HIV AIDS medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Ammu Susheela, M.D. [3]; Tarek Nafee, M.D. [4]
Overview
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.
Medical Therapy
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. [1]
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.
Uncontrolled viremia causes inflammation and immune activation, which has an overall effect on cardiovascular, renal and hepatic systems. Controlling viremia also controls these effects.
Anti Retroviral Therapy (ART)
- 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.[2][3]
- Fusion inhibitors (eg, enfuvirtide) are not approved for treatment-naive patients.
Anti Retroviral Regimens
WHO Recommendations in Adults
▸ Click on the following categories to expand treatment regimens.
ARV Regimens ▸ First-Line Regimens ▸ Second-Line Regimens |
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National Institute of Health (NIH) Recommendations
▸ Click on the following categories to expand treatment regimens.
Recommended Regimens ▸ NNRTI-Based Regimen ▸ PI-Based Regimen ▸ INSTI-Based Regimen Alternative Regimens ▸ PI-Based Regimen ▸ INSTI-Based Regimen |
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Anti Retroviral Drug Classes
Drug Name | Dose | Adverse Events |
---|---|---|
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||
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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. |
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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) | ||
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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 |
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200 mg BID | Rash, Stevens-Johnson syndrome, nausea |
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200 mg once daily for 14 days, then 200 mg BID or 400 mg once daily | Rash, Stevens-Johnson syndrome, nausea, hepatitis |
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25 mg once daily | Rash, depression, insomnia, headache, hepatotoxicity |
Protease Inhibitors (PIs) | ||
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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 |
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800 mg once daily | Skin rash, Stevens-Johnson syndrome, hepatotoxicity, diarrhea, nausea, headache, hyperlipidemia, fat maldistribution, hyperglycemia. |
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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. |
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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. |
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1250 md BID or 750 mg TID | Diarrhea, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels. |
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100-400 mg/d q12-24h | Diarrhea, nausea, vomiting, paresthesia, hyperlipidemia, hepatitis, asthenia, taste perversion, hyperglycemia, fat maldistribution. |
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1000 mg BID | Diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, fat maldistribution, PR interval prolongation, insulin resistance/diabetes mellitus. |
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500 mg BID | Hepatotoxicity, skin rash, hyperlipidemia, hyperglycemia, fat maldistribution. |
Integrase Inhibitors | ||
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50 mg q12-24h | Rash, insomnia, headache. |
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150 mg once daily | Nausea, diarrhea, decrease bone density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients. |
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400 mg BID | Rash, Steven-Johnson syndrome, toxic epidermal necrolysis, nausea, headache, diarrhea, pyrexia, CPK elevation. |
Fusion Inhibitor | ||
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90 mg SQ BID | Local injection reactions, increased incidence of bacterial pneumonia, rash, fever, nausea. |
CCR5 Antagonist | ||
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150-600 mg BID | Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity. |
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5] |
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 |
Recommendations for Initiating Antiretroviral Therapy
- 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:
- Pregnancy (AI)
- History of an AIDS-defining illness (AI)
- HIV associated nephropathy (HIVAN) (AII)
- HIV/hepatitis B virus (HBV) coinfection (AII)
- 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.
Current Recommended Initial Oral ART for Most Persons with HIV Infection[6]
Bictegravir– FTC–TAF (50 mg/200 mg/25 mg),once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, immune reconstitution inflammatory syndrome (IRIS), lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Dolutegravir (50 mg),once daily
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Dolutegravir–3TC (50 mg/300 mg), once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), IRIS, lactic acidosis, hepatic steatosis.
- Do not use with lamivudine resistance (M184V or M184I mutation) or HBV infection; not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class B or C liver function; contraindicated with dofetilide; avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine; use with caution with metformin.
- Dolutegravir–3TC is not recommended for patients with rapid start of ART or for patients with chronic HBV infection, HIV RNA greater than 500,000 copies per milliliter, or a CD4 cell count of less than 200 cells/mm3.
Raltegravir (600 mg), two tablets once daily
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily
- Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), headache, IRIS, lactic acidosis, hepatic steatosis.
- Not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class C liver function, contraindicated with dofetilide or rifampin, avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine, and use with caution with metformin.
Abbreviations
FTC emtricitabine
TAF tenofovir alafenamide fumarate,
TDF tenofovir disoproxil fumarate,
3TC lamivudine.
