Adapted from

1. NRTI/NtRTI combinations:

a. Tenofovir and emtricitabine

b. Lopinavir/ritonavir (dosed once or twice daily)

c. Atazanavir/ritonavir (dosed once daily)

d. Fosamprenavir/ritonavir (dosed twice daily)

e. Darunavir/ritonavir (dosed once daily)

a. Efavirenz

The decision to choose a NNRTI- or Pi-based regimen as initial therapy is based on many patient- and clinician-specific factors. Drug resistance testing should be performed at diagnosis, and again prior to initiating treatment, if time has elapsed between diagnosis and treatment (see Pharmacologic Treatment for Antiretroviral-Experienced Patients for further discussion of drug resistance testing). The results of resistance testing may dictate which drug class is preferred; 6% to 16% of newly diagnosed patients will have drug-resistant virus. This initial resistance pattern often involves the NNRTIs, but may involve other drug classes. NNRTI-based regimens have low pill burdens and may have decreased incidences of long-term adverse effects (e.g., dyslipidemia) in comparison to some Pi-based regimens. However, this class also has a low threshold for drug resistance (the K103N mutation causes high level cross-class resistance), and patient adherence is a critical consideration. In pregnant women, or women with the potential to become pregnant, a Pi-based regimen is preferred due to the potential teratogenicity of efavirenz (pregnancy category D).

In patients who cannot tolerate the above preferred firstline therapies, or have a compelling reason to choose a different agent, the following alternatives are recommended.

a. Zidovudine and lamivudine b. Didanosine and (emtricitabine or lamivudine)

c. Abacavir and lamivudine

a. Atazanavir (if tenofovir is included in the regimen, ritonavir must be used)

b. Fosamprenavir (dosed twice daily)

c. Fosamprenavir/ritonavir (dosed once daily)

d. Saquinavir/ritonavir

a. Nevirapine in selected populations (due to a more frequent incidence of hepato-toxicity, nevirapine should only be used in patients with low to moderate CD4+ T-cell counts: less than or equal to 250 cells/mm for females, less than or equal to 400 cells/mm for males)

If abacavir is included in a regimen, patients should undergo HLA-B*5701 testing prior to initiation to reduce the risk of abacavir hypersensitivity. Patients who test pos itive for the allele are at high risk (approximately 70%) of developing this reaction, and should not be given abacavir. An abacavir allergy should also be documented in the patient's medical record to prevent future administration. Those patients with a negative test may receive abacavir, but should still be monitored for the development of hypersensitivity.

Therapies not recommended for initial treatment due to poor potency or significant toxicity include triple-NRTI regimens, delavirdine, nevirapine in patients with moderate to high CD4+ T-cell counts, indinavir ± ritonavir, saquinavir used without ritonavir ("unboosted"), ritonavir used without another PI, nelfinavir, tipranvir/ri-tonavir, and tenofovir with didanosine. Due to lack of data in antiretroviral naïve patients, maraviroc, etravirine, enfuvirtide, and raltegravir are not recommended in the DHHS guidelines.

Drugs that should not be combined due to overlapping toxicities include: atazanavir plus indinavir (due to enhanced hyperbilirubinemia), two NNRTIs, and didanosine plus stavudine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when stavudine is combined with zidovudine.

Pharmacologic Therapy for Antiretroviral-Experienced Patients

^ Ongoing viral replication, whether at low levels in the face of adequate drug concentrations or at higher levels due to inconsistent systemic concentrations (or low concentrations in sanctuary sites; e.g., male and female genital fluids, cerebrospinal fluid, or lymph nodes), will eventually lead to resistance to the prescribed medications. There is no consensus on the optimal time to change therapy based on virologie or immunologic failure (Table 87-4). Virologie failure is defined as HIVRNA greater than 400 copies/mL after 24 weeks, greater than 50 copies/mL after 48 weeks, or a repeated HIV RNA greater than 400 copies/mL after prior suppression to less than 400 copies/mL.5 Some clinicians may change therapy with any repeated, detectable viremia (HIV RNA greater than 50-400 copies/mL), while others will set arbitrary thresholds of 1,000 to 1,500 copies/mL. Immunologic failure is defined as having an increase of less than 25 to 50 cells/mm in CD4+ T lymphocyte count above baseline after 1 year of therapy, or a decline in CD4+ cell count below baseline while taking antiretroviral therapy.

Treatment considerations for antiretroviral-experienced patients are much more complex than for patients who are naïve to therapy. Prior to changing therapy, the reasons for treatment failure should be identified. A comprehensive review of the patient's severity of disease, antiretroviral treatment history, adherence to therapy, intolerance or toxicity, concomitant drug therapies, comorbidities, and results of current and past HIV resistance testing should be performed. If patients fail therapy due to poor adherence, the underlying reasons must be determined and addressed prior to initiation of new therapy. Reasons for poor adherence include: problems with medication access, active substance abuse, depression and/or denial of the disease, and a lack of education on the importance of 100% adherence to therapy. Medication intolerance or toxicity can be remedied with therapy for the adverse event, exchanging the drug causing the toxicity with another in the same class, or changing the entire regimen. Pharmacokinetics or systemic drug exposure can be optimized by ensuring maximal drug absorption (taking the drug with or without food can alter exposure by up to 30%), and avoiding interactions with concomitant prescription or nonprescription medications and dietary supplements or natural products (e.g., antacids, St. John's wort, and garlic). When causes for treatment failure are identified, appropriate strategies for therapy can be determined.

Table 87-4 Treatment Options Following Virologie Failure With the Initial Regimen Initial Regimen

Initial Regimen_Recommended Change

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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