HIV and AIDS treatment: protocols and regimens

Modern treatment of HIV infection allows suppression of viral replication in most patients, usually for a fairly long period of time, and slows the progression of the disease to the AIDS stage.

Indications for hospitalization

Hospitalization of patients with HIV infection is carried out taking into account the severity of the condition and clinical data, depending on the presence of a secondary or concomitant disease.

Regime and diet

The regimen and diet for patients are prescribed in accordance with established nosological forms.

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Drug treatment of HIV infection and AIDS

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Etiotropic treatment of HIV infection and AIDS

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Antiretroviral drugs recommended for use

• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): abacavir, zidovudine, lamivudine, didanosine, stavudine, phosphazide.
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz, nevirapine, etravirine.
• Protease inhibitors (PI): atazanavir, indinavir, lopinavir/ritonavir, nelfinavir, fosamprenavir, saquinavir, ritonavir (practically not used as PI, used as a booster, mainly from the PI class), darunavir.

Antiretroviral drugs, doses and regimens for their use

Preparation	Dosage and administration scheme
Abacavir	300 mg 2 times a day
Amprenavir	1200 mg 2 times a day
Atazanavir	400 mg once daily
	300 mg atanazavir and 100 mg ritonavir once daily
Darunavir	600 mg darunavir and 100 mg ritonavir twice daily
Didanosine	250 or 400 mg once a day depending on body weight
Zidovudine	200 mg 3 times a day
Indinavir	800 mg indinavir and 100 mg (or 200 mg) ritonavir 2 times daily
	800 mg 3 times a day
Efavirenz	600 mg once daily
Lamivudine	150 mg 2 times a day
Lopinavir/ritonavir	399 / 99.9 mg 2 times a day
Nevirapine	200 mg 1 time per day for 14 days, then 2 times per day
Nelfinavir	750 mg 3 times a day
	1250 mg 2 times a day
Ritonavir	100 mg or 200 mg 2 times daily (used to boost other protease inhibitors)
Saquinavir	1200 mg 3 times a day
	1000 mg saquinavir and 100 mg ritonavir twice daily
	1500 mg saquinavir and 100 mg ritonavir once daily
	2000 mg saquinavir and 100 mg ritonavir once daily
Stavudine	30 or 40 mg once a day depending on body weight
Fosamprenavir	1400 mg 2 times a day
	700 mg fosamprenavir and 100 mg ritonavir twice daily
	1400 mg fosamprenavir and 200 mg ritonavir once daily
Enfuvirtide	90 mg 2 times a day (subcutaneously)
Etravirine	200 mg 2 times a day

Factors to consider when deciding whether to prescribe antiretroviral drugs.

• The degree of immunodeficiency (assessed based on the number of CD4 lymphocytes).
• The risk of disease progression (determined by measuring the viral load).
• The patient's readiness and desire to begin treatment.
• Patient awareness of possible side effects of drugs and changes in quality of life.
• Selection of initial therapy to achieve a sustained virological response and maintaining the maximum choice of drug combinations for subsequent use.
• Pharmacoeconomic feasibility of choosing different HAART regimens.

There are certain indications for starting treatment for HIV infection.

Various drug regimens have been developed (first-, second- and third-line regimens), based on clinical studies of the effectiveness of antiretroviral drugs.

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Indications for highly active antiretroviral therapy

Clinical picture	CD4+ lymphocyte count	Serum HIV RNA concentration	Recommendations
Presence of AIDS-indicating illnesses or severe symptoms	Any value	Any value	Starting or continuing treatment
Asymptomatic course	The CD4+ lymphocyte count exceeds 350 cells per 1 µl	The viral load value does not exceed 100,000 copies/ml	The patient continues to be monitored. HAART is not used.
		The viral load value exceeds 100,000 copies/ml	The need for HAART is discussed collectively. HAART may be recommended in the case of a rapid decrease in CD4+ lymphocytes (>50 cells in 1 μl per year), age over 55 years, or HIV/HCV co-infection.
	The CD4+ lymphocyte count is 201-350 cells per 1 µl	The viral load value does not exceed 20,000 copies/ml	Most experts recommend postponing HAART. EACS recommends HAART regardless of viral load
		Viral load value exceeds 20,000 copies; ml	HAART is indicated
		Any viral load value	HAART is recommended for use in cases of high risk of rapid progression of HIV infection (if the patient is under 50 years old and periodically uses psychoactive substances intravenously). There is a risk of low adherence
	The number of CD4 lymphocytes does not exceed 200 cells in 1 µl	Any level of viral load	HAART is recommended

