hundreds of millions of dollars, and the testing of that agent, in Phase I, II, and III clinical trials, can take four to six years.

People with HIV disease -- especially those with advanced disease who have developed high-level resistance to one or more of the F.D.A.-approved antiretroviral agents -- cannot wait years for a promising new drug to be made available. Many of them cannot wait months. They have exhausted their therapeutic options, and they need access to experimental agents now, before unchecked viremia overwhelms them.

The F.D.A. has responded to the urgency of this situation by establishing a "fast-track" approval process for drugs that show particular promise in early clinical trials. Antiretroviral drugs have been the principal beneficiaries of this streamlined process -- and that is altogether appropriate, given that AIDS patients and their advocates were instrumental in persuading the F.D.A. to institute this accelerated approval process.

Advertisement
The pharmaceutical industry, for its part, has responded to this situation by setting up "compassionate-release" and "expanded-access" programs to make promising new drugs available to patients who have failed standard therapies before those new drugs win F.D.A. approval. We regularly alert readers to the existence of these special programs, and we provide practitioners with 800 numbers they can call to obtain further information or to enroll patients (see, for example, "Newest protease inhibitor, nelfinavir, is first available in pediatric formulation," Vol. 3, No. 1, pages 18-19, and "Oral suspension of itraconazole is available through a compassionate-release program," page 23 of the same issue).

All of us who treat patients with HIV disease have confronted this situation, which has become more commonplace as HIV-infected individuals live longer -- and yet fail to sustain maximal viral suppression with particular combinations of antiretroviral agents. Many patients will "break through" on treatment because of extensive prior antiretroviral therapy, because they have very advanced HIV disease, or because of problems with adherence to these complex multidrug regimens.

With the possibility of drug breakthroughs in mind, we must now think in terms of subsequent antiretroviral strategies. While it seems unwise to select an initial treatment based on the possibility of therapeutic failure, this clinical reality is being discussed by many clinicians who treat people with HIV infection.

There are no hard-and-fast guidelines for how to treat HIV-positive patients after they develop resistance to one or more antiretroviral agents -- which is why it is so important to consider the full range of treatment options before therapy is initiated. The best antiretroviral effects are achieved with the initial therapy; subsequent treatments have significantly smaller, and less durable, effects.

The members of the I.A.S. - U.S.A. advisory panel recognize that increasing numbers of patients fall into the shadowy area where treatment decisions based on the hard data from clinical trials end and treatment decisions based on anecdotal information, clinical experience, educated guesswork, and good intentions begin. To assist practitioners in making these difficult decisions, the panel has not confined itself to making recommendations about initial antiretroviral regimens but has offered concrete suggestions for changing antiretroviral therapy in patients who have failed their initial regimen.

These revised treatment guidelines are based on the clinical data available to the committee as of mid-1997. All of us involved in drafting these treatment recommendations recognize that the field of HIV therapy is an extremely dynamic one, and it is our expectation that these guidelines will require further revision next year. Among other things, half a dozen new antiretroviral agents will soon be made available to clinicians who treat HIV infection (see "The Next Generation of Antiretroviral Agents -- An Update," in this issue). These new drugs will be used first in patients who have exhausted other therapeutic options, but in time many of them will become standard therapy -- perhaps even first-line therapy -- for HIV infection.


Rationale for the updated recommendations

With all of these considerations and caveats in mind, my colleagues at the International AIDS Society - U.S.A. have developed a revised set of guidelines for optimal antiretroviral therapy in patients infected with HIV. (These recommendations supersede the guidelines issued by the I.A.S. - U.S.A. in July of 1996.) The panel's guidelines reflect an enhanced understanding of HIV pathogenesis itself. What was once thought to be a process characterized by a long dormant period is now recognized to be characterized by a high rate of viral turnover -- estimated to exceed 10 billion HIV particles per day, even during the asymptomatic phase of infection.

This intense, incessant viral activity within the lymphoid tissue of the body ultimately destroys key parts of the lymph system. There is now evidence that the amount of HIV expressed in lymphoid tissue may be higher and more intense than plasma concentrations would suggest -- meaning that even moderate levels of plasma HIV RNA may reflect high-level viral replication in these tissues.

