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Current Options for First-Line Treatment of HIV Infection

Part II: Case studies

July 2, 2007

Table of Contents

Part I: Strategies for First-Line Therapy

Part II: Case Studies

Case 1. The Apprehensive Teller

Presentation

Marilyn is a 41-year-old woman who was diagnosed in May 2007 with HIV infection after discovering that a previous sexual partner had died of AIDS. She is generally healthy and has no symptoms associated with HIV disease; however, she smokes a pack of cigarettes daily. Currently, the patient is employed as a teller at a bank. She is single, but in a monogamous heterosexual relationship. She was adopted, and therefore does not know her family medical history. She has two healthy teenage children. She does not use recreational drugs. Her laboratory data are listed below in Box 1.

Box 1. Case 1: Baseline Laboratory Data
CD4+ cell count (cells/mm3)297
HIV RNA PCR (copies/mL)34,000
HIV genotype resistance test No resistance detected
Hemoglobin (g/dL) 11.2
Creatinine clearance (mL/min) 61
LDL cholesterol (mg/dL) 122
HDL cholesterol (mg/dL) 33
Triglycerides (mg/dL) 256
Hepatitis C virus Ab Negative
Hepatitis B surface Ab Negative
Hepatitis B surface Ag Negative
Rapid plasma reagin Non-reactive

Physical examination reveals no abnormalities except borderline hypertension, with a systolic pressure of 142 and a diastolic pressure of 88. A pap smear is done and CIN 1 is detected. A purified protein derivative (PPD) is placed and is 0 mm at 48 - 72 hours.

Since her diagnosis, the patient has been anxious and sad. Although she has disclosed her HIV status to her partner, she has not disclosed to her children, other family or friends. In particular, she has expressed that she very much wants to make certain that her elderly mother not discover her HIV status. She is also concerned about being able to afford her HIV medications and care given her income. The patient's employer-provided health insurance plan requires a $20 co-pay on all non-generic medications. Over the past month, the patient has not been sleeping or eating well.

What HIV regimen would you recommend for this patient?

Discussion

Several aspects of this patient's history can inform the selection of HIV therapy. Foremost is addressing this patient's understandable anxiety and sadness since learning she is HIV infected. Individual and group counseling can help her work through the initial phases of dealing with the diagnosis. Further, while the patient's CD4+ cell count indicates she should be started on HIV medications, there is no emergency. The initiation of antiretrovirals can wait until she is mentally better prepared to start treatment that will likely be lifelong.

When both the patient and her clinician feel she is ready to start medications, her preferences regarding dosing frequency and pill counts, as well as concerns regarding potential adverse events, will heavily influence which medications to prescribe.

There is no contraindication regarding using any of the U.S. Department of Health and Human Services (DHHS)-preferred regimens, provided she is not interested in becoming pregnant and is using contraception. If she were interested in becoming pregnant, efavirenz (EFV, Sustiva, Stocrin) should be avoided as it has been determined to be teratogenic in primates. Note, she should be advised to use condoms for birth control, as well as HIV transmission prevention, given potential pharmacological interactions between her HIV therapy and hormonal contraceptives that can render hormonal contraceptives less effective.

Pill Burden

The fixed-dose combination of efavirenz/tenofovir/FTC (EFV/TDF/FTC, Atripla) would be a convenient choice. The fact that her genotype revealed no evidence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance is reassuring. Indeed, the virological results of study A5142 certainly serve to endorse this approach. Further, her apprehension regarding taking medication, as well as her need to cover co-pays, make this a choice that may be reassuring to her.

Adverse Effects

A potential issue with this regimen could be efavirenz-related vestibular disturbance, since the patient is required to be extremely attentive at work. Initiation of this regimen could be delayed until she is due to go on vacation or at least has a long weekend. It's critical to assess patients for their ability to adhere to HIV medications before prescribing treatment. Many clinicians would be hesitant to prescribe NNRTI-based therapies to patients who do not express a strong commitment to take the medications as directed, given worries regarding the development of NNRTI resistance.