Treatment Failure
Definitions of Treatment Failure | |
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Clinical Failure |
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CD4 Cell Failure |
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Virological Failure |
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Table adapted from WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection[4] |
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 [7] |
Special Considerations
- 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.[8][9]
- It would take more than the lifetime of an individual to be cleared of HIV infection using HAART.[10]
- 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.[11][12][13]
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.[14]
Treatment Adherence
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.[15][16][17]
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.
Virologic Response
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.[18][19] It is thus useful in predicting clinical progression.
Viral load reduction may be more rapid in following patients:[20]
- 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.
Virologic Failure
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.[21]
Two main causes of the failure are:
- Drug resistance.
- Failure of the drugs to reach the target site.
Viral Blips
It refer to an isolated low-level of detectable HIV RNA (>50 to 500 copies/mL) that occurs during long-term monitoring on a stable ART regimen.[22]
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 |
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5] |
Other Laboratory Monitoring
Time-point | Laboratory Tests | ||
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At HIV diagnosis |
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At initiation of ART |
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After 2-8 weeks after ART initiation |
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Every 3-6 months |
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Every 6-12 months |
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Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5] |
Treatment Regimen
- 1.1. Integrase strand transfer inhibitor-based regimens
- Preferred regimen (1): Dolutegravir 50 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative
- Preferred regimen (2): Dolutegravir 50 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Preferred regimen (3): Elvitegravir 150 mg-Cobicistat 150 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd in patients with estimated CrCl ≥ 70 mL/min/1.73
- Preferred regimen (4): Raltegravir 400 mg PO bid AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Efavirenz 600 mg PO qd OR Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg PO qd AND (Tenofovir 300 mg PO qd OR Emtricitabine 200 mg PO qd) for patients with CD4 count >200 cells/microL
- Alternative regimen (3): Raltegravir 400 mg PO bid AND (Abacavir 600 mg PO qd OR Lamivudine 300 mg PO qd) in patients who are HLA-B*5701-negative
- 1.2. Protease inhibitor-based regimen
- Preferred regimen: Darunavir 800 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Atazanavir 300 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (2): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (3): (Darunavir 800 mg-Cobicistat 150 mg PO qd OR Darunavir 800 mg-Ritonavir 100 mg PO qd) AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (4): Darunavir 800 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (5): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative and with pre-treatment HIV RNA <100,000 copies/mL
- Alternative regimen (6): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (7): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- 1.3. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Alternative regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- 1.4. Other regimen options
- 1.4.1. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Preferred regimen (1): Efavirenz 600 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.
- 1.4.2. Other regimens when tenofovir or abacavir cannot be used
- Preferred regimen (1): Darunavir 800 mg-Ritonavir 100 mg PO qd AND Raltegravir 400 mg PO qd only for patients with pre-treatment HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3.
- Preferred regimen (2): Lopinavir 400 mg-Ritonavir 100 mg PO bid AND Lamivudine 300 mg PO bid
- 1.5. Pediatric doses
- Abacavir 300 mg PO bid
- Lamivudine 4 mg/kg/dose PO bid; maximum 150 mg PO bid
- Stavudine 1 mg/kg/dose PO bid
- Tenofovir 8 mg/kg/dose PO bid
- Zidovudine 180-240 mg/m2/dose PO bid or 160 mg/m2/dose PO tid (range 90 mg/m2/dose-180 mg/m2/dose)
- Lopinavir 400 mg PO bid
- Nelfinavir 50 mg/kg/dose PO bid
- Raltegravir 300 mg PO bid
- Didanosine
- 20 to < 25 kg: 200 mg PO qd
- 25 to < 60 kg: 250 mg PO qd
- ≥60 kg: 400 mg PO qd
- 10 to < 15 kg: 200 mg PO qd
- 15 to <20 kg: 250 mg PO qd
- 20 to < 25 kg: 300 mg PO qd
- 25 to < 32.5 kg: 350 mg PO qd
- 32.5 to <40 kg: 400 mg PO qd
- ≥ 40 kg: 600 mg PO qd
- Nevirapine maximum 200 mg per dose
- Between 1 day and 8 years: 200 mg/m2/dose PO qd for 14 days, then 200 mg/m2/dose PO bid
- 8 years and above: 120-150 mg/m2/dose PO qd for 14 days, then 120-150 mg/m2/dose PO bid
- Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
- Note (2): Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
- Note (3): Rilpivirine should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
- Note (4): Efavirenz should not be used in pregnant women.
- 2. Pre-exposure prophylaxis (PrEP)
- Preferred regimen: Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd for ≤90-days
- Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
- Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
- Note (3): At 3 months and every 6 months thereafter, assess renal function.
- Note (4): Every 6 months, test for bacterial STIs.