"There is a continuum of risk over the entire range of measurable HIV RNA levels -- and there seems to be no lower limit of risk. We know, for example, that disease progression does occur even in patients with plasma HIV RNA levels below 5,000 copies/mL."

The laboratory tool that has contributed most to our understanding of HIV pathogenesis -- and of the efficacy of various antiretroviral regimens -- is the HIV RNA quantitation assay (see "The HIV RNA Assay: A Valuable New Clinical Tool," Vol. 2, No. 2). In both natural-history studies and controlled clinical trials, the level of HIV RNA in a patient's plasma has been shown to be the most powerful predictor of disease progression and clinical outcome. There is a continuum of risk over the entire range of measurable HIV RNA levels -- and there seems to be no lower limit of risk. We know, for example, that even in patients with plasma HIV RNA levels below 5,000 copies/mL disease progression does occur, at a measurable, albeit very low, rate.

Moreover, data presented at a major scientific symposium in Toronto earlier this fall indicate that HIV is present even in patients whose HIV RNA levels have remained below the detection limits of the currently available assays for extended periods of time, and this finding suggests that it may never be possible to fully eradicate HIV, once an individual has been infected (see "HIV found in the lymph tissue of patients with 'undetectable' viral levels," in the Newsline section of this issue).

On the plus side, therapy-induced declines in plasma HIV RNA levels are strongly associated with a decreased risk of disease progression, and physicians and patients alike should focus on what can be achieved with combination antiretroviral therapy that suppresses viral replication below detectable levels. In adherent patients, these potent regimens dramatically retard disease progression, reduce the incidence of opportunistic infections and hospitalizations, and forestall serious illness and death.


When should you initiate therapy?

Taken together, the data presented above provide a scientific rationale for more aggressive treatment of HIV infection. The I.A.S. - U.S.A. advisory panel has long recommended treatment for all individuals with symptomatic disease, those with CD4 counts below 500 cells/mm3, and those with plasma HIV RNA concentrations above the range of 30,000 to 50,000 copies/mL. The panel also recommended that therapy be considered for individuals with HIV RNA levels greater than 5,000 to 10,000 copies/mL.

Therapy is now recommended for all patients with plasma HIV RNA concentrations greater than 5,000 to 10,000 copies/mL, irrespective of the patient's CD4 cell count (Table 1).


Table 1: Considerations for Initiating Antiretroviral Therapy

  • Therapy is recommended for all patients with HIV RNA levels above 5,000 to 10,000 copies/mL of plasma

  • Therapy should be considered for all HIV-infected patients with detectable HIV RNA

  • For patients at low risk of progression (low plasma HIV RNA level and high CD4 count), particularly those who are not committed to complex antiretroviral regimens, therapy may be deferred. These patients should be reëvalulated every 3 to 6 months


Because there is considerable variability among the different HIV RNA assays -- and among different generations of the same assay -- it is important to use the same assay, whatever it may be, for each successive measurement of viral load in each patient. This variability also makes it impossible to designate an absolute threshold for the initiation of therapy. Instead, the panel has designated a range of HIV RNA levels and left the final decision to the clinician on a case-by-case basis.

Therapy should be considered for all patients with detectable plasma HIV RNA who request treatment and who are committed to lifelong adherence to treatment. In patients with low plasma HIV RNA levels and high CD4 cell counts, therapy may be safely deferred in the short term, but viral load should be reëvaluated every three to six months. In situations in which HIV RNA assays are not available, the panel recommends that therapy be initiated in all individuals with CD4 counts below 500 cells/mm3, even if they have no overt symptoms of HIV disease.


Initial antiretroviral regimens

The preferred initial regimen, in the panel's estimation, is the one most likely to suppress viral replication below the level of detection of most of the currently available HIV RNA assays -- that is, below 400 to 500 copies/mL. In theory, it is the potency of the regimen, not the number of drugs per se, that is important. In practice, this translates into a three-drug regimen that includes two nucleoside analogs and a protease inhibitor with strong in vivo potency (Table 2).