Concerns regarding efavirenz-induced fat wasting may be assuaged given that this problem was unusual in patients who were also receiving tenofovir (TDF, Viread), at least in study A5142.

The patient has normal renal function and is not on concomitant nephrotoxic medications, so there is no heightened concern regarding tenofovir administration in this case. However, this patient has hypertension and her creatinine clearance will need to be followed regularly if this regimen is selected.

Other Options

Any one of the preferred boosted-protease inhibitor (PI)-based regimens can also be considered in this case. Were the patient to be leery of the central nervous system (CNS) issues of efavirenz, a boosted-PI regimen would become more preferable. The "resistance to resistance" of these drugs is an attractive feature for clinicians as well as some patients. Lipid levels and abdominal fat can be expected to increase with either a boosted-PI- or an efavirenz-containing regimen and therefore should not be a major consideration.

The convenience of the major boosted PIs would have to be considered. For a patient who is responsible for co-pays, fixed-dose combinations are usually more economical. Any of the boosted PIs could be taken along with tenofovir/emtricitabine (TDF/FTC, Truvada). Clinicians who favor zidovudine/lamivudine (AZT/3TC, Combivir) over tenofovir/emtricitabine would have to justify this choice given its twice-daily dosing. In this patient, her renal function is fine and, if anything, her baseline anemia would steer one away from zidovudine. Though not on the DHHS preferred list, abacavir/lamivudine (ABC/3TC, Epzicom, Kivexa) could be considered an alternative, especially in this patient, who happens to be African American and, therefore, less likely to be genetically predisposed to abacavir hypersensitivity reaction.

Unboosted atazanavir (ATV, Reyataz) -- although not a DHHS preferred PI option -- has to be mentioned given this patient's low high-density lipoprotein (HDL) level, elevated triglycerides and smoking history -- each a factor that increases the risk of cardiovascular disease. Unboosted atazanavir, as opposed to ritonavir (RTV, Norvir)-boosted atazanavir, has been shown in BMS 034 to have no impact on lipids. The drawbacks to unboosted-PI therapy, which have kept such agents off the preferred list, would need to be considered. One could consider making a more substantial modification to this patient's cardiovascular health by controlling her hypertension and helping her to stop smoking. These are issues her clinician should address during subsequent clinic visits.

Decision

After the patient underwent supportive counseling, including a meeting with the clinician and clinic social worker, she was initiated on the fixed-dose combination of efavirenz/tenofovir/FTC. She started the medication on a Wednesday evening and then took off Thursday and Friday from work. Although she reported some vestibular disturbance during the first few days, she noticed improvements in sleep.

At her four-week visit, the patient reported minimal adverse effects and had noted that she had not missed one dose of her medication. Soon thereafter, she was prescribed a generic antihypertensive. Within six months she had also entered a smoking cessation program. Her viral load remains below 50 copies/mL and her CD4+ cell count has exceeded 500 cells/mm3.

Case 2. Advanced AIDS, TB and Treatment Naive

Presentation

Gregory is a 32-year-old man who was recently admitted to the hospital with progressive cough, fever and weight loss of approximately 35 pounds over eight months. He had bilateral pulmonary infiltrates on his chest radiograph and hypoxemia. It was also noted that he had oral thrush and xeroderma.

A comprehensive evaluation during his prolonged hospital stay revealed that he had pulmonary tuberculosis (TB) as well as hepatitis C virus (HCV) infection. An HIV ELISA was reactive and subsequently confirmed. A CD4+ cell count returned at 33 cells/mm3 and his viral load was 125,000 copies/mL (see Box 2 below).

Until six months ago, when he began to get ill, the patient drank alcohol heavily. He also regularly used crack cocaine, although he had not done so in approximately three months (his toxicology screen on admission was negative). He is unemployed. He does not smoke. He is not sexually active.

