Treatment of HIV and AIDS: protocols and schemes

Modern treatment of HIV infection can suppress viral replication in the majority of patients, as a rule, for a fairly long time and slow the progression of the disease into the stage of AIDS.

Indications for hospitalization

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

Diet and diet

The regime and diet are prescribed to the patients according to established nosological forms.

[1], [2], [3], [4],

Drug treatment of HIV infection and AIDS

[5], [6], [7], [8], [9], [10], [11],

Etiotropic treatment of HIV infection and AIDS

[12]

Antiretroviral drugs recommended for use

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

Antiretroviral medications, doses and regimens for their use

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

Factors to be considered when deciding whether to prescribe antiretroviral drugs.

• The degree of immunodeficiency (evaluated based on the number of CD4-lymphocytes).
• The risk of progressing disease (determined when measuring a viral load).
• Readiness and desire of the patient to begin treatment.
• Awareness of the patient about possible side effects of drugs and about changing the quality of life.
• The choice of starting therapy to achieve a persistent virologic response and maintaining the maximum choice of combinations of drugs for later use.
• Pharmacoeconomic feasibility of the choice of different HAART regimens.

To start treatment for HIV infection, there are certain indications.

Various schemes of drug use (first, second and third-line regimens) have been developed, taking into account clinical trials of the effectiveness of antiretroviral drugs.

[13], [14], [15],

Indications for highly active antiretroviral therapy

Clinical picture	The number of CD4 + lymphocytes	Concentration of HIV RNA in serum	Recommendations
Presence of AIDS-indicative disease or severe symptoms	Any value	Any value	Begin or continue treatment
Asymptomatic current	The number of CD4 + lymphocytes exceeds 350 cells per 1 μl	The value of the viral load does not exceed 100,000 copies / ml	Continue to monitor the patient. HAART do not use
		The value of the viral load exceeds 100,000 copies / ml	Necessity of HAART appointment is discussed collectively. HAART can be recommended with rapid reduction of CD4 + lymphocytes (> 50 cells in 1 μl per year), over 55 years of age or coinfection with HIV / HCV
	The number of CD4 + lymphocytes is 201-350 cells per 1 μl	The value of the viral load does not exceed 20,000 copies / ml	Most specialists recommend postponing HAART. EACS recommends HAART regardless of viral load
		The value of the viral load exceeds 20,000 copies; ml	HAART is shown
		Any value of viral load	HAART is recommended to prescribe at high risk of rapid progression of HIV infection (if a patient younger than 50 years periodically uses psychoactive substances intravenously). There is a risk of low adherence
	The number of CD4-lymphocytes does not exceed 200 cells per 1 μl	Any level of viral load	HAART recommends that

Treatment regimens using first-line drugs

One drug or combination of graphs A and B (use the preferred category)
	Box A	Box B
Selection schemes	NNRTI: Efavirenz	Zidovudine and lamivudine (or combivir) Phosphazide and lamivudine Abacavir and lamivudine (or kievxa) - a selection scheme for screening possibilities on HW B-5701
	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
	PI: atazanavir
	PI: fosamprenavir
	IP: fosamprenavir and ritonavir (once a day)
	IP: lopinavir or ritonavir (once a day)
Other drugs used sometimes in first-line therapy	Nelfinavir	Stavudine and lamivudine
	Ritonavir and saquinavir
	Zidovudine, lamivudine and abacavir (or trizivir)
	Combivir and abacavir
	Zidovudine and kivexa

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

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

Patterns of therapy using third-line drugs (subsequent failures of HAART)

Used Schemes	Recommendations for changing therapy
2 NRTIs and PIs or 3 NRTIs	NRTIs (based on virus resistance test results), NNRTIs (if NNRTIs were not previously used, or a resistance test indicates susceptibility of the virus to drugs) and PIs, including new generation, for example, darunavir with ritonavir or without, based on the results testing)
NRTI, NNRTI and PI	Assign more than one NRTI drug in combination with a new PI (boosted ritonavir based on test results) and enfuvirtide

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

Pathogenetic therapy and regimens for the treatment of secondary diseases, most often recorded 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 takes precedence over HAART, since the severity of the patient's condition determines the presence of a particular nosology.

