HIV /AIDS

Notes

HIV epidemiology

 

 

  • Globally more than 35 million people are living with HIV/AIDS with the global incidence being estimated at 3 million.
  • In 2013, HIV prevalence in Kenya was estimated to be 6.0% with 1.6 million of people living with AIDS, of whom 191,840 were children.
  • In 2013 HIV incidence iln Kenya was 0.44% ;among the adults and it has been projected to stabilize at high rate of about 90,000 cases per year.
  • The HIV prevalence among voluntary donors in Kenya aws estimated at 2.6% in 2011 as compared with 7·4% of family replacement donors.
  • Key populations are defined as the groups who, due to specific higher risk behavior, are at increased risk of HIV, irrespective of the epidemic type or local context. They include: men who have sex with men (MSM); people who inject drugs (PWID) and sex workers (SW). In Kenya they contribute about 30% of new infections annually.
  • The World Health Organization (WHO) usually provides generic guidance on the treatment of HIV every 2-3 years for countries to adapt

 

Classification of HIV Virus

  • HIV-1 belongs to viral Group VI (ssRNA-RT), family of Retroviridae and genera of lentivirus.
  • There are two types of HIV, namely HIV-1 and HIV-2. Both viruses have similar morphology and lymphotropism, and the modes of transmission appear to be identical.
  • HIV-2 strains have been classified into at least five subtypes (A through E).
  • HIV 1 is more virulent and has shorter incubation period
  • The strains of HIV-1 can be classified into four groups: the "major" group M (more than 90% of all HIV) the "Outlier" group “O” and two new groups, N and P.
  • Group “O” distribution appears to be limited to West-Central Africa and group N strain, which was discovered in 1998 in Cameroon, is quite uncommon.
  • Group M is further divided into at least nine genetically distinct subtypes (or clades): A (predominant in West, Central Africa and Russia), B (predominant in Europe, the Americas, Japan and Australia), C (predominant in Southern and East Africa, India and Nepal, responsible for 50% of all global infections), D (predominant in East and Central Africa), F (predominant in Central Africa, South America and Eastern Europe), G (West and East Africa and Central Europe), H (Central Africa), J (Central America) and K (Democratic Republic of Congo and Cameroon).
  • Sometimes different HIV subtypes can be produced by recombination of genomic RNA to produce new hybrid virus. When an inter-subtype recombinant is transmitted between multiple individuals, i.e., has the potential to be of epidemiological significance, it is termed a Circulating Recombinant Form (CRF). As with the subtypes, these form distinct clusters in phylogenetic trees and some (CRF01 and 02 in particular) contribute disproportionately to the pandemic, as do certain subtypes (particularly C). Most recombinants though, do not mostly survive for long.
  • The HIV is characterized by high rates of genetic variability in vivo due to rapid viral turnover in a patient with an active disease (about 1010 viral particles per day) and lack of proof-reading mechanisms during reverse transcription that produces high mutation rates of about 10-4 mutations per nucleotide.
  • Approximately 50% of infected individuals in primary HIV infection are symptomatic with fever and lymphadenopathy.

 

HIV genome

  • The HIV genome is approlximately 9749 nucleotides long.The genome has various genes:

*The group-specific antigen gene (gag) codes for the gag polyprotein, which is processed during maturation to matrix protein (p17), capsid protein (p24), spacer peptide 1(p2), nucleocapsid protein (p7), spacer peptide 2 (p1) and p6.

*The Pol gene codes for viral enzymes reverse transcriptase, integrase, and HIV protease.

*The Env gene codes for gp160, the precursor to gp120 and gp41, proteins embedded in the viral envelope, which enable the virus to attach to and fuse with target cells.

*Transactivators include Trans-Activator of Transcription (tat), Regulator of Virion Expression (rev), Viral Protein R (vpr), viral infectivity factor (vif), Negative regulatory factor (nef) and Viral Protein U (vpu).

 

HIV replication

 

  • Successful HIV-1 replication requires the use of 3 enzymes: reverse transcriptase, integrase, and protease.
  • The viral gp120 binds to CD4 molecule on Th lymphocyte, macrophages, and/or microglial cells.
  • This triggers a conformational change on cell envelope allowing binding of the C-C chemokine receptor type 5 (CCR5 or CD195) or C-X-C chemokine receptor type 4 (CXCR-4, or fusin or CD184).
  • This further stabilizes the interaction and eventually the virus fusion protein (part of gp41) is uncovered.
  • The Env gp41 undergoes a conformational change and inserts itself into the membrane of the host cell to initiate the fusion of the two bilayers. This attachment and fusion process allows the HIV viral core to enter the host-cell.
  • Reverse transcriptase enzyme transcribes viral RNA into double-stranded DNA (dsDNA), which is then integrated, via the action of the integrase enzyme into the host-cell genome.
  • Integration of the linear provirus dsDNA into the genome of the host-cell establishes an infection that lasts for the lifespan of the cell, and all its progeny, which usually means life-long infection for the host.

 

HIV transmission

 

  • HIV is found in semen, vaginal or anal secretions, saliva, blood, wound exudates, breast milk and CSF.
  • HIV is transmitted through the following:

*Vaginal, anal or oral sexual intercourse

*Mother-to-child (MTCT) during pregnancy, labour, delivery and  breast-feeding.

*Blood transfusion

*Contaminated instruments such as needles (especially with IV drug users).

  • In 2012 in Kenya, 45% of married or cohabitating HIV infected persons had HIV-negative sexual partners (discordant couples). The HIV transmission among discordant couples could be as high as 10%-12% each year. The HIV negative partner should be re-tested 4 weeks after initial testing and then once a year.
Symptoms
  • Infection with HIV is followed by an acute flu-like illness that may remain unnoticed and it may not be associated with HIV infection.
  • This is followed by an asymptomatic carrier state, which progresses to clinical AIDS in about 50% of infected individuals within 10 years after seroconversion.
  • Seborrhoeic dermatitis especially on the scalp, central face.
  • HIV-associated pruritis.
  • Psoriasis
  • Kaposi’s sarcoma (neoplasm of vascular-forming cells that is characterized by bluish black nodules or plaque on the skin and mucus membrane)
  • Herpes simplex viral infections that are mostly chronic.
  • Herpes Zoster (80% of cases of Herpes zoster among the youth are HIV positive, and mainly at an early stage of it)
  • Molluscum contagiosum especially around the genitals.
  • WHO Clinical Staging Sytem of HIV/AIDS

*Patients are assigned to a given stage when they show one or more clinical conditions in that stage’s criteria.

*Stage 1.

**Asymptomatic patient

 **Persistent generalized

     lymphadenopathy

*Stage 2.