- 3. Post- exposure prophylaxis
- Preferred regimen: Raltegravir 400 mg PO bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- Preferred basic regimen for low-risk exposures (Eg: mucus membrane):
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
- Preferred expanded regimen for high-risk exposure (Eg: percutaneous needle stick)
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Note: Ideally therapy should be started within hours of exposure and continued for 28 days.
- 4. Perinatal antiretroviral regimen
- 4.1. Antepartum
- 4.1.1. Protease inhibitor-based regimen
- Preferred regimen: (Tenofovir 300 mg-Emtricitabine 200 mg PO qd (fixed dose combination) OR Tenofovir 300 mg-Lamivudine 300 mg PO qd OR Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND (Atazanavir 300 mg-Ritonavir 100 mg PO qd OR Lopinavir 400 mg-Ritonavir 100 mg PO qd)
- 4.1.2. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:
- Preferred regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg (fixed dose combination) PO qd
- Preferred regimen (2): Efavirenz 600 mg-Tenofovir 300 mg-Lamivudine 300 mg PO qd
- Alternative regimen: (Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND Efavirenz 600 mg PO qd
- 4.2. Intrapartum
- Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
- Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous Zidovudine 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.
- 4.3. Postpartum
- Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.
- 5. Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV
- 5.1 Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis
- Preferred regimen: Zidovudine (ZDV) 100 mg PO given at birth and continued till six weeks
- Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- 5.2. Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis
- Nevirapine
- Dose based on birth weight, initiated as soon after birth as possible.
- Birth weight 1.5 to 2 kg: 8 mg/dose orally.
- Birth weight >2 kg: 12 mg/dose orally.
- AND
- Zidovudine (ZDV)
- Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- Note (1): Three doses in the first week of life.
- Note (2): First dose within 48 hours of birth (birth to 48 hrs).
- Note (3): Second dose 48 hours after first.
- Note (4): Third dose 96 hours after second.
- Nevirapine
Primary Prophylaxis against Opportunistic Infections in Persons with HIV Infection[25]
Prophylaxis against Pneumocystis jirovecii
- Indications: CD4 count <200 cells/mm3 or thrush
- Drugs used:
- Trimethoprim–sulfamethoxazole one double-strength tablet (160 mg of trimethoprim and 800 mg of sulfamethoxazole) daily or 3 times/week
- Dapsone 100 mg, orally once daily
- Pentamidine 300 mg, aerosolized through nebulizer monthly
- Atovaquone 1500 mg, orally (liquid suspension) daily
Prophylaxis against cryptococcus
- Indications: CD4 count <100 cells/mm3 and positive serum cryptococcal antigen
- Drug used: fluconazole 200 mg, orally once daily
Prophylaxis against histoplasmosis
- Indications: CD4 count <150 cells/mm3 in areas where histoplasmosis is endemic
- Drug used: itraconazole 200 mg, orally once daily
Prophylaxis against Mycobacterium avium complex
It is no longer recommended in patient with rapid initiation of ART
Management of HIV-patients
The 2021 CDC STD guidelines recommend the following steps to be taken with every patient diagnosed with HIV:[26]
- Link persons with HIV infection to care and start them on ART as soon as possible.
- Report cases (in accordance with local requirements) to public health and initiate partner services.
- Provide prevention counseling to persons with diagnosed HIV infection.
- Ensure all persons with HIV infection are informed that if they achieve and maintain a suppressed viral load, they have effectively no risk for transmitting HIV. Stress that a suppressed viral load is not a substitute for condoms and behavioral modifications because ART does not protect persons with HIV against other STIs.
- Provide additional counseling, either on-site or through referral, about the psychosocial and medical implications of having HIV infection.
- Assess the need for immediate medical care and psychosocial support.
- Link persons with diagnosed HIV infection to services provided by health care personnel experienced in managing HIV infection. Additional services that might be needed include substance misuse counseling and treatment, treatment for mental health disorders or emotional distress, reproductive counseling, risk-reduction counseling, and case management. Providers should follow up to ensure that patients have received services for any identified needs.
- Persons with HIV infection should be educated about the importance of ongoing medical care and what to expect from these services.
References
- ↑ Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M (2005). "Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study". Lancet. 366 (9483): 378–84. doi:10.1016/S0140-6736(05)67022-5. PMID 16054937. Retrieved 2012-02-15.
- ↑ Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC (2003). "Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection". N. Engl. J. Med. 349 (24): 2304–15. doi:10.1056/NEJMoa030265. PMID 14668456. Retrieved 2012-02-16. Unknown parameter
|month=
ignored (help) - ↑ Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S (2010). "Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study". Clin. Infect. Dis. 51 (7): 855–64. doi:10.1086/656363. PMID 20735258. Retrieved 2012-02-16. Unknown parameter
|month=
ignored (help) - ↑ 4.0 4.1 "WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection" (PDF).