Treatment regimens using first-line drugs

One drug or combination from columns A and B (use the preferred category)
	Column A	Column B
Selection schemes	NNRTI: efavirenz	Zidovudine and lamivudine (or Combivir) Phosphazid and lamivudine Abacavir and lamivudine (or Kivexa) - regimen of choice when screening for HW B-5701 is possible
	PI: atazanavir and ritonavir
	IP: lopinavir or ritonavir (2 times a day)
	IP: fosamprenavir and ritonavir (2 times a day)
Alternative schemes	NNRTI: nevirapine	Abacavir and lamivudine (or Kivexa) Didanosine and lamivudine
	IP: atazanavir
	PI: fosamprenavir
	IP: fosamprenavir and ritonavir (once daily)
	IP: lopinavir or ritonavir (once daily)
Other drugs sometimes used in first-line therapy	Nelfinavir	Stavudine and lamivudine
	Ritonavir and saquinavir
	Zidovudine, lamivudine, and abacavir (or trizivir)
	Combivir and abacavir
	Zidovudine and Kivexa

Treatment regimens using second-line drugs (after assessing the reasons for the failure of the first treatment regimen and conducting a virus resistance test)

Initial scheme	Recommended changes in therapy
2 NRTIs and NNRTIs	2 NRTIs (based on viral resistance testing results) and PIs (with or without ritonavir)
2 NRTIs and PIs (sometimes ritonavir is added)	2 NRTIs (based on viral resistance testing results) and NNRTIs
	2 NRTIs (based on viral resistance testing results) and an alternative PI (with ritonavir, based on viral resistance testing results)
3 NIOTs	2 NRTIs and NNRTIs or PIs (with or without ritonavir based on test results)

Treatment regimens using third-line drugs (subsequent HAART failures)

Used schemes	Recommendations for changing therapy
2 NRTIs and PIs or 3 NRTIs	NRTIs (based on the results of virus resistance testing), NNRTIs (if NNRTIs have not been used previously or the resistance test indicates the sensitivity of the virus to drugs) and PIs, including new generation ones, such as darunavir with or without ritonavir, based on the results of testing)
NRTIs, NNRTIs and IPs	More than one NRTI drug is prescribed in combination with a new PI (boosted with ritonavir based on testing results) and enfuvirtide

The principle of the approach to treating patients with HIV infection is lifelong use of antiretroviral drugs.

Pathogenetic therapy and treatment regimens for secondary diseases most frequently registered in HIV-infected patients

Treatment of HIV infection should be combined with therapy of secondary and concomitant diseases. In most cases, treatment of such diseases has priority over the initiation of HAART, since the severity of the patient's condition determines the presence of a particular nosology.

Cytomegalovirus infection

Treatment of manifest cytomegalovirus infection.

• A three-week therapy is carried out with ganciclovir (cymevene) at a dose of 5 mg/kg 2 times a day intravenously slowly over the course of an hour.
• Valganciclovir (Valcyte) is prescribed at a dose of 900 mg 2 times a day orally for 3 weeks (less preferred).

Treatment and secondary prevention of active cytomegalovirus infection.

• Cymevene is prescribed at a dose of 1 g 3 times a day for 30 days (enterally).
• Valcyte is used at 900 mg once a day for 30 days (enterally).
• A four-week therapy is carried out with cymevene at 5 mg/kg once a day intravenously by drip over the course of an hour (less preferable).

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Herpes infection caused by the herpes simplex virus type 3 (Varicella Zoster)

• Acyclovir is prescribed at 800 mg 5 times a day (orally) or 750-1000 mg 3 times a day (intravenously).
• Valaciclovir is used at 1 g 3 times a day (orally).
• Use famciclovir 500 mg 3 times a day for 7-10 days (orally).

Pneumocystis pneumonia

Selection scheme.

• Biseptol 120 mg/kg per day in 4 doses for 21 days.

Alternative schemes.

• Clindamycin at a dose of 600-900 mg intravenously every 6-8 hours.
• Clindamycin at a dose of 300-450 mg orally every six hours in combination with primaquine (15-30 mg / kg) orally.