**Unexplained weight loss of less than

   10% of total body weight

**Recurrent respiratory infections

**Dermatological diseases e.g. herpes

    zoster flares, angular cheilitis,

    recurrent oral ulcerations, papular

    pruritic eruptions, seborrhoeic

    dermatitis, and fungal nail infections

*Stage 3.

**Weight loss of greater than 10%

**Persisntent diarrhea of unknown

    etiology

**Pulmonary tuberculosis

**Severe systemic bacterial infections

**Mucocutaneous conditions such as

    recurrent oral candidiasis

*Stage 4.

**All of the AIDS-defining illnesses.

**HIV wasting syndrome

**Pneumocystis pneumonia (PCP)

**Recurrent severe or radiological

    bacterial pneumonia

**Extrapulmonary tuberculosis

**HIV encephalopathy

**CNS toxoplasmosis

**Chronic or orolabial herpes simplex

    infection

**Esophageal candidiasis

**Kaposi’s sarcoma

**Cytomegaloviral (CMV) infections **Extrapulmonary cryptococcosis

**Disseminated endemic mycoses

**Cryptosporidiosis

**Isosporiasis

**Disseminated non-tuberculous

    mycobacteria infection

**Visceral herpes simplex infection

**Acquired HIV-associated rectal

    Fistula

**Cerebral or B cell non-Hodgkin

    Lymphoma

**Progressive multifocal

    leukoencephalopathy (PML)

**HIV-associated cardiomyopathy

    or nephropathy

Diagnosis
  • HTC services are guided by 5 core principles (5Cs) namely consent, confidentiality, counseling, correct results and connection-linkage to care and other appropriate post-test services.
  • The HIV test needs to be performed as per the approved National Testing Algorithm.
  • In Kenya, the Serial HIV Testing is used. After the initial testing the non-reactive specimen is concluded as a negative case; the reactive specimen is subjected to a Confirmatory test and if the specimen is reactive the case is concluded as positive; otherwise, if it is non-reactive the test is repeated in a HIV Comprehensive Care Clinic and tested using the National Testing Algorithm.
  • The universal HIV Testing Services (HTS) is classified into two main categories: Facility-Based HTCs and Community-Based HTCs. Each of the two settings is classified into Client-Initiated Testing and Counselling (CITC) and Provider-Initiated Testing and Counselling (PITC).
  • The Facility-Based CITCs are offered at integrated HTC sites while the PITCs within the facilities are offered at HTCs, integrated into routine OPD services, PMTCT, HTC in other clinics such as TB and MCH clinics as well as HTC offered in Medical Wards.
  • Community-Based CITCs are offered at HTC standalone units, Drop-in centers, workplaces and events as well as by self-testing and in the higher learning institutions. The PITCs within the community are offered on Index clients (where the homes of HIV-infected patients registered into care are identified, visited and household members tested for HIV) and on door-to-door testing by the providers.
  • DNA PCR (Early Infant Diagnosis, EID) should be conducted at 6 weeks or at first contact after 6 weeks. Infants aged 9-18 months can be tested using the Rapid HIV testing to establish possible exposure status. DNA PCR should be repeated at 18 months and/or when breastfeeding ends to provide the final infant diagnosis.
  • HIV Re-testing is to be done under the following condtions:

*Inconclusive results: Re-test after 2 wks

*General population: Re-test annually

*Those who test negative, repeat 3 months after.

*Key populations: Re-test quarterly

*Negative partner in discordant couples:Re-test at the initiation of ART for the HIV positive partner and then every 6 months

   *HIV negative pregnant women: Test in 1st trimester or first visit, 3rd trimester and 3 months post-delivery

   *Breast feeding mothers (low risk): Annual testing.

   *Breast feeding mothers (high risk) e.g. in case of discordant couples: after every 6 months.

 

  • For breast feeding mothers at high risk of infection e.g. those in discordant unions retest after every six months.
  • Persons who had a most recent (e.g. less than a month) specific exposure incidence; Test at initial presentation and re-test at 4 weeks, after which annual re-testing applies.
  • Symptomatic (STI, ) patients: Re-test after 4 weeks afterl initial test
  • All persons newly diagnosed as HIV positive: retest with a second specimen using the same testing algorithm at CCC, before enrollment into care initiation of ART (particularly pregnant or lactating women, children under 5, TB patients, KPs), to rule out potential misdiagnosis.
  • Disclosure of HIV status to the HIV infected child should be initiated from the age of 6 yrs and full disclosure should occur at the age of 10 yrs.
  • There is an increasing use of GeneXpert™, which can detect Mycobactrium tuberculosis DNA and rifampicin resistance from sputum specimen in less than 2 hrs.
  • Viral load is recommended under the following circumstances:

*All PLHIV at time of enrollment, after 6 months, after 12 months and then annually.

*All PLHIV with viral load of more than 1,000 copies/ml on routine viral load testing  need to be retested after 3 months following interventions.

*All PLHIV should be tested before making any single-ARV drug substitution in case the patient has been on ART for more than 6 months.

  • CD4 Count is recommended under the following circumstances:

*All PLHIV at time of enrollment (to determine the need for ART and also to determine the baseline Count.

*All PLHIV who are not on ART are to be tested 6-monthly to determine the qualification for ART.

*All PLHIV on ART who are on fluconazole prophylaxis to be tested 6-monthly to determine the need to continue with prophylaxis.

  • Other routine tests in PLHV:

* Lipid profile

* Liver function tests

* Renal function tests

* Hemogram

* Blood /urine sugar

* Serum amylase (for detection

   pancreatic disorder)

 

Management

## Interventions for primary prevention of HIV/AIDS include the following:

  • ABC of HIV prevention that include Abstinence (especially for the youth), Being faithful to one partner (and avoiding casual sex and sex with multiple partners) and

Codom (use and doing so properly).

  • Prompt treatment of STI
  • Counselling and Testing
  • Prevention g6g6 wq 1`of mother-to-child transmission (PMCT) during pregnancy, labour, delivery and breast-feeding from 15-45% to under 5% through:

*In the the WHO PMCT guideline (2015) the following is recommended:

**All pregnant and breastfeeding women living with HIV should be under treatment which should continued after delivery, during breastfeeding and  for life.

**All infants born to HIV-positive mothers should receive a course of antiretroviral treatment as follows:

Nevirapine OD orally for 4/52 at the

following dosage:

2mg/kg for those under 2kg;

10mg for those 2-2.5kg;

15mg for those who are more than 2.5mg.

When being breast-fed the infant should be

given Nevirapine OD x 6/52. When on

Replacement feeding: Nevirapine OD x      .                                 6/52

or  Zidovudine BD x 6/52.