Table 2: Selected Options for Initiating Therapy*†
REGIMEN‡§
ADVANTAGES
DISADVANTAGES
NRTI-1 and
NRTI-2 and PI
This regimen should be able to achieve plasma HIV RNA levels below limit of detection in a large majority of drug-adherent patients Strict adherence to this regimen is crucial; quality of life may be affected; durability of effect, long-term tolerance, and overall clinical benefit in antiretroviral-naïve patients with early disease not fully defined
NRTI-1 and
NRTI-2 and
NNRTI
Many patients taking this regimen achieve plasma HIV RNA levels below limit of detection; it also permits deferral of a PI if this option is chosen Strict adherence to this regimen is crucial; may not be as potent as a PI-containing regimen; it is not recommended for patients with advanced disease (i.e., low CD4 counts or high plasma viral load); durability of effect and overall clinical benefit not fully defined


* NRTI indicates nucleoside analog reverse-transcriptase inhibitor; PI, protease inhibitor; HIV, human immunodeficiency virus; and NNRTI, non-nucleoside reverse-transcriptase inhibitor. Numerals 1 and 2 indicate different entities in a class of drugs.

† Potent regimens, exemplified by currently available 3-drug combinations, are listed. Careful consultation with the patient to discuss the need for long-term committment to a complex regimen is essential before initiating triple-drug therapy. Double-NRTI combinations have a role in defined circumstances (see text). Other combinations (eg, double-protease inhibitor regimens) are under study.

‡ Acceptable combinations of 2 NRTIs include either zidovudine combined with lamivudine, didanosine, or zalcitabine, or stavudine combined with lamivudine or didanosine. Protease inhibitors with potent in vivo activity are recommended; currently these include indinavir, ritonavir, and nelfinavir.

§ Of the currently approved NNRTIs, nevirapine and delavirdine, data are only available for the effectiveness of nevirapine for this application.


Before therapy is initiated, the clinician needs to have a detailed discussion with each patient, to assess the patient's ability -- and willingness -- to commit to compliance with these complex, costly, and potentially toxic regimens.

This assessment is particularly important in asymptomatic patients in the early stages of HIV disease, as the ability to maintain long-term adherence to multidrug antiretroviral regimens is a major challenge -- and faltering adherence can promote the emergence of drug-resistant viral strains. Given the potential for cross-resistance among the protease inhibitors (see "Protease Inhibitor Resistance and Salvage Therapy," in this issue), a patient's treatment options can be profoundly compromised by anything short of full compliance.

Although a three-drug regimen that contains a protease inhibitor is the preferred initial regimen because of its potency, it is not the ideal initial regimen for all patients. Some cannot tolerate the side effects of protease inhibitor therapy; others cannot conform to the demands of the dosing schedules, or the dietary restrictions, or the rehydration requirements; and still others cannot afford the drugs. For these patients the recommended alternative is a regimen that combines two nucleoside analogs and a non-nucleoside reverse-transcriptase inhibitor.

There have been few direct comparisons of protease inhibitor- and NNRTI-containing three-drug regimens, but the evidence we do have suggests that the extent and duration of viral suppression is greater with combinations that contain a potent protease inhibitor. However, the INCAS trial has established an important principle in the use of NNRTIs -- namely that their effectiveness is maximized when they are used in combination with nucleoside analogs to which the patient has had no prior exposure. Moreover, the INCAS results are consistent with the thesis that near-complete suppression of viral replication can prevent the early emergence of drug resistance.

To date, the data on regimens that contain two protease inhibitors -- and those than combine a nucleoside analog, an NNRTI, and a protease inhibitor -- are insufficient to tell us what role these combinations may eventually play in initial therapy. The pairing of saquinavir and ritonavir shows promise, with a high proportion of patients achieving undetectable HIV RNA levels after 20 weeks of therapy, and it is reasonable to expect that these results will improve as increasing numbers of patients are switched over to the new soft-gel formulation of saquinavir, which has roughly nine times the bioavailability of the old formulation. Preliminary data are being gathered on other regimens that contain two protease inhibitors, but as yet these findings are too fragmentary to serve as the basis for a recommendation that they be used as initial therapy.