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014".
- ↑ Saag MS (2021). "HIV Infection - Screening, Diagnosis, and Treatment". N Engl J Med. 384 (22): 2131–2143. doi:10.1056/NEJMcp1915826. PMID 34077645 Check
|pmid=
value (help). - ↑ "WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS" (PDF).
- ↑ Martinez-Picado J, DePasquale MP, Kartsonis N; et al. (2000). "Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection". Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10948&ndash, 10953. PMID 11005867.
- ↑ Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV. (2002). "Guidelines for using antiretroviral agents among HIV-infected adults and adolescents". Ann. Intern. Med. 137 (5 Pt 2): 381&ndash, 433. PMID 12617573.
- ↑ Blankson JN, Persaud D, Siliciano RF (2002). "The challenge of viral reservoirs in HIV-1 infection". Annu. Rev. Med. 53: 557&ndash, 593. PMID 11818490.
- ↑ Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection". N. Engl. J. Med. 338 (13): 853&ndash, 860. PMID 9516219.
- ↑ Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS (2003). "Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?". AIDS. 17 (5): 711&ndash, 720. PMID 12646794.
- ↑ Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration (2003). "Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies". Lancet. 362 (9385): 679&ndash, 686. doi:10.1016/S0140-6736(03)14229-8. PMID 12957089.
- ↑ "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection" (PDF). Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. 2005-11-03. Retrieved 2006-01-17.
- ↑ Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project (2001). "Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study". Arch. Intern. Med. 161 (16): 1962&ndash, 1968. PMID 11525698.
- ↑ Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP (2001). "Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study". J. Acquir. Immune Defic. Syndr. 26 (1): 82&ndash, 92. PMID 11176272.
- ↑ Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS (2002). "Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy". J. Acquir. Immune Defic. Syndr. 31 (2): 211&ndash, 217. PMID 12394800.
- ↑ Thiébaut R, Morlat P, Jacqmin-Gadda H, Neau D, Mercié P, Dabis F, Chêne G (2000). "Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA)". AIDS. 14 (8): 971–8. PMID 10853978. Retrieved 2012-02-19. Unknown parameter
|month=
ignored (help) - ↑ Hughes MD, Johnson VA, Hirsch MS, Bremer JW, Elbeik T, Erice A, Kuritzkes DR, Scott WA, Spector SA, Basgoz N, Fischl MA, D'Aquila RT (1997). "Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team". Ann. Intern. Med. 126 (12): 929–38. PMID 9182469. Unknown parameter
|month=
ignored (help);|access-date=
requires|url=
(help) - ↑ Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, Faye-Niang MA, Diop A, Kuypers JM, Critchlow CW, Respess R, Mullins JI, Kiviat NB (2002). "Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa". J. Infect. Dis. 185 (7): 905–14. doi:10.1086/339295. PMID 11920314. Retrieved 2012-02-19. Unknown parameter
|month=
ignored (help) - ↑ Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT (2010). "Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel". JAMA. 304 (3): 321–33. doi:10.1001/jama.2010.1004. PMID 20639566. Retrieved 2012-02-20. Unknown parameter
|month=
ignored (help) - ↑ Sungkanuparph S, Overton ET, Seyfried W, Groger RK, Fraser VJ, Powderly WG (2005). "Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are equivalent in incidence and prognosis". Clin. Infect. Dis. 41 (9): 1326–32. doi:10.1086/496985. PMID 16206110. Retrieved 2012-02-21. Unknown parameter
|month=
ignored (help) - ↑ "AIDSinfoNIH".
- ↑ Gunthardt, HF; Saag, Michael; Benson, C (Jul 21, 2016). "Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel". JAMA. The JAMA Network (published 2016). 316 (2): 191–210. doi:10.1001/jama.2016.8900. PMC 5012643. PMID 27404187.
- ↑ Saag MS (2021). "HIV Infection - Screening, Diagnosis, and Treatment". N Engl J Med. 384 (22): 2131–2143. doi:10.1056/NEJMcp1915826. PMID 34077645 Check
|pmid=
value (help). - ↑ Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I; et al. (2021). "Sexually Transmitted Infections Treatment Guidelines, 2021". MMWR Recomm Rep. 70 (4): 1–187. doi:10.15585/mmwr.rr7004a1. PMC 8344968 Check
|pmc=
value (help). PMID 34292926 Check|pmid=
value (help).
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