 

*Proper breast feeding practices

  • Circumcision which is effective at preventing up to 60% of female-to-male transmissions
  • Vaccination with an efficacy of about 30%
  • Microbicide with an efficacy of about 39%
  • Physical barriers with effectiveness of up to 95% when used consistently
  • Pre-exposure prophylaxis (PrEP) with efficacy of up to 44% in Men having Sex with Men
  • Treatment with antiretrovirals (ART) can act as preventive measure too.
  • Post exposure prophylaxis (PEP) has demonstrated the rate of effectiveness higher than 80%
  • Effective screening of blood before transfusion.
  • Adequate measures to prevent HIV infection in a healthcare institution that include the following:

*Wearing of gloves and washing of hands whenever necessary.

*Proper decontamination of surfaces soiled with body fluids with appropriate decontaminants such as sodium hypochlorite 0.25%.

*Soaking of the instruments in glutaraldehyde solution.

*Soaking of linen /clothes in sodium hypochlorite solution before washing.

 

## Management of illness associated with HIV/AIDS including opportunistic infections (OIs)

 

Dx

Kaposi’s sarcoma

Rx

  1. ARVs (see the “ARV Regine”

For localized flat lesions:

  1. Vincristine 1.4mg/m2 monthly.

*For more extensive lesions

  1. Vincristine1.4mg/m2 + Bleomycin 10IU/m2 + doxorubicin 25mg/m2 monthly.

2nd Line: Paclitaxel alone or with doxorubicin

  1. Radiotherapy

……………………………………………………..

 

Dx

Herpes simplex viral (HSV) infections

Rx

  1. Tabs Aciclovir 200mg 5 times daily x 7-10 days [adult and children over 2 years]. Children under two years: ½ the above dose

………………………………………………

 

Dx

Pneumocystis jiroveci pneumonia (PCP)

Rx

  1. Tabs prednisolone 60mg daily tapered off over 3 wks
  2. IV Cotrimoxazole (TMP/SMX) 15mg TMP/kg/day QID or TID x 3/52

Or

  1. Tabs Cotrimoxazole Double Strength (960mg): 2 TID x 3/52.
  2. Tabs Dapsone 100mg OD x 3/52

………………………………………………..

 

Dx

Toxoplasmosis

(Treatment will take at least 6wks)

Rx

  1. Tabs Pyrimethamine 25-100mg OD
  2. Tabs Folic acid 10-20mg QID
  3. Tabs Sulphadiazine 1-1.5mg TID

Or

  1. Tabs Pyrimethamine 25-100mg OD 
  2. Tabs Folic acid 10-20mg QID
  3. Clindamycin 600-1200mg TID as infusion

Or

  1. Tabs Pyrimethamine 25-100mg OD
  2. Tabs Folic acid 10-20mg QID
  3. Tabs Azithromycin 1,200-1500mg OD

………………………………………………..…

Dx

Herpes Zoster

Rx

Aciclovir Tablet 800mg 5 times daily for 7 -10days

Or

Aciclovir I.V infusion 5mg/kg TID [over 1 hour]. Children: 3 mths - 12years; 250mg/m2 TID; upto 3months - 10mg/kg TID

Or

.Aciclovir topical application : Apply 5 times daily

…………………………………………..

Dx

Boils / furuncles

Rx

  1. Caps Cloxacillin 500mg QID X 2/52 

 Or

  1. Tabs Erythromycin 500mg QID X 2/52

 Or

  1. Cream Mupirocin local application upto TID 

…………………………………………….

Dx

Cryptococcal meningitis

Rx

  1. Inj Amphotericin B 0.7 -1mg daily

Or

  1. Caps Fluconazole 400mg daily for 6-10 wks then 200mg OD for life

……………………………………………

Dx

Orapharyngeal  candidiasis

Rx

  1. Inj Amphotericin B 0.7 -1mg daily

Or

  1. Caps Fluconazole 200mg STAT then 100mg OD x 2/52

Or

1.Tabs Ketoconazole 2-6mg/kg in  2 divided  doses  x 1/52

Or

  1. Miconazole oral gel apply BD and continue for at least a week after the symptoms have disappeared.

Or

Nystatin oral drops / cream apply QID (4-6) retaining in the mouth as long as possible before swallowing.

0r

  1. Gentian Violet apply TID

 

## Post-exposure Prophylaxis [PEP]

 

  • Provide HTS at the first contact.
  • Clinical evaluation, documentation and treatment of trauma.
  • Initiation of postexposure prophylaxis (PEP) within the shortest time possible but not later than 72 hours from the time of sexual assault. The HIV negative cases should be re-tested after 4 weeks and if still negative or in a discordant relationship re-test at 12 weeks.
  • Care after accidental neEDLe prick:

*Wash the skin thoroughly with the soap

*Squeeze the skin wound and allow the blood to flow.

*Apply an antiseptic with virucidal action such as surgical spirit, methylated spirit, betadine or iodine on the skin.

*For the eye rinse with clean water or eye wash.

*For the mouth or nose rinse with clean water and use a antiseptic if available.

*Then administer PEP

  • PEP regime:

*It involves taking a 28-day course of ARVs at normal treatment dose [with effectiveness of more than 80% with good compliance]

*For adults:

**Tenofovir (TDF) + lamivudine (3TC) + atanazavir/ritonavir (ATV/r).

*For children:

**Abacavir (ABC) + lamivudine (3TC) + Lopinavir/ ritonavir (LPV/r)

 

## Pre-exposure Prophylaxis [PrEP]

 

  • In 2015, the World Health Organization (WHO) issued guidelines for implementation of PrEP strategies
  • When taken consistently, PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92%.
  • In May 2017, the Government of Kenya launched a policy on HIV self-testing and PrEP to reduce HIV infection and initiated the implementation of the same.
  • In the HIV self-testing strategy, people are advised on where to get the testing kits and test themselves.
  • People who test negative for HIV are urged to discuss HIV prevention options that include PrEP
  • PrEP is offered free of charge in selected public health facilities (or at private hospitals and pharmacies at USD 36 a month) as part of a combination HIV prevention programme for people most at risk of HIV infection, who include:

_Serodiscordant couples

_People with multiple sexual partners

_individuals who have had sexually transmitted infections

_Intravenous drug users

_People who have had recurrent use of post-exposure prophylaxis (PEP)

_Sex workers

_Those who do not use condoms consistently

  • People at risk should be counselled to use safer sex and safer injecting practices in addition to PrEP
  • Currently, the medicine recommended for PrEP is a fixed-dose combination

_Tabs  tenofovir 300mg/emtricitabine 200mg (with the major brand being Truvada™) x  OD

_There should be a follow-up by a healthcare provider every 3 months.