Primary and secondary prevention of Pneumocystis pneumonia (with a CD4 lymphocyte level of less than 200 cells in 1 μl): Biseptol at a dose of 480 mg 2 times a day every other day until the CD4 lymphocyte count increases to 200 cells in 1 μl or more.

Toxoplasmosis (the cerebral form is more often diagnosed)

Treatment of toxoplasmosis begins at the slightest suspicion of this disease, without waiting for the results of the examination.

Selection scheme.

• Prescribe 2 tablets of Fansidar 2 times a day in combination with leucovorin (25 mg) intramuscularly every other day for 6 weeks.

Alternative schemes.

• Biseptol is used at 60 mg/kg per day (in 2 doses) for 6 weeks.
• 5-fluorouracil (at a dose of 1.5 mg/kg per day orally) is used in combination with clindamycin (1.8-2.4 g 2 times per day orally or intravenously) for 6 weeks.
• Doxycycline is prescribed (orally or intravenously, 300-400 mg per day) in combination with clarithromycin (orally, 500 mg 2 times per day) or sulfadiazine (orally, 1000-1500 mg) every six hours for 1.5 months.

Kaposi's sarcoma

HAART is the main method that allows preventing the progression of the disease and achieving clinical improvement. In severe forms of Kaposi's sarcoma, which occurs with the involvement of internal organs in the pathological process, prospidin is prescribed at a dose of 100 mg intramuscularly for 30 days.

Candidal stomatitis

Selection scheme.

• Clotrimazole lozenges (10 mg 5 times daily) until symptoms disappear.

Alternative schemes.

• Fluconazole 100 mg per day until symptoms disappear.
• Nystatin at a dose of 500,000 IU 4-5 times a day until symptoms disappear.
• Itraconazole (suspension) 100 mg daily until symptoms disappear.

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Candidal esophagitis

Selection scheme.

• Fluconazole at a dose of 200 mg per day orally (up to 800 mg per day) for 2-3 weeks.

Alternative schemes.

• Itraconazole capsules 200 mg per day for 2-3 weeks.
• Rarely, usually when it is impossible to prescribe another regimen, amphotericin B is used (at a dose of 0.6 mg/kg per day intravenously) for 10-14 days.

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Cryptococcal meningitis

Selection scheme.

• Amphotericin B (0.7 mg/kg per day intravenously) in combination with 5-flucytosine (orally 100 mg/kg per day) for two weeks. Then fluconazole is prescribed at a dose of 400 mg per day for two months or until the cerebrospinal fluid is sanitized. The final stage is maintenance therapy with fluconazole (200 mg per day) until the number of CD4+ lymphocytes increases to 200 cells in 1 μl or more.

Alternative schemes.

• Amphotericin B (0.7-1.0 mg/kg per day intravenously) for two weeks. Then fluconazole (400 mg orally per day) is used for 8-10 weeks.
• Fluconazole (orally 400-800 mg per day) in combination with 5-flucytosine (orally 100 mg/kg per day) for 6-10 weeks.
• Ambisome is used (4 mg/kg per day intravenously) for two weeks. Then fluconazole is used (400 mg per day) for 8-10 weeks.

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Mycobacterial infection

When treating mycobacterioses found in HIV-infected patients, standard drugs are prescribed and standard dosage regimens are used.

Features of therapy of mycobacterial infection in HIV-infected patients.

• If the number of CD4+ lymphocytes decreases (less than 100 cells in 1 μl), patients are prescribed rifampicin or rifabutin at least 3 times a week, since less frequent use of the drugs leads to the formation of resistance of the pathogen. The duration of treatment is determined individually.
• In case of a strong decrease in the number of CD4+ lymphocytes (less than 100 cells in 1 μl), at least four drugs are used for the treatment of tuberculosis for 2 months; then two drugs are left (they are used for 4.5 months). If the sputum analysis after 2 months of treatment yields positive results, then the therapy is carried out for the next 7 months.
• If extrapulmonary forms of tuberculosis are detected, standard treatment regimens for pulmonary tuberculosis are prescribed. The exceptions are miliary tuberculosis, tuberculosis of bones and joints, tuberculous meningitis (treatment is carried out for 12 months).
• Treatment of tuberculosis and HIV infection cannot be started simultaneously due to overlapping side effects of the drugs used, adverse drug interactions, requirements for compliance with the drug regimen, and the likelihood of paradoxical reactions associated with the restoration of the immune system. HAART and anti-tuberculosis treatment can be started simultaneously with a sharp decrease in CD4+ lymphocytes to 50 cells in 1 μl (if the patient tolerates anti-tuberculosis therapy well).
• It is not recommended to use PIs and NNRTIs during anti-tuberculosis therapy, with the exception of efavirenz, ritonavir, and the combination of ritonavir and saquinavir.