Box 2. Case 2: Baseline Laboratory Data
CD4+ cell count (cells/mm3) 33
HIV RNA PCR (copies/mL) 125,000
HIV genotype resistance test No resistance detected
Hemoglobin (g/dL) 12.8
Creatinine clearance (mL/min) 68
LDL cholesterol (mg/dL) 78
HDL cholesterol (mg/dL) 24
Triglycerides (mg/dL) 382
Hepatitis C virus Ab Positive
Hepatitis B surface Ab Negative
Hepatitis B surface Ag Negative
Rapid plasma reagin Non-reactive

The patient is prescribed prophylaxis against Pneumocystis jiroveci and Mycobacterium avium. TB treatment with isoniazid (Nydrazid), rifabutin (Mycobutin), ethambutol (Myambutol) and pyrazinamide is also prescribed.

What HIV regimen would you recommend for this patient?

Discussion

All too often, HIV-infected individuals present with advanced HIV disease. In the United States today, the average CD4+ cell count at presentation is approximately 180 cells/mm3.1

In many newly diagnosed patients, opportunistic conditions are evident and are what prompt the patient to seek care. HIV-infected persons are at particularly high risk for pulmonary TB. In fact, worldwide, TB is the most common opportunistic infection for people with AIDS.

In this case, the patient had advanced AIDS, with thrush and wasting syndrome; clearly HIV therapy is indicated. Selection of antiretrovirals for this man, however, is complicated by a number of issues. Foremost, there are important drug-drug interactions between HIV and TB therapies. Rifampin (Rifadin, Rimactane) induces the hepatic metabolism of other drugs, including NNRTIs and PIs, dangerously decreasing their levels. While dose modification of efavirenz -- the least affected NNRTI -- and PIs can be attempted, most clinicians instead opt to use rifabutin, which has less of an induction effect on cytochrome P450 enzymes. Fortunately, there are no major effects of rifampin or rifabutin on nucleoside reverse transcriptase inhibitor (NRTI) concentrations.

A second consideration is the risk of an immune reconstitution syndrome triggered by antiretroviral-mediated improvements in host immunological responses to TB. Such reactions can be severe and some clinicians advocate delaying the initiation of antiretrovirals until the TB has been treated for several months. However, the benefits of this staged approach to TB and HIV therapy have not been well demonstrated. Other clinicians are less hesitant to start HIV treatment early in patients with TB, especially in a patient who is quite advanced in his/her HIV disease.

Lastly, the urgent need for HIV treatment in this case can subsume considerations of this patient's willingness and ability to continually take his therapies and his own preferences regarding therapy.

Decision

In this patient, HIV therapy was prescribed four weeks after the TB treatment commenced. At that time, liver tests did not demonstrate any hepatic adverse reactions to the anti-TB agents, despite the patient's HCV infection. The patient's clinicians decided to treat him with a ritonavir-boosted PI, given concerns about his ability to adhere to HIV therapy and potential drug interactions with other possible regimens. Any of the preferred boosted PIs could be used in this case. The clinicians opted to use the fixed-dose NRTI combination of tenofovir/emtricitabine.

The patient was transferred from the hospital to a skilled nursing facility and eventually was discharged home. His TB medications were administered via directly observed therapy. He was monitored closely for medication toxicity, treatment response and symptoms or signs of immune reconstitution syndrome. His viral load fell to less than 1,000 copies/mL by three months and his CD4+ cell count rose to 125 cells/mm3. He regained much of his lost weight and eventually was driving himself to his clinic appointments.

Please read both the Case Studies and the Strategies for First-Line Therapy sections of this article.

Reference

  1. Egger M. Outcomes of ART in resource-limited and industrialized countries. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Poster 62.


Copyright © 2007 Body Health Resources Corporation. All rights reserved.


Please note: Knowledge about HIV changes rapidly. Note the date of this article, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this article.




This article was provided by TheBodyPRO.com.
 

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