 

## Chemotherapy of HIV/AIDS by Anti-retrovirals (ARVs)

 

  • Classification of ARVs

 

 

Generic Name

Trade name

Manufacturer

A.         Nucleoside analogues

1..Nucleoside reverse transcriptase

     inhibitors [NRTIs]

¤   

Abacavir, ABC

Ziagen®

GSK

¤   

Didanosine, ddl

Videx®

BMS

¤   

Emtricitabine, FTC

Emtriva®

Gilead

¤   

Lamivudine, 3TC

Epivir®

GSK

¤   

Tenofovir, TDF

Viread®

Gilead

¤   

Zalcitabine, ddC

Hivid®

Roche

¤   

Zidovudine, AZT

Retrovir®

GSK

2. Non-nucleoside reverse transcriptase in

     inhibitors [NNRTIs or NtRTIs]

¤   

Efavirenz, EFV

Sustiva®

DuPont

¤   

Delavirdine, DLV

Rescriptor®

Pharmacia

¤   

Nevirapine, NVP

Viramune®

Boerhinger

B. Protease Inhibitors  [PI]

¤   

Atazanavir, ATV

Reyataz®

BMS

¤   

Darunavir, DRV

Prezista®

Janssen

¤   

Fosamprenavir, FPV

Telzir®

GSK

¤   

Indinavir, IDV

Crixivan®

MSD

¤   

Lopinavir +

Ritonavir, LPV/r

[]

Kaletra®

Abbot

¤   

Ritonavir, RTV

Norvir®

Abbot

¤   

Nelfinavir, NFV

Viracept®

Roche

¤   

Saquinavir, SQV

Invirase®

Roche

C. Fusion Inhibitors [FI]

¤   

Enfuvirtide, T-20

Fuzeon®

Roche

¤   

Maraviroc, MVC

Selzentry®

Pfizer

D. Commercialized Fixed Dose Combinations (FDCs)

¤   

EFV

/FTC

/TDF

600mg

/200mg /

300mg

Atripla®

Cipla

¤   

3TC/NVP/AZT

150mg/

200mg/

300mg

Duovir-N®

Cipla

¤   

3TC/

AZT

150mg/

300mg

Combivir®

Duovir®

GSK

 

Cipla

           

 

 

Possible combinations in ARVs

 

 

NRTIs

NNRTIs

Protease

Inhibitors

Combinations of Choice

A

2 *

-

1+

B

2

1

-

C

2

 

1[plus RTV+]

Alternative Combinations

A

1

1

1

B

1

1

2 –low dose

C

-

-

2-full dose

D

2[plus ABV]

 

 

 

Mode of action of various ARVs

 

  • NRTIs: They are converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.
  • NNRTIs: They inhibit viral reverse transcriptase and viral DNA synthesis.
  • PIs: Inhibits HIV proteases, preventing viral maturation and replication.
  • Fusion blockers: They bind to viral glycoprotein subunit gp41 and hence block viral fusion with CD4 receptor of the host cells and thus viral entry to the cell e.g.

 

  • Nucleotide analogues: Their metabolites inhibit viral polymerase and terminates the the DNA chain when incorporated into viral DNA e.g. tenofovir.

 

  • Recommended ART Regimes

 

Age

(yrs)

First choice and first line

Alternative

choice, first line

Second line

≤ 3

ABC + 3TC +LPV/r

AZT + 3TC +

LPV/r

AZT+ 3TC + DRV/r

≤ 3 (HIV co-infection with TB)

 

ABC + 3TC + LPV/r + RTV (to make the LPV/RTV ratio 1:1 )

AZT + 3TC +LPV/r

 

ABC + 3TC + EFV

 

AZT + 3TC + EFV

 

ABC + 3TC + AZT (last option)

 

≥3-10yrs and

< 35kg

ABC+3TC + EFV

ABC+3TC+ VP   

AZT + 3TC + LPV/r*

 

AZT/D4T+ 3TC + EFV / NVP 

ABC + 3TC + LPV/r

≥3-10yrs and

< 35kg (HIV co-infection with TB)

ABC+3TC + EFV

AZT+3TC+ EFV

 

>10-14 yrs) and weight ≥ 35 kg

TDF+3TC+ EFV

TDF + 3TC + NVP

 

ABC + 3TC+ EFV/NVP

 

AZT + 3TC + EFV/NVP

AZT+3TC+LPV/r

 

Or less preferred

 

AZT+3TC+ATV/r

>10-14 yrs) (HIV co-infection with TB)

For <35 kgs: ABC+ 3TC +EFV

 

For >35 kgs:TDF + 3TC + EFV

AZT + 3TC + EFV

 

Adolescents (≥15 yrs) and Adults, discordant couples, pregnant and breastfeeding women

TDF+3TC + EFV

TDF+3TC+

NVP

 

 

 

 

 

AZT + 3TC + ATV/r or LPV/r

AZT/D4T + 3TC+ EFV/NVP

TDF+ 3TC+

LPV/r

All women with previous exposure to NVP through PMTCT less than 2yrs since NVP exposure

TDF + 3TC + ATV/r

TDF + 3TC + LPV/r

 

AZT + 3TC + ATV/r

 

AZT + 3TC + LPV/r

AZT + 3TC+

DRV/r

All women with previous exposure to NVP through PMTCT less more than 2yrs since NVP exposure

(as per the adults above)

 

TDF + 3TC + ATV/r

 

 

PEP Regime for 28 days

TDF+3TC + ATV/r (adults)

 

ABC +3TC + ATV/r (Children)

 

 

 

 

NB:

*A viral load test need to be conducted before any drug substitution to rule out treatment failure.

*In case where the patient aged 0-10 yrs develops TB while on ARVs change to the regime of “HIV co-infection with TB” but where NVP is being used replace with EFV.

*Triple nucleoside is an inferior regimen and should only be used in children not able to tolerate super boosted LPV/r (LPV: RTV of 1:1).

*Switch back to LPV/r-based regimen after completion of TB treatment

*For patients with pre-existing renal disease TDF is substituted by ABC  which does not need dose adjustment.

 

 

Summary of adverse effects of ARVs

 

1. Lipodystrophy

¤ Include: Peripheral lipoatrophy, central fat accumulation

¤ NRTIs and PIs

[Mostly NRTIs; very common with d4T]

2. Metabolic abnormalities

a]Dyslipidaemia

¤ Advisable to monitor blood lipid levels in patients on PIs and NNRTIs]

¤ PIs [increase LDL, triglyceride and total cholesterol]

¤ NNRTIs

[increase plasma LDL and HDL]

b]Hyperglycaemia and Insulin resistance

¤ Diabetes and DKA can develop

¤ Monitor glucose levels

¤ Mostly with PIs

¤ It can be reversible

c]Lactic acidaemia

¤ Mostly with NRTIs and NtRTIs

[common with d4T but more serious with d4T and ddI].   

