HIV AIDS medical therapy
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The primary goal of antiretroviral therapy (ART) is to reduce HIV-associated morbidity and mortality. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of plasma HIV RNA (viral load) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease.. Major classes of agents used in the treatment of HIV are: Non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists, and integrase inhibitors. All regimens are combinations of at least 3 agents, preferably with 2 NRTIs. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated inflammation and its associated complications.
Anti-HIV medications (also called antiretrovirals) are grouped into six drug classes according to their mechanism of action. The six classes are as follows:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- Nucleoside reverse transcriptase inhibitors (NRTIs).
- Protease inhibitors (PIs).
- Fusion inhibitors.
- CCR5 antagonists.
- Integrase inhibitors.
Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. 
Goals of Therapy
- Durable suppression of HIV viral load ( to <50 cells/mL ).
- Restoration of normal CD4 cell count.
- Prevention of transmission of the disease.
- Prevention of building of drug resistance.
- Improvement in quality of life of the patient.
- Current optimal HAART options consist of drug combinations consisting of at least three drugs belonging to at least two classes of antiretroviral agents.
- Typical regimens consist of:
- Two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) PLUS
- Either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
- In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.
WHO Recommendations in Adults
▸ Click on the following categories to expand treatment regimens.
National Institute of Health (NIH) Recommendations
▸ Click on the following categories to expand treatment regimens.
|Drug Name||Dose||Adverse Events|
|Nucleoside Reverse Transcriptase Inhibitors (NRTIs)|
||300 mg BID or 600 mg once daily||Fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise, fatigue, sore throat, cough, shortness of breath.|
||400 mg once daily
In combination with TDF: 200 mg once daily
|Pancreatitis, nausea, vomiting, peripheral neuropathy, retinal changes, optic neuritis, lactic acidosis with hepatic steatosis.|
||200 mg once daily||Hyperpigmentation, skin discoloration|
||250-300 mg BID||Macrocytic anemia, neutropenia, nausea, vomiting, headache, insomnia, asthenia, nail pigmentation, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, lipoatrophy, myopathy.|
||150 mg BID or 300 mg once daily||Minimal toxicity, severe acute exacerbation of hepatitis may occur in HBV coinfected patients who discontinue 3TC.|
|| >60 kg: 40 mg BID
<60 kg: 250 mg BID
|Peripheral neuropathy, lipoatrophy, pancreatitis, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, rapidly progressive ascending neuromuscular weakness (rare).|
|300 mg once daily||Renal insufficiency, Fanconi syndrome, osteomalacia, decrease in bone mineral density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients who discontinue TDF, asthenia, headache, diarrhea, nausea, vomiting, and flatulence.|
|Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)|
||600 mg once daily||Rash, increased transaminase levels, hyperlipidemia, dizziness, somnolence, insomnia, depression, suicidality, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria|
||200 mg BID||Rash, Stevens-Johnson syndrome, nausea|
||200 mg once daily for 14 days, then 200 mg BID or 400 mg once daily||Rash, Stevens-Johnson syndrome, nausea, hepatitis|
||25 mg once daily||Rash, depression, insomnia, headache, hepatotoxicity|
|Protease Inhibitors (PIs)|
|| 400 mg once daily
In combination with TDF: 300 mg + RTV 100 mg once daily
In combination with EFV: 400 mg + RTV 100 mg once daily
|Indirect hyperbilirubinemia, PR interval prolongation, hyperglycemia, fat maldistribution, cholelithiasis, nephrolithiasis, renal insufficiency, increase in transaminase levels, hyperlipidemia, skin rash|
||800 mg once daily||Skin rash, Stevens-Johnson syndrome, hepatotoxicity, diarrhea, nausea, headache, hyperlipidemia, fat maldistribution, hyperglycemia.|
|| 1400 mg BID or
700 mg + RTV 100 mg BID
In combination with EFV: 700 mg + RTV 100 mg BID or 1400 mg + RTV 300 mg once daily
|Skin rash, diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, increase in transaminase levels, nephrolithiasis, fat maldistribution.|
||800 mg q8h||Nephrolithiasis, nausea, hepatitis, indirect hyperbilirubinemia, hyperlipidemia, headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia, hyperglycemia, fat maldistribution.|
||400 mg/100 mg BID or 800 mg/200 mg once daily||Diarrhea, nausea, vomiting, pancreatitis, asthenia, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels, PR interval prolongation, insulin resistance/diabetes mellitus.|
||1250 md BID or 750 mg TID||Diarrhea, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels.|
||100-400 mg/d q12-24h||Diarrhea, nausea, vomiting, paresthesia, hyperlipidemia, hepatitis, asthenia, taste perversion, hyperglycemia, fat maldistribution.|
||1000 mg BID||Diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, fat maldistribution, PR interval prolongation, insulin resistance/diabetes mellitus.|
||500 mg BID||Hepatotoxicity, skin rash, hyperlipidemia, hyperglycemia, fat maldistribution.|
||50 mg q12-24h||Rash, insomnia, headache.|
||150 mg once daily||Nausea, diarrhea, decrease bone density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients.|
||400 mg BID||Rash, Steven-Johnson syndrome, toxic epidermal necrolysis, nausea, headache, diarrhea, pyrexia, CPK elevation.|
||90 mg SQ BID||Local injection reactions, increased incidence of bacterial pneumonia, rash, fever, nausea.|
||150-600 mg BID||Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity.|
|Strength of recommendation||Level of evidence|
|A. Strong||I. One or more randomized trials with clinical outcomes and/or validated laboratory endpoint|
|B. Moderate||II. One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes|
|C. Optional||III. Expert opinion based on evaluation of other evidence|
- Antiretroviral therapy (ART) is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:
- CD4 count <350 cells/mm3 (AI)
- CD4 count 350 to 500 cells/mm3 (AII)
- CD4 count >500 cells/mm3 (BIII)
- Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
- Effective ART also has been shown to prevent transmission of HIV from an infected individual to a sexual partner; therefore, ART should be offered to patients who are at risk of transmitting HIV to sexual partners (AI [heterosexuals] or AIII [other transmission risk groups].
- Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case by case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.
|Definitions of Treatment Failure|
|CD4 Cell Failure||
|Table adapted from WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection|
|Treatment Failure Criteria||Stage 1||Stage 2||Stage 3||Stage 4|
|CD4 cell failure||Not recommended to switch regimen. Repeat CD4 count in 3 months||Not recommended to switch regimen. Repeat CD4 count in 3 months||Consider switching to second-line regimen†||Recommend to switch to second-line regimen†|
|CD4 cell failure and viral load failure||Consider second-line regimen†||Consider second-line regimen†||Recommended to switch to second-line regimen†||Recommended to switch to second-line regimen†|
| † Switching should not be done until the first regimen has been given sufficient time to succeed (at least 6 months). |
Table adapted from WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS 
- HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.
- It would take more than the lifetime of an individual to be cleared of HIV infection using HAART.
- Many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.
HIV in Children
Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.
Adherence is taking the correct dose of each anti-HIV medication at the correct time and exactly as prescribed. Adherence is very important for successful HIV treatment. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues, along with side effects that create intentional non-adherence, also has a weighty impact.
Difficulty in Adherence
There are several reasons why adhering to an HIV treatment regimen can be diicult. Most treatment regimens involve taking several pills every day with or without food, or before or after other medications. Other factors that can make treatment adherence difficult include:
- Difficulty taking medications (such as trouble swallowing pills).
- Side effects from medications (for example, fatigue or diarrhea).
- Daily schedule issues (including a busy schedule, shift work, or travel away from home) .
- Being sick or depressed .
- Alcohol or drug abuse.
Importance of Adherence
Adherence effects the success of HIV treatment in two ways:
- Good adherence to an HIV treatment regimen helps anti-HIV medications work effectively to reduce the viral load. Skipping medications, even occasionally, gives HIV to multiply rapidly. Preventing the virus from multiplying is the best way to stay healthy.
- Good adherence to an HIV treatment regimen also helps prevent drug resistance. One or more anti-HIV medications in a treatment regimen can become ineffective as a result of drug resistance.
Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
The most reliable indicator of response to ART is plasma HIV RNA and should be measured in all patients at baseline and regularly during therapy. It is thus useful in predicting clinical progression.
Viral load reduction may be more rapid in following patients:
- Having high CD4 cell count.
- Having lower levels of baseline viremia.
- In treatment-naive patients.
|Time||Expected decrease in Viral load|
|1 week||Decrease by 0.75 to 1 log10 copies/mL|
|1 month||Decrease by 1.5 to 2 log10 copies/mL to <5000 copies/mL .|
|2 to 4 months.||<500 copies/mL|
|4 to 6 months.||< 50 copies/mL.|
Transient increase in the viral load can be present in acute illness and vaccinations.
It is defined either as primary failure to achieve a viral load <50 copies/mL or any sustained recurrence of viremia to >50 copies/mL after initial viral suppression.
Two main causes of the failure are:
- Drug resistance.
- Failure of the drugs to reach the target site.
Department of Health and Human Services (DHHS) have suggested that viral blips do not require intervention with a new regimen unless the viral load is sustained at >200 copies/mL.
Monitoring CD4 and Viral Load
|Scenario||CD4 Monitoring||Viral Load Monitoring|
|Before receiving ART||Yes||Yes|
|While receiving ART||3 month after initiation of ART||2-4 weeks after initiation of ART, then every 4-8 weeks|
|ART regimen is modified due to drug toxicity||Will depend on previous CD4 counts||4-8 weeks after modification of regimen|
|ART regimen is modified due to virologic failure||Every 3-6 months||2-4 weeks after initiation of ART, then every 4-8 weeks|
|During the first 2 years of ART||Every 3-6 months||Every 3-4 months|
|While on ART with detectable viremia (>200 copies/mL)||Every 3-6 months||Every 3 months|
| Change in clinical status
(new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy)
|Will depend on the clinical scenario||Every 3 months|
Other Laboratory Monitoring
|At HIV diagnosis||
|At initiation of ART||
|After 2-8 weeks after ART initiation||
|Every 3-6 months||
|Every 6-12 months||
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