Patients who are not considered candidates for triple-drug therapy, but who are considered at high risk for disease progression, should be started on a regimen that contains two nucleoside analogs. Two of these two-drug regimens -- d4T plus ddI and d4T plus 3TC -- have been demonstrated to produce reductions in viral load of approximately 1.5 log in antiretroviral-naïve patients, and they offer the convenience of twice-daily dosing. The combinations of ZDV plus ddI, ZDV plus ddC, and ZDV plus 3TC have also been shown to confer clinical benefit.

All five of these two-drug combinations may be used as stand-alone therapies, although they are more appropriately -- and more effectively -- combined with either a protease inhibitor or an NNRTI. At the present time, monotherapy with any of the currently available antiretroviral agents is not recommended as initial therapy. At best, monotherapy results in transient reductions in viral load; at worst, it compromises future therapy by selecting for viral mutants that are resistant to one or more antiretroviral agents. Moreover, certain two-drug regimens -- specifically ddC plus ddI, ddC plus d4T, ddC plus 3TC, and ZDV plus d4T -- are not recommended because of the limited efficacy of these combination therapies.


When should you change antiretroviral therapy?

A patient's therapeutic regimen should be changed for any of the following reasons: treatment failure (as measured by rising viral load and/or falling CD4 counts), toxic side effects or intolerance of therapy, or poor adherence (as reported by the patient or perceived by that patient's primary care-providers). Therapy should also be changed if the patient is on an outmoded or suboptimal regimen (Table 3).


Table 3: Indications for Changing Therapy

  • Treatment failure, as suggested by a confirmed rising plasma HIV RNA level or failure to achieve the desired reduction in plasma viral load; declining CD4 cell count; or clinical disease progression

  • Unacceptable toxicity of, intolerance of, or nonadherence to the regimen

  • Current use of suboptimal treatment regimens, i.e., antiretroviral monotherapy


While there are, as yet, no data from controlled clinical trials to establish precise criteria for treatment failure, the definition of treatment failure has been refined to reflect the availability of a number of potent regimens, the strong scientific rationale for strict control of viral replication, and the realization that drug-resistant viral mutants emerge whenever there is ongoing viral replication.

As a general guideline, patients who have achieved levels of plasma HIV RNA that are below detectable limits -- particularly those who are taking a protease inhibitor-containing regimen -- should have their therapy switched if successive HIV RNA assays confirm that their viral load is increasing. Ideally, any confirmed detectable HIV RNA level is an indication that therapy should be changed, but from a practical standpoint, given the limited number of therapeutic alternatives available to patients who break through on their initial antiretroviral therapy, it may be reasonable to wait until the documented increase in plasma HIV RNA reaches the level of from 2,000 to 5,000 copies/mL before changing therapies. This recommendation also applies to patients taking regimens that consist of two nucleoside analogs.

The unanswered question, at this point, is whether patients who achieve undetectable levels of HIV RNA on their assigned therapy should have another antiretroviral agent added to their regimen. This approach, which has been termed "treatment intensification," is under study, but it is premature to make any recommendations concerning the advantages of such an approach.

For patients who achieve a significant initial decrease in plasma HIV RNA levels but whose viral load never falls below detection limits, a confirmed increase in HIV RNA to a level greater than 5,000 to 10,000 copies/mL should dictate a treatment change. Because factors other than viral resistance -- such as poor adherence, recent vaccinations, and intercurrent illnesses -- can affect viral suppression, all patients should be carefully evaluated before any change in therapy.

One must be especially careful not to abandon a given regimen too soon after it is initiated, as it can take 12 to 24 weeks for the full effects of a multidrug antiretroviral regimen to be felt after the initial drop in HIV RNA levels. This is especially true for patients who achieve a substantial initial reduction in plasma HIV RNA, on the order of 1.5 to 2.0 logs, but whose viral load does not drop below the level of detection. Abandonment of such a patient's regimen is not necessarily indicated; an alternative approach is to continue therapy, with close observation until there is a confirmed and substantial rise in viral load above the maximal reduction achieved.