3. Cardiovascular diseases

¤ Risk increased by the above factors

4.Hepatotoxicity

¤ NNRTIs [Mostly with NVP where it causes hepatitis]

¤ PI [common with Ritonavir]NRTIs [though it occur rarely they can cause lactic acidosis and hepatomegally that can be dangerous – more likely with AZT, d4T and ddI]

5. Rashes

¤ Mostly with NNRTIs especially NVP, less likely with PIs [though common with amprenavir] and NRTIs [ though common with Abacavir]

¤ They can be expressed to serious diseases as Steven-Johnson syndrome or toxic epidermal necrosis.

¤ These rashes are unresponsive to antihistamines and corticosteroids.

6. Bone changes

¤ Reduced bone density [mainly associated with PIs]

 

 

 

 

     When to commence the antiretroviral

      therapy in adolescents and adults:

 

  • All HIV-infected adolescents and adults with CD4 count <500 cells/mm3 irrespective of WHO stage
  • All HIV-infected pregnant women irrespective of CD4 count, WHO stage or gestation age
  • All HIV-infected breastfeeding women irrespective of CD4 count, WHO stage
  • All HIV-infected spouses and sexual partners in sero-discordant relationships irrespece of their WHO stage or CD4 cell count
  • All HIV-infected adolescents and adults with WHO stage 3 and 4 disease irrespective of CD4 count
  • All Hepatitis B Virus/HIV co-infected persons irrespective of CD4 coun
  • All TB/HIV co-infected persons irrespective of CD4 count

 

 

 

  • ARV Prophylaxis for HIV-Exposed Infants

 

*Scenerio of exposure:

Scenerio 1:The mother diagnosed as HIV positive during gestation or after birth. Initiate infant HIV prophylaxis with NVP and maternal ART.

Scenerio 2: Infant identified as HIV exposed after birth and breast-feeding. Initiate infant HIV prophylaxis with NVP and maternal ART.

Scenerio 3: Infant identified as HIV exposed after birth and NOT breast-feeding. No drug and maternal ART.

Scenerio 4: Mother  interrupts ART regimen when breastfeeding. Initiate infant HIV prophylaxis with NVP

 

*After initiating NVP prophylaxis EID should be conducted at 6 weeks or at first contact after 6 weeks and then progress as per the stipulated guidelines. If the results are positive ART is initiated otherwise if they are negative NVP prophylaxis is continued up to 12 weeks.

 

  • Nevirapine dosing for HIV Exposed Infants

 

NB: NVP comes in suspension of  50mg/5mL

 

The dose is given once daily as follows: 0 - 6 wks and birth weight < 2500g - 10mg (1mL); 0- 6wks and birth weight > 2500 g - 15mg (1.5 mL); 6-14wks: 20mg (2mL); 14 wks-6 months: 25mg (2.5 mL); 6 - 9 months: 30mg (3 mL); 9 - 12 months: 40 mg (4mL); > 12 months: 50mg (5mL)

  • Cotrimoxazole prophylaxis in the HIV exposed patient

 

*Co-trimoxazole prophylaxis is the standard of care for preventing Pneumocystis jiroveci pneumonia (PCP) (formerly Pneumocystis carinii pneumonia) and toxoplasmosis.

*All HIV infected patients and HIV-exposed infants born to mothers living with HIV require co-trimoxazole prophylaxis,

* HIV-exposed infants born to mothers living with HIV  require this prophylaxis from 4–6 wks of age (or at first encounter with health care system) and continued until HIV infection can be excluded.

*Dose of cotrimoxazole prophylaxis in the HIV exposed patient:

**The dose is given once per day.

** The common strength of suspension is 240mg/5ml (equivalent to ½ of the single strength tablet or ¼ of the double strength tablet).

**Dose (based on weight):

1 to 4 kg - 2.5mL; 5 to 8kg -5mL;  9 to 16 kg -10mL; 17 to 30: 15mL;  > 30kg – 20mL

 

Isoniazid Preventive Therapy [IPT]

Criteria for administration of IPT

  • HIV-infected children less than 12 months of age who have had recent contact with active TB disease with no evidence of TB
  • All PLHIV above 12 months of age who screen negative for TB using the ICF tool
  • All children under 5 years irrespective of HIV status who had recent close contact (past 12 months) of smear positive TB case
  • Prisoners, irrespective of HIV status
  • Dose: 10 mg/kg/day (maximum 300 mg) for 6 months: <5: 50mg [0.5 tab], 5.1 to 9.9:100mg [1 tab],10 to13.9:150mg [1.5 tabs], 14 to19.9:200mg [2 tabs], 20 to 24.9:250mg [2.5], >25: 300mg [3 tabs], adults: 300mg [3 tabs]
  • Isoniazid must be co-administered with the daily dose of pyridoxine to reduce the risk of peripheral neuropathy in the following dose based on weight: 5 to 7yrs - 12.5mg (1/4 tabs), 8 to14 yrs – 25mg (1/2); ≥ 15 yrs – 50mg (1 tab).
  • Additional pharmacology of Isoniazid

*Mode of Action: Isoniazid interferes with lipid and nucleic acid biosynthesis in growing organisms.

*Precautions:Hepatic and renal impairment.

*Contraindications: Epileptic convulsions; chronic alcoholism; symptoms  of peripheral neuropathy; acute hepatitis.

*Side effects: GI disturbances, vertigo, drowsiness, headache, peripheral neuritis, xerostoma, visual disturbances, tinnitus and hypersensitivity reactions.

*Pregnancy risk category: A.

 

## Other types of interventions

  • Counselling of patients or clients
  • Encourage consumption of balanced diet
  • Encourage the social support system through the family, HIV-peer group and community involvement

 

## Specific pharmacology of ARVs

 

 

    Abacavir, ABC

Indications: HIV infection in combination with other ARVs.

Mode of action: Nucleoside reverse transcriptase inhibitors [NRTIs] that are converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.

Precautions: Hepatic impairment; patients weighing less than 40kg should not be given ABC in fixed combination with AZT and 3TC; reduce dose in cases or renal impairment.

Contraindications: Pregnancy and breastfeeding.

Side effects: Serious allergic reactions [stop treatment and do not rechallenge], GI disturbances, fever, headache, fatigue, lactic acidosis.