Cytomegalovirus infection

Treatment of a manifest cytomegalovirus infection.

• A three-week therapy with ganciclovir (cymenevene) at a dose of 5 mg / kg 2 times a day is intravenously slowed for an hour.
• Valganciclovir (Valcit) is administered at a dose of 900 mg 2 times a day for 3 weeks (less preferably).

Treatment and secondary prevention of active cytomegalovirus infection.

• Assign tsimeven in a dose of 1 g 3 times a day for 30 days (enteralno).
• Apply valctite 900 mg once a day for 30 days (enterally).
• 4-week therapy with cymeneven is administered at 5 mg / kg once a day intravenously drip for an hour (less preferably).

[16], [17], [18]

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

• Assign aciclovir 800 mg 5 times a day (orally) or 750-1000 mg 3 times a day (intravenously).
• Apply valaciclovir 1 g 3 times a day (inside).
• Use famciclovir 500 mg 3 times a day for 7-10 days (inside).

Pneumocystis pneumonia

The scheme of choice.

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

Alternative schemes.

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

Primary and secondary prophylaxis of PCP (at a CD4-lymphocyte level of less than 200 cells per 1 μl): Biseptol at a dose of 480 mg 2 times a day every day until the number of CD4-lymphocytes is increased to 200 cells in 1 μl or more.

Toxoplasmosis (more often diagnosed as a cerebral form)

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

The scheme of choice.

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

Alternative schemes.

• Apply biseptol at 60 mg / kg per day (in 2 doses) for 6 weeks.
• Use 5-fluorouracil (1.5 mg / kg per day orally) in combination with clindamycin (1.8-2.4 g 2 times a day orally or intravenously) for 6 weeks.
• Assign doxycycline (inside or intravenously 300-400 mg per day) in combination with clarithromycin (inside 500 mg twice a day) or sulfadiazine (inside 1000-1500 mg) every six hours for 1.5 months.

Kaposi's Sarcoma

HAART is the main method to prevent the progression of the disease and to achieve clinical improvement. With a severe form of Kaposi's sarcoma. Flowing with the involvement of internal organs in the pathological process, prescribe a prospidin at a dose of 100 mg intramuscularly for 30 days.

Candidiasis stomatitis

The scheme of choice.

• Clotrimazole lozenges (10 mg 5 times a day) until the symptoms disappear.

Alternative schemes.

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

[19], [20], [21], [22], [23], [24]

Candid esophagitis

The scheme of choice.

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

Alternative schemes.

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

[25], [26], [27], [28], [29], [30], [31], [32]

Cryptococcal meningitis

The scheme of choice.

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

Alternative schemes.

• Amphotericin B (in a dose of 0.7-1.0 mg / kg per day intravenously) for two weeks. Then apply fluconazole (inside 400 mg per day) for 8-10 weeks.
• Fluconazole (inside 400-800 mg per day) in combination with 5-flucytosine (inside at 100 mg / kg per day) for 6-10 weeks.
• Use ambizom (4 mg / kg per day intravenously) for two weeks. Then fluconazole (400 mg per day) is used for 8-10 weeks.

[33], [34], [35], [36],

Mycobacterial infection

In the treatment of mycobacteriosis found in HIV-infected patients, standard drugs are prescribed and the usual dosing regimens are used.