Other indications of treatment failure are: lack of initial virological response, return to pretreatment HIV RNA levels, declining CD4 counts, and clinical evidence of disease progression. Complicating this definition somewhat is a phenomenon increasingly reported in patients taking protease inhibitor-containing regimens -- a discordance between HIV RNA levels and CD4 counts. This discordance, which may develop after several weeks or several months of therapy, occurs when HIV RNA levels return to pretreatment levels even though CD4 counts remain substantially above pretreatment levels.

Although the pathophysiological basis for this phenomenon is not clear, we do know that HIV replication is the driving force in disease progression -- and therefore the panel recommends that therapy be changed for patients who present with discordance, so long as an alternative therapy exists. The converse of this situation can also occur -- CD4 counts can decline progressively even after HIV RNA levels have fallen to undetectable levels. Here, too, many experts recommend changing therapy, especially if the CD4 count drops rapidly.


How should you handle therapy-limiting toxicity?

When toxic effects of therapy necessitate the modification or discontinuation of treatment, dose reductions of the protease inhibitor component should be avoided if at all possible. If the toxic effect is due to a nucleoside analog (e.g. pancreatitis related to ddI therapy), the offending agent should be replaced with one that has a different toxicity profile. If the basis for the toxic effect is unclear, brief and complete interruption of the full therapeutic regimen is recommended.

Once the toxic event has resolved, the clinician must use his best judgment, based in part on the alternative therapies available to the patient in question, to determine whether to replace only the offending drug in the initial regimen or all three drugs.


What to change to

In all cases of treatment failure, the guiding principle is to change all the drugs in the failed regimen or, barring that, at least two of the three drugs. The practice of adding a single drug, or substituting a single drug, to an insufficiently suppressive regimen is strongly discouraged. This approach is, in effect, sequential monotherapy -- and it leads to more rapid emergence of drug-resistant viral strains.

The panel has proposed a number of alternative combination therapies for patients who fail their initial three-drug regimen (Table 4). They have also provided therapeutic options for patients deemed to be failing two-nucleoside regimens (Table 5). Although a number of four-drug regimens are currently in early clinical trials, it is not yet known whether the benefits of such regimens will justify the predictable increase in toxic effects, in adherence problems, and in cost.


Table 4: Examples of Alternative Antiretroviral Regimens for Treatment Failure on Three-Drug Regimens*†
INITIAL REGIMEN
ALTERNATIVE COMBINATIONS
Zidovudine-lamivudine-protease inhibitor-1 Stavudine-didanosine-protease inhibitor-2 ‡
Stavudine-didanosine-NNRTI §
Ritonavir-saquinavir-NRTI ||
Stavudine-lamivudine-protease inhibitor-1 Zidovudine-didanosine-protease inhibitor-2 ‡
Zidovudine-didanosine-NNRTI §
Ritonavir-saquinavir-NRTI ||
Zidovudine-didanosine-protease inhibitor-1 Stavudine-lamivudine-protease inhibitor-2 ‡
Stavudine-lamivudine-NNRTI §
Ritonavir-saquinavir-NRTI ||
Stavudine-didanosine-protease inhibitor-1 Zidovudine-lamivudine-protease inhibitor-2 ‡
Zidovudine-lamivudine-NNRTI §
Ritonavir-saquinavir-NRTI ||
Zidovudine-didanosine-NNRTI Stavudine-lamivudine-protease inhibitor-1
Zidovudine-lamivudine-protease inhibitor-1


* NRTI indicates nucleoside analog reverse-transcriptase inhibitor; NNRTI, non-nucleoside reverse-transcriptase inhibitor; and PI, protease inhibitor. Numerals 1 and 2 indicate different entities in a class of drugs.

† Regimens listed are examples of potential alternatives for initial regimens listed in Table 1 and are not meant to be all-inclusive. The principle of switching 2 or 3 new drugs is indicated when failure on the initial regimen has occurred. In practice, options are limited beyond the first alternative, and a component of prior regimen may need to be continued or recycled after failure of a second or third regimen. The NRTI-NNRTI-PI regimens are under study, but pharmacokinetic interaction and safety data are not available.

‡ The best alternative PI after failure on initial PI-containing regimen is unknown. Cross-resistance between indinavir and ritonavir is nearly complete. Thus, virological failure (as opposed to intolerance) of one may severely limit the use of the other. Indinavir or ritonavir may or may not select for cross-resistance to nelfinavir.