Pregnancy risk category: C.

Dose: HIV infection in combination with other antiretroviral drugs: 600 mg daily in 1–2 divided doses; Child 3months-12 years, 8mg/kg [max. 300 mg] twice daily or 16 mg/kg [max. 600 mg] once daily or Body-weight 14-21 kg, 150 mg twice daily or 300 mg once daily; Body-weight 21-30 kg, 150 mg in the morning and 300 mg in the evening or 450 mg once daily; Body-weight over 30 kg, 300 mg twice daily or 600 mg once daily, Child 12–18 years, 300 mg twice daily or 600 mg once daily.

 

     Atazanavir, ATV

Indications: HIV; used in combination with other ARVs.

Mode of action: Protease inhibitors [PI] Inhibits HIV proteases, preventing viral maturation and replication.

Precautions: Proton pump inhibitors[PPIs] may reduce its absorption as it is best absorbed in acidic media; since it causes hyperbilirubineamia it has the potential of causing kernicterus in neonates.

Contraindications: Severe hepatic dysfunction, absorption affected markEDLy by antacids.

Side effects: Hyperbilirubineamia that causes reversible jaundice; dizziness; fatigue; depression; abdominal pain; rash; heart block; acidosis and hepatitis.

Dose: HIV infection in combination with other antiretroviral drugs:With low-dose ritonavir, 300 mg once daily;Child 6–18 years;Body-weight 15–20 kg, 150 mg once daily; Body-weight 20–40 kg, 200 mg once daily; Body-weight over 40 kg, 300 mg once daily. When combined with ritonavir, efavirenz or tenofovir the daily dose can be reduced to 300mg OD.

                       

    Atazanavir/ritonavir (ATV/r)

Indications: HIV; used in combination with other ARVs. It is also safe in pregnancy.

Mode of action: Protease inhibitors [PI] Inhibits HIV proteases, preventing viral maturation and replication.

Precautions: Proton pump inhibitors [PPIs] and other antacids may reduce its absorption as it is best absorbed in acidic media (LPV/r is prescribed instead) ; since it causes hyperbilirubineamia it has the potential of causing kernicterus in neonates. The use ATV/r with rifampicin leads to the reduced blood levels of ATV/r hence in TB/HIV co-infected patient on ATV/r, Rifampicin must be replaced with Rifabutin 150mg OD.

Contraindications: Severe hepatic dysfunction, absorption affected markEDLy by antacids. Children aged less than 6 yrs.

Side effects: Hyperbilirubineamia that causes reversible jaundice; dizziness; fatigue; depression; abdominal pain; rash; heart block; acidosis and hepatitis. [ATV/r  is better tolerated than LPV/r partly due to the reduced ritonavir that is used]

Dose:  The tablet is taken once daily.

In the EDL only the tablets for those  ≥40 kg (ATV 300mg + RTV 100mg) are available and it should not be crushed.  Others dosages are:

15 to <20 kg: ATV 150mg + RTV 100mg

 20 to <40 kg: ATV 200mg + RTV 100mg.

It must be taken with food to enhance absorption.

 

     Didanosine, ddl

Indications: HIV in adults and children over three months with progressive or advance immuno-deficiency. Used in combination with other ARVs.Mode of Action: Nucleoside reverse transcriptase inhibitors [NRTIs] that are converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.

Precautions: Hyperuricaemia, peripheral neuritis, sodium restriction diet, phenylketonuria, monitor complete blood count, differential count, aminotransferases, K+, amylase and triglycerides bimonthly.

Contraindications: Pregnancy and lactation, severe renal and hepatic dysfunction.

Drug interactions: Quinolones and tetracyclines reduce its effect; pentamidine enhances its pancreatitis side effects.

Side effects: GI disturbances diarrhoea, pancreatitis, peripheral neuropathy, dry mouth and taste disturbances, hepatitis, CNS disturbances, alopecia, diabetes mellitus and insipidus.

Pregnancy risk category: B2.

Dose: 125-200mg orally BD or 400mg OD.

 

     Darunavir, DRV

Indications: HIV infection in combination with other ARVs.

Mode of Action: Protease inhibitors [PI] Inhibits HIV proteases, preventing viral maturation and replication

Precautions: To use together with ritonavir

Contraindications: Hypersensitivity to the components of the formulation; contraindication to ritonavir

Side Effects: Raised hepatic and pancreatic enzymes, hypertriglyceridaemia, diarrhoea, hypercholesterolaemia, headache, abdominal pain and vomiting.

Special Information: Ritonavir [100 mg twice daily] is used as a pharmacokinetic enhancer

Pregnancy Risk Category: C

Dosage: Aduls: 600 mg BD taken with ritonavir 100 mg BD and with food.

 

     Efavirenz, EFV

Indications: HIV in combination with other ARVs.

Mode of action: Non-nucleoside reverse transcriptase inhibitors [NNRTIs or NtRTIs] that inhibit viral reverse transcriptase and viral DNA synthesis

Precautions: Reduce dose in serious hepatic disorders; higher risks of worsening of psychiatric disorders.

Contraindications: Cisapride; ergot alkaloids; triazolam and midazolam. Avoid use in children less 3 years.

Side effects: Neurological disturbances [common] such as dizziness, drowsiness and impaired concentration; rashes especially in children; hypocholesterolaemia; allergic reaction; suicidal tendency; seizures; erythema multiforme; Steven-Johnson; tachycardia.

Dose: 600mg OD.

Dose in children:

3-17yrs [capsule or tablet]

 

Weight [kg]

Dose:

[mg once daily]

13- <15

200

15- <20

250

20- <25

300

25- <32.5

350

32.5- < 40

400

40 >

600

 

3-4 yrs [oral liquid]

 

Weight [kg]

Dose:

[mg once daily]

13- <15

360

15- <20

390

20- <25

450

25- <32.5

510

 

5-17 yrs [oral liquid]

 

Weight [kg]

Dose:

[mg once daily]

13- <15

270

15- <20

300

20- <25

360

25- <32.5

450

32.5- < 40

510

40 >

720

*In children:

3.5 - 4.9 kg:    100mg              [≡ ½ 200mg   tab]

5 - 7.4 kg:                      150mg [≡ ¾ 200mg   tab]

7.5-13.9kg:      200mg [≡ 1 200mg    tab]

14-19.9kg:                     300mg [≡ 1½ 200mg tab]

20 - 24.9kg:     300mg             [≡ 1½ 200mg tab]

25 - 34.9kg:    500mg              [≡ 2 200mg    tab]

35 and above: 600mg              [≡ 1 600mg    tab]

 

     Emtricitabine, FTC

Indications: HIV & HBV infections.