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

• With a decrease in the number of CD4 + lymphocytes (less than 100 cells in 1 μl), patients are prescribed rifampicin or rifabutin at least 3 times a week, as a less frequent intake of drugs leads to the formation of resistance of the pathogen. The duration of treatment is determined individually.
• With a strong decrease in the number of CD4 + lymphocytes (less than 100 cells per 1 μl), at least four drugs are used for tuberculosis therapy for 2 months; then leave two drugs (they are used for 4.5 months). If sputum analysis results after 2 months of treatment, positive results are obtained, then therapy is carried out for the next 7 months.
• When detecting extrapulmonary forms of tuberculosis, standard treatment regimens for pulmonary tuberculosis are prescribed. Exception is miliary tuberculosis, tuberculosis of bones and joints, tuberculosis meningitis (treatment is carried out for 12 months).
• You can not simultaneously start treatment of tuberculosis and HIV infection due to the superposition of side effects of the drugs used, adverse drug interactions, the requirements for adherence to the regimen of drugs and the probability of paradoxical reactions associated with the restoration of the immune system. HAART and antituberculosis treatment can be started simultaneously with a sharp decrease in CD4 + -lymphocytes up to 50 cells per 1 μl (if the patient tolerates anti-tuberculosis therapy well).
• Do not recommend the use of PIs and NNRTIs in antituberculous therapy, with the exception of efavirenz, ritonavir and a combination of ritonavir and saquinavir.

Hepatitis

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

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

The number of CD4 lymphocytes (cells in μl)	Principles of HCV and HIV treatment
<200	HAART is advisable to carry out before the treatment of HCV, given the high risk of opportunistic infections, as well as the possibility of reducing the number of CD4 _ lymphocytes against the backdrop of interferon
201-500	With an increase in the number of CD4 + lymphocytes to 350 in 1 μl and higher, HCV treatment can be started. In other cases, the issue is resolved collegially. Treatment of secondary diseases has priority over antiviral therapy for viral hepatitis (the issue of treatment is considered later)
> 500	The risk of progression of the infection is low, and HAART can be delayed. It is most preferable to begin treatment with CHC

The appointment of immunoglobulins to HIV-infected patients can be considered as a pathogenetic therapy.

Indications for the use of immunoglobulins.

• Immunodeficiency (with substitutional goal).
• Idiopathic thrombocytopenia with an autoimmune development mechanism (20 g protein per day).
• Heavy bacterial and viral secondary and concomitant diseases.

Doses of drugs and course of treatment depend on the degree of immunodeficiency, the severity of the patient's condition, and also the preparation of the group of immunoglobulins.

• Immunoglobulin normal (hymimun H), immunoglobulin IG VENA N IV Single dose is 25-50 ml (intravenously drip), produce from three to ten infusions. Re-administration is performed only after 24 hours (or 48 hours or 72 hours).
• Octagam appoint 200-400 mg kg (intravenously) every 3-4 weeks.

Medical and social expertise

When carrying out medical and social expertise 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, surgeon, dentist, obstetrician-gynecologist, resuscitator, medical personnel, parenteral manipulation, blood transfusion station workers and biomedical plants, whose professional duty includes preparation for parenteral administration) is the basis for determination of permanent disability. In case of impossibility of professional reorientation of the specified persons the III group of physical inability can be made out.

The issues of temporary incapacity for work are decided strictly on an individual basis, based on the severity and duration of various clinical signs, guided by the "Instruction on the rules for examination of temporary incapacity for the insured", with subsequent additions and corrections.

To determine the extent of persistent loss of ability to work for HIV patients, the Karnovsky Index is used.

• If the Karnovsky index is 100-90%, then the patient's activity is fully preserved.
• The ability of the patient to work hard is limited (can perform light work) with an index value of 80-70%.
• If the value of the Karnovsky index does not exceed 60-30%. The patient is able to move and take care of himself, but can not work (lies or sits less than 50% of the waking period).
• Restriction of the ability to care for themselves, the patient lies or sits more than 50% of the waking time - the value of the index is 40-30%.
• The Karnowski index does not exceed 20-10%: while the patient is completely immobilized and can not care for himself.

During the stage of primary clinical manifestations of HIV infection (stages II and III), the patients' work capacity is fully preserved (the Karnovsky index is 90-100%).