§ The use of a currently available NNRTI is unlikely to result in suppression of plasma HIV RNA below detection levels in antiretroviral-experienced patients.

|| Efficacy of ritonavir and saquinavir and 1 or more NRTI in combination in this circumstance is unclear and is under study.


Table 5: Examples of Alternative Antiretroviral Regimens for Treatment Failure on a Double-NRTI Combination*†
INITIAL REGIMEN
ALTERNATIVE COMBINATIONS
Zidovudine-didanosine Zidovudine-lamivudine-protease inhibitor ‡
Stavudine-lamivudine-protease inhibitor ‡§
Ritonavir-saquinavir-NRTI ||
Zidovudine-zalcitabine Zidovudine-lamivudine-protease inhibitor ‡
Stavudine-lamivudine-protease inhibitor ‡§
Stavudine-didanosine-protease inhibitor ‡§
Ritonavir-saquinavir-NRTI ||
Zidovudine-lamivudine Stavudine-didanosine-protease inhibitor ‡§
Ritonavir-saquinavir-NRTI § ||
Stavudine-didanosine Zidovudine-lamivudine-protease inhibitor ‡
Ritonavir-saquinavir-NRTI ||
Stavudine-lamivudine Zidovudine-didanosine-protease inhibitor ‡
Ritonavir-saquinavir-NRTI § ||


* NRTI indicates nucleoside analog reverse-transcriptase inhibitor; PI, protease inhibitor; and NNRTI, non-nucleoside reverse-transcriptase inhibitor.

† Regimens listed are examples of potential alternative combinations and are not meant to be all-inclusive. The principle of switching 2 or 3 new drugs is indicated when failure on an initial, double-NRTI regimen has occurred. Regimens containing an NNRTI plus a PI are under development and should be used only when full pharmocokinetic interaction and safety data are available.

‡ Protease inhibitors with potent in vivo activity are recommended; currently these include indinavir, ritonavir, and nelfinavir.

§ If the patient or physician wishes to defer PI use, an NNRTI could be substituted, but suppression of plasma HIV RNA below the level of detectability with NNRTIs has not yet been documented in patients with prior antiretroviral experience.

|| Optimum strategic use of double-PI combinations (e.g., ritonavir and saquinavir with 1 or more NRTI) is unclear. Whether it is preferable to employ them in this circumstance or after failure on a single PI has not been determined. Other double-PI combinations are under study.


"If the sheer complexity of the dosing regimen -- or any of a number of other, psychosocial factors -- is the root cause of a patient's non-compliance, then a simpler regimen may be more appropriate and, in the long run, more effective -- even if that regimen is less potent than its predecessor."

When therapy is changed because of poor adherence (and the linked concern that non-compliance will lead to increased viral resistance), it is important to explore the reasons for the patient's poor adherence to therapy. If the non-compliance is attributable to low-grade toxic effects, then changing the offending component of the regimen may rectify the problem.

If, on the other hand, the sheer complexity of the dosing regimen -- or any of a number of other, psychosocial factors -- is the root cause of the patient's non-compliance, then a simpler regimen may be more appropriate and, in the long run, more effective -- even if that regimen is less potent than its predecessor.


Conclusion

Recent data have provided strong support for the principle that viral replication should be suppressed as fully as possible throughout the course of HIV infection. The field of antiretroviral therapy is a dynamic and rapidly evolving one, and the editors of HIV Newsline anticipate that it will be necessary to update this material within the year.


For Further Information

To obtain reprints of the full text of the International AIDS Society - U.S.A. recommendations for antiretroviral therapy, write to I.A.S. - U.S.A. at 353 Kearny Street, San Francisco, CA 94108.

Paul A. Volberding, M.D., is Editor-in-Chief of HIV Newsline and AIDS Program Director at San Francisco General Hospital.





  
  • Email Email
  • Printable Single-Page Print-Friendly
  • Glossary Glossary

This article was provided by San Francisco General Hospital. It is a part of the publication HIV Newsline.
 

Tools
 

Advertisement