Mode of action: Nucleoside reverse transcriptase inhibitors [NRTIs] that are converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.

Precautions: Decreased dose in case of renal impairment; to watch out on the possibility of rebound of hepatitis B infection after stopping treatment in case of HIV/hepatitis B coinfections.

Contraindications: Children below 4 years; no safety data is currently available.

Side effects: Rash; diarrhoea; cough; hyperpigmentation of palm or/and sole especially in women.

 

    Indinavir, IDV

Indications: HIV infection.

Mode of action: Protease inhibitors [PI] inhibits HIV proteases, preventing viral maturation and replication.

Precautions: Monitoring of aminotranferases, bilirubin level, cholesterol and triglycerides, on bi-monthly basis; increased risk of nephrolithiasis in case of dehydration; reduce dose in case of marked liver impairment; blood concentration is reduced in the 3rd trimester of pregnancy. 

Contraindications: Acute porphyria, hypersensitivity reactions, alprazolam, alfuzosin, amiodarone, rifampicin and sildenafil.

Side effects: Common side effect is nephrolithiasis [kidney stones] which is more likely in children; unconjugated hyperbilirubinaemia; malaise; flank pain; back pain; abdominal pain; alopecia; ingrown toe nails; dried cracked skin [‘retinoid syndrome’]; vasculitis; oedema; haemolytic anaemia and hepatitis.

Pregnancy risk category: B3.

Dose: 800mg orally TID

 

    Lamivudine [3TC]

Indications: HIV infection [in combination with other anti-retrovirals]; chronic hepatitis B viral infection after evidence of replication [positive PCR test results].

Mode of action: A nucleoside reverse transcriptase inhibitor [NRTIs] that is converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.

Precautions: If creatinine clearance is below 50mL/minute reduce the dose and do not use the drug in combination with any other ARVs; to watch out on the possibility of rebound of hepatitis B infection after stopping treatment in case of HIV/ hepatitis B co-infections. In advanced disease, combination with AZT is prone to produce serious anaemia at the begining of treatment hence complete blood count is done initially and repeated at 3-month intervals.

Contraindications: Combination with zalcitabine; for patients weighing less than 40kg the fixed combination with abacavir and AZT is avoided and instead each drug is used separately.

Side effects: Peripheral neuropathy, rashes, diarrhoea; fatigue; anaemia; neutropenia; thrombocytopenia; fever; rash; raised liver enzymes.

Pregnancy risk category: B3.

Dose: HIV: Children above 12yrs and adults; 150mg BD or 300mg OD. For children 0.25-12yrs; 4mg/kg BD [max.300mg daily]. [the drug is taken on an empty stomach]. HBV: Children above 12yrs and adults; 100mg OD. For children 2-11yrs; 3mg/kg OD [max. 100mg daily]. HIV/HBV co-infection: 150mg BD.

 

     Lopinavir /Ritonavir , LPV/r

Also see the details under ritonavir and lopinavir.

Indications: HIV infection.

Precautions: Monitoring of aminotranferases, triglycerides, CK and uric acid preferably on bi-monthly basis.

Side effects: Common S/E’s are GI distress and peripheral paresthesias.

Additional labeling: B.

  • Ritonavir super-boosting for TB/HIV co-infection

*In children:

Formulation A: 80mg Lopinavir/ 20mg ritonavir per ml solution.

Formulation B: 200mg Lopinavir/ 50mg ritonavir Tablets

Formulation C: Ritonavir liquid (80mg/ml)

Formulation D: Ritonavir capsule 100mg

 

The Dose is given TWICE daily:

3.5 - 4.9   kg:   1.5mL A + 1mL    C

5    - 7.4   kg:   1.5mL A + 1mL    C     

7.5 - 13.9 kg:   2.0mL A + 1.5mL C       

14-19.9    kg:   2.5mL A + 2mL    C or

                              1 tab B   +  2 Caps D

20  -24.9  kg:   3mL A   +  2.5mL C  or

                              1 tab B   +  2 Caps   D

The dose is split as follows:

25 - 34.9kg:     4mL A   +  4mL AM and                                                    2PM  C  or

                              2 tab AM and 1 tab                                                            PM B   +  2 caps  AM and                                                 3 Caps PM D

 

     Nelfinavir, NVF

Indications: HIV [in combination with other ARVs].

Mode of action:  A protease inhibitor [PI] inhibits HIV proteases, preventing viral maturation and replication.

Precautions: Monitoring of cholesterol and triglycerides; drug blood concentration decreases in pregnancy, hence a need for monitoring plasma concentration with intent of adjusting the dose accordingly.

Contraindications: Amiodarone; quinidine.

Side effects: Most common: diarrhoea. Others: abdominal pains; flatulence; rash; hypersensitivity; fatigue; hepatitis; pacreatitis; oral ulcers and nephrolithiasis.

Pregnancy risk category: B2.

Dose: Adult: 750mg TID or 1250mg BD. Children 2-13 yrs: 25-30mg/kg TID [max. 750mg]. [Taken with meals for best absorption]

 

     Nevirapine, NVP

Indications: HIV [in combination with other ARVs]; very useful in prevention of vertical transmission of HIV in the late pregnancy.

Mode of action: A non-nucleoside reverse transcriptase inhibitor [NNRTI or NtRTI] that inhibits viral reverse transcriptase and viral DNA synthesis

Precautions: It is rarely affected by the status of renal functions hence there may not be any need of changing the dosage in case of renal impairement unless the creatinine clearance is below 20mlL/minute; paradoxically probability of hepatoxicity increases with the increase of CD4 counts, with more pronounced effect in women. Rifampicin reduces its plasma concentration. Known to cause serious dermatological reactions in children.

Contraindications: Severe hepatic disorders [with AST or ALT levels of more than 5 times of the normal levels].

Side effects: The most common side effects are rashes and body weakness. Others include: hypersensitivity reactions; serious fulminant hepatitis; Steven-Johnson syndrome; anaemia; granulocytopenia and arthralgia.

Pregnancy risk category: B3.

Dose: Adults: 200mg OD x 2/52 then 200mg BD. Children: 2 months to 7 years; 4mg/kg OD x 2/52 then 7mg/kg BD [max. 400mg/day]. 8 to 16 yrs; 4mg/kg OD x 2/52 then 7mg/kg BD [max. 400mg/day]

The incidence for rash is reduced if introduced at a low dose and dose increased after 14 days.

 

 

    Raltegravir, RAL

Indications: HIV infection in combination with other ARVs

Mode of Action: An integrase inhibitor that targets a viral enzyme that catalyses the insertion of HIV-1 proviral DNA into the host’s cellular genome

Precautions: Possibility of allergic reaction

Contraindications: Allergy to the drug or any other component of the product

Side Effects: Insomnia; fatigue; headache; nausea; diziness; allergic reactions.