Hepatitis

The initial stage of antiviral therapy for chronic hepatitis C in patients with HIV infection is presented in the table.

Initial stages of antiviral therapy for chronic viral hepatitis C in patients with HIV infection

CD4 lymphocyte count (cells/µl)	Principles of treatment of chronic hepatitis C and HIV infection
<200	It is advisable to carry out HAART before the start of treatment for chronic hepatitis C, given the high risk of opportunistic infections, as well as the possibility of a decrease in the number of CD4_ lymphocytes during interferon therapy.
201-500	If the number of CD4+ lymphocytes increases to 350 in 1 μl and above, treatment for CHC can be started. In other cases, the issue is decided collegially. Treatment of secondary diseases has priority over antiviral therapy for viral hepatitis (the issue of treatment is considered later).
>500	The risk of infection progression is low and HAART can be delayed. It is most preferable to start treatment for HCV

The administration of immunoglobulins to patients with HIV infection can be considered as pathogenetic therapy.

Indications for the use of immunoglobulins.

• Immunodeficiency (for replacement purposes).
• Idiopathic thrombocytopenia with an autoimmune mechanism of development (20 g of protein per day).
• Severe bacterial and viral secondary and concomitant diseases.

The dosage of the drugs and the course of treatment depend on the degree of immunodeficiency, the severity of the patient's condition, and the drug from the immunoglobulin group.

• Human immunoglobulin normal (gamimun H), immunoglobulin IG VENA N IV Single dose is 25-50 ml (intravenously by drip), three to ten infusions are administered. Repeated administration is carried out only after 24 hours (or 48 hours or after 72 hours).
• Octagam is prescribed at 200-400 mg/kg (intravenously) every 3-4 weeks.

Medical and social expertise

When conducting a medical and social examination of HIV-infected patients, the severity of the clinical signs of the disease (the stage of HIV infection) is taken into account. Social reasons - the impossibility of further work (for example, a surgeon, dentist, obstetrician-gynecologist, resuscitator, medical personnel performing parenteral manipulations, employees of a blood transfusion station and biomedical preparation factories whose professional responsibilities include the preparation of drugs for parenteral administration) - are the basis for determining permanent loss of working capacity. In the event that professional reorientation of these persons is impossible, Group III disability may be issued.

Issues of temporary disability are resolved strictly individually, based on the severity and duration of various clinical signs, guided by the “Instructions on the rules for assessing temporary disability for insured persons”, with subsequent additions and corrections.

To determine the degree of permanent disability in HIV-infected patients, the Karnofsky index is used.

• If the Karnofsky index is 100-90%, then the patient’s activity is completely preserved.
• The patient's ability to perform strenuous physical work is limited (can perform light work) with an index value of 80-70%.
• If the Karnofsky index does not exceed 60-30%, then the patient is able to move and take care of himself, but cannot work (lies or sits less than 50% of the waking period).
• Limited ability to care for oneself, the patient lies or sits more than 50% of waking time - the index value is 40-30%.
• The Karnofsky index does not exceed 20-10%: in this case, the patient is completely immobilized and cannot take care of himself.

During the stage of primary clinical manifestations of HIV infection (stages II and III), patients’ ability to work is completely preserved (Karnofsky index – 90-100%).

At the stage of secondary diseases (stage IVA), the working capacity of patients is also fully preserved (Karnovsky index - 90-100%). At the same time, some patients experience the development of persistent asthenic disorders and the formation of a psychoorganic syndrome; this leads to a decrease in the ability to work in full (Karnovsky index - 70-80%). In this case, given the nature of professional activity, it is recommended to issue the patient with disability group III.