At the stage of secondary diseases (stage IVA), the work capacity of patients is also preserved completely (Karnovsky index - 90-100%). At the same time, in some patients, the development of persistent asthenic disorders and the formation of a psychoorganic syndrome are noted; this leads to a decrease in the ability to work in full (the Karnovsky index - 70-80%). In this case, taking into account the nature of the professional activity, it is recommended that a third group of disability be issued to the patient.

At later stages of HIV infection (stage IVB), the recurrence of secondary disease recurrence is noted and there is a need for hospitalization (repeatedly) of the majority of patients, which leads to permanent disability (Karnovsky index - 50-80%). In this case, the patient is transferred to the II or III group of disability. The exception is persistent lesions of the peripheral nervous system with pronounced impairments of motor functions (the Karnovsky index is 10-40%). The patient is issued a first group of disability.

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

Clinical examination

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

All examinations of an HIV-infected patient are performed only after receiving voluntary informed consent. It is recommended to actively invite HIV-infected patients to periodic examinations, but one should not violate people's right to refuse examination and treatment. The patient also has the right to choose a medical facility.

Clinical examination of HIV-infected patients is carried out, guided by regulatory documents.

Clinical follow-up of HIV-infected patients is carried out in outpatient settings at the place of residence or in the health facility (for permanent medical care the patient is attached, for example, to a polyclinic or a hospital).

When the HIV-infected patient is placed on the dispensary record, it is necessary to familiarize him with the algorithm and purpose of dispensary follow-up, schedule visits to the attending physician and narrow specialists, and the ability to perform laboratory and instrumental studies. At the same time, the patient's consent to carry out a dispensary observation (or refusal of medical assistance) in writing is necessary.

[37], [38]

Measures taken during the primary examination

• Examination by the attending physician (counseling, collection of anamnesis, complete physical examination).
• Registration of secondary diseases, their dynamics and course.
• Registration of concomitant diseases.
• Assessment of the quality of life of the patient (according to the Karnovsky scale).
• Radiography of the chest (if the study was not performed within the last six months).
• Ultrasound of the abdominal cavity (liver, gallbladder, pancreas) and kidney.
• ECG.
• Consultation of the ophthalmologist (examine the fundus).
• Consultation of the otorhinolaryngologist (investigate the severity of the hearing and vestibular function).
• Consultation of a neurologist.
• Consultation of the dentist.
• Consultation of a gynecologist (for women).
• Study serum or plasma blood for antibodies to HIV using the ELISA method.
• General blood test (hemoglobin and hematocrit: platelets, erythrocytes and leukocytes, leukocyte formula, ESR).
• Biochemical blood test (creatinine and urea, activity of ALT, ACT, APF, LDH, CK, amylase or lipase, bilirubin and its fractions, glucose, total protein and fractions).
• General urine analysis.
• Definitions of markers of viral hepatitis B ,. C, delta.
• Serological analysis - to detect markers of syphilis, antibodies to cytomegalovirus. Toxoplasma, HSV, P. Carinii.
• Study of feces for eggs of worms and protozoa: sowing for the diagnosis of salmonellosis.
• Sample with tuberculin.
• Immunological examination (immune status).
• Determination of the concentration of HIV RNA in blood serum.

Repeated routine examinations are carried out for the timely detection of indications for the appointment of antiretroviral therapy (or for its correction). The amount of planned re-examination depends on the stage of the disease and the level of CD4-lymphocytes.

Terms of clinical 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

Consultations of narrow specialists (dentist, ophthalmologist, neurologist) are recommended to be performed every six months, examination by other specialists - according to indications.

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

Chest radiography and ultrasound of the abdominal cavity are performed once a year (with an increase in the number of CD4 + lymphocytes, more than 500 cells per 1 μl) or 2 times a year (with a decrease in the number of CD4 + lymphocytes to 500 cells in 1 μl or less).

Brain research using CT or MRI is recommended to perform according to indications with a sharp decrease in the number of CD4 + lymphocytes (less than 200 cells per 1 μl).

Unplanned examinations should be performed if any signs of progression of HIV infection are detected or when associated diseases develop. According to the decision of the attending physician, additional studies are carried out.