Pregnancy Risk Category: C

Dosage: Adults and those above 12yrs: 400mg BD [800mg if given with rifampicin]. 6 to 12yrs at least 25kg: 400mg BD. 6 to 12yrs below 25kg: weight based upto 300mg BD. 2 to 6yrs at least 1kg: weight based upto 300mg BD.

 

     Ritonavir, RTV

Indications: HIV [in combination with other ARVs].

Mode of action:  A protease inhibitor [PI] inhibits HIV proteases, preventing viral maturation and replication.

Precautions: Monitoring of aminotranferases, triglycerides, CK and uric acid preferably on bi-monthly basis.

Contraindications: Amiodarone; quinidine; diazepam; dexpropoxyphene; piroxicam; pethidine; zolpidem; clozapine and bupropion. Concomittant use with saquinavir and rifampicin can cause hepatitis.

Side effects: Common include: GI distress, peripheral paresthesias and hepatotoxicity. Others are: taste disturbance; dizziness; dysuria; sweating; vasodilation and palpitations. 

Additional labeling: B.

Dose: 600mg orally BD. Taken with meals.

 

     Saquinavir, SQV

Indications: HIV [in combination with other ARVs]. It is infrequently used as a sole PI due to its poor absorption profile.

Mode of action: Protease inhibitor.

Precautions: Monitoring of aminotranferases, cholesterol and triglycerides preferably on bi-monthly basis; it is metabolized in the liver hence its dose reduced in serious hepatic impairment.

Contraindications: Predisposition to cardiac arrhythmias [including congenital QT prolongation, bradycardia, history of symptomatic arrhythmias, heart failure with reduced left ventricular ejection fraction, electrolyte disturbances, concomitant use of drugs that prolong QT or PR interval]; concomitant use of drugs that increase plasma-saquinavir concentration [avoid unless no alternative treatment available], efavirenz; rifampicin and amiodarone.

Side effects: Abdominal pain; flatulence; dry eyes; cough; oral ulcers and general weakness.

Pregnancy risk category: B1.

Dose: 600mg TID. Taken with food.

 

    Tenofovir / Lamivudine, TDF + 3TC

(Tabs,  300mg/300mg)

For precautions, contraindications and side effects see TDF and 3TC respectively.

Indications: HIV infection.

Additional labeling: 12.

Dose: 1 tablet once daily.

 

 

   Tenofovir /Lamivudine / Efavirenz,

    TDF + 3TC + EFV

(300mg/300mg/600mg)

For precautions, contraindications and side effects see TDF, 3TC and EFV respectively.

Indications: HIV infection.

Dose: 1 tablet once daily.

 

    Telbivudine

Indications: Chronic hepatitis B infection

Mode of Action: It is a synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. [It is phosphorylated by cellular kinases to the active triphosphate which involves competition with the natural substrate thymidine 5'-triphosphate and incorporation into viral DNA, causing DNA chain termination form].

Precautions: Hepatic function must be monitored.

Contraindication: Hypersensitivity to the active substance or to any of the excipients.

Side effects: Musculoskeletal, connective tissue and bone disorders rhabdomyolysis has been very rarely reported.

Special Information: It is the unmodified β-L enantiomer of naturally-occurring thymidine.

Dose:  600mg OD [for adult only]

 

     Tenofovir, TDF

Indications: HIV with other ARVs.

Mode of action: A reverse transcriptase inhibitor.

Precautions: Level of didanosine is raised when used with tenofovir hence it should be given at least 2hr before or 1hr after taking ddI. Tenofovir level is raised by antivirals acyclovir, ganciclovir and valaganciclovir.

Contraindications: Lactic acidosis; allergy.

Side effects: Headache; nausea, flatulence, anorexia, diarrhoea, abdominal; renal dysfunction and change in fat distribution.

Dose:  300mg depending creatinine clearance [CCr]. For CCr 30-49ml/min: 300mg after every 48hrs. For CCr 10-29ml/min: 300mg twice a week. For CCr less than 10ml/min do not use tenofovir. Taken with meal

 

     Tenofovir / Emtricitabine,

     TDF + FTC

For precautions, contraindications and side effects see TDF and FTC respectively.

Indications: HIV infection.

Dose: 1 tablet once daily.

 

    Tenofovir / Emtricitabine/ Efavirenz,

    TDF + FTC + EFV

(300mg/200mg/600mg)

Also see the details under TDF, FTC and EFV respectively.

Indications: HIV infection.

Dose: 1 tablet once daily.

 

    Zidovudine, AZT

Indications: HIV in adults and children with progressive or advance immunodeficiency. [T-helper cell counts of less than 500/mm3]. Used in combination with other ARVs.

Mode of Action: Nucleoside reverse transcriptase inhibitors [NRTIs] that are converted by cellular cells’ enzymes to active phosporylated metabolites that inhibit viral reverse transcriptase and viral DNA synthesis.

Precautions: Hepatic and renal impairment, 1st trimester of pregnancy, avoid in lactation, monitor haematological parameters.

Drug interactions: HB of less than 7.5g/dl, neutrophil counts of less than 0.75x109 /L.

Side effects: Anaemia [sometimes fever], haematological disorders like neutropenia, malaise, nausea, vomiting, anorexia, headache, insomnia, abdominal pains, myalgia.

Pregnancy risk category: B3.

Dose: Asymptomatic disease - initially 500mg to be increased as the disease progresses to 1.5g daily. Symptomatic disease 200mg every 4hrs. If tolerance is poor - 100mg every six hours. Children over 3months -180mg/m2 every 6hrs. I.V inf. - 2.5mg/kg every 4 hrs [for less than 2 weeks.

 

    Zidovudine / Lamivudine, AZT + 3TC

(150mg/300mg)

For precautions, contraindications and side effects see AZT  and 3TC respectively.

Indications: HIV infection.

Dose: 1 tab BD

 

    Zidovudine /Lamivudine / Abacavir, AZT + 3TC + ABC

(300mg +300mg + 150mg)

For precautions, contraindications and side effects see ABC, 3TC and AZT respectively

Indications: HIV infection.

Dose: I tab BD

 

     Zidovudine / Lamivudine/ Nevirapine

AZT + 3TC + NVP

(150mg/300mg/200mg)

Also see the details under AZT, NVP and 3TC respectively.

Dose: 1 tab BD

Drug Index 2.0 is here
Our new update features a more powerful search feature and easier login. Having any issues? Contact us today. Contact Us