At later stages of HIV infection (stage IVB), relapses of secondary diseases become more frequent and most patients require hospitalization (repeatedly), which leads to persistent loss of ability to work (Karnovsky index - 50-80%). In this case, the patient is transferred to disability group II or III. The exception is persistent lesions of the peripheral nervous system with severe motor impairment (Karnovsky index is 10-40%). The patient is assigned disability group I.

At the stage of secondary diseases (stage IVB), all patients are found to have persistent impairment of working capacity (Karnovsky index - 10-50%). Depending on the nature and severity of the lesions, it is recommended to establish I or II disability group.

Clinical examination

In order to organize medical care for patients with HIV infection and to increase the duration and improve the quality of their life, as well as to carry out anti-epidemic measures, it is necessary to ensure maximum coverage of HIV-infected patients with dispensary observation.

All examinations of an HIV-infected patient are performed only after obtaining voluntary informed consent. It is recommended to actively invite HIV-infected patients to periodic examinations, but at the same time, the rights of people to refuse examination and treatment must not be violated. The patient also has the right to choose a medical institution.

The medical examination of HIV-infected patients is carried out in accordance with regulatory documents.

Outpatient observation of HIV-infected patients is carried out in outpatient and polyclinic settings at the place of residence or in a healthcare facility (for continuous provision of medical care, the patient is assigned, for example, to a polyclinic or hospital).

When registering an HIV-infected patient for dispensary monitoring, it is necessary to familiarize him/her with the algorithm and purpose of dispensary monitoring, the schedule of visits to the attending physician and specialists, the possibility of performing laboratory and instrumental studies. In this case, the patient's consent to conduct dispensary monitoring (or refusal of medical care) in writing is required.

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Activities carried out during the initial examination

• Examination by the attending physician (consultation, collection of anamnesis, complete physical examination).
• Registration of secondary diseases, their dynamics and course.
• Registration of concomitant diseases.
• Assessment of the patient's quality of life (according to the Karnofsky scale).
• Chest X-ray (if the examination has not been performed within the last six months).
• Ultrasound of the abdominal organs (liver, gallbladder, pancreas) and kidneys.
• ECG.
• Consultation with an ophthalmologist (examination of the fundus).
• Consultation with an otolaryngologist (hearing acuity and vestibular function are examined).
• Consultation with a neurologist.
• Dentist consultation.
• Gynecologist consultation (for women).
• A test of blood serum or plasma for antibodies to HIV using the ELISA method.
• Complete blood count (hemoglobin and hematocrit: platelets, erythrocytes and leukocytes, leukocyte formula, ESR).
• Blood biochemistry (creatinine and urea; activity of ALT, AST, alkaline phosphatase, LDH, CPK, amylase or lipase; bilirubin and its fractions; glucose, total protein and fractions).
• General urine analysis.
• Determination of markers of viral hepatitis B, C, delta.
• Serological analysis - to detect markers of syphilis, antibodies to cytomegalovirus, toxoplasma, HSV, P. carinii.
• Stool examination for helminth eggs and protozoa: culture for the diagnosis of salmonellosis.
• Tuberculin test.
• Immunological examination (immune status).
• Determination of HIV RNA concentration in blood serum.

Repeated planned examinations are carried out to promptly identify indications for prescribing antiretroviral therapy (or to correct it). The scope of the planned repeated examination depends on the stage of the disease and the level of CD4 lymphocytes.

Periods of medical examination

Stage of the disease	The number of CD4+ lymphocytes in 1 µl of blood	Interval (in weeks)
II, III	>500	24
	<500	12
	Unknown	24
IVA, IVB	>500	24
	<500	12
	Unknown	12
IVB (AIDS)		Depending on the clinical picture

It is recommended to consult with specialists (dentist, ophthalmologist, neurologist) once every six months, and to be examined by other specialists as indicated.

A study to detect markers of viral hepatitis B and viral hepatitis C and syphilis is also performed once every six months.

Chest X-ray and abdominal ultrasound are performed once a year (if the number of CD4+ lymphocytes increases to more than 500 cells in 1 μl) or 2 times a year (if the number of CD4+ lymphocytes decreases to 500 cells in 1 μl or less).

A CT or MRI scan of the brain is recommended to be performed when there is a sharp decrease in the number of CD4+ lymphocytes (less than 200 cells in 1 μl).

Unscheduled examinations should be carried out if any signs of HIV infection progression are detected or if concomitant diseases develop. Additional examinations are performed at the discretion of the attending physician.