ADDENDUM TO THE 2016 GUIDELINES FOR ANTIRETROVIRAL THERAPY FOR

THE PREVENTION AND TREATMENT OF HIV IN ZIMBABWE 

29^th March, 2019 

The National Medicines and Therapeutics Policy Advisory Committee (NMTPAC) and AIDS and TB Directorate of the Ministry of Health and Child Care wishes to update the 2016 ARV Guidelines based on recent advances in HIV Treatment and the Management of Latent TB Infection. In 2018, WHO released a Policy Brief with updated recommendations on First Line, Second Line ART and Post-Exposure Prophylaxis (PEP) together with the 2018 WHO Guidelines on the Management of Latent TB Infection.

This Addendum is organized in the following four main sections: 

1. First- Line, Second- Line and Third-Line ARV Regimens for Adults and Adolescents; 
2. First- Line, Second- Line and Third-Line ARV Regimens for Children;
3. Dolutegravir Use in HIV Post-Exposure Prophylaxis, 
4. Management of Latent TB Infections. 

Each section provides guidance to the clinical and/or management recommendations followed by main considerations for adopting the recommendations in Zimbabwe. 

I.First- Line, Second- Line and Third-Line ARV Regimens for Adults and Adolescents 

 First Line ARV Regimens for Adults and Adolescents

Adult men, adolescent boys and women not of childbearing potential, women of childbearing potential with effective contraception*including pregnant women after the first trimester.

First Line- Tenofovir/Lamivudine/Dolutegravir

Alternative- TAF**/Emtricitabine/Dolutegravir, Tenofovir/Lamivudine/Efavirenz 400, Tenofovir/Lamivudine/Efavirenz 600

Women of childbearing potential who have no effective contraception including pregnant women in the first trimester.

First Line-Tenofovir/Lamivudine/Efavirenz400/600

Alternative- Zidovudine/Lamivudine/Efavirenz 600 OR Abacavir/Lamividine/ Efavirenz 600 OR  Zidovudine/Lamivudine/Efavirenz 600

• TLD may be used for adolescents weighing over 30 kg
• *Effective contraception is defined as correct use of the following methods: Contraceptive intrauterine device (IUD) or intrauterine system (IUS); Subdermal contraceptive implant or Progestogen injections. Male or female condom use is recommended with all contraceptive methods for dual protection against pregnancy and to avoid transmission of HIV and other sexually transmitted infections.
• **TAF is Tenofovir alafenamide and can be used as a substitute for TDF.  Avoid giving TAF in pregnancy and HIV/TB patients on Rifampicin. Further guidance of its use will be provided by the programme when it becomes more readily available on the market.
• ***Use of TLE400 in women and adolescent girls of child bearing potential with no effective contraception who are not pregnant while TLE600 is used for those pregnant in first trimester

Main Considerations  

• Dolutegravir (DTG) is a safe and efficacious drug with a rapid viral suppression, low potential for drug-drug interactions and a high genetic barrier to developing ARV drug resistance. It should be given as a preferred first line regimen for ART naïve patients.
• Exposure to DTG at the time of conception may be associated with an increased risk of neural tube defects among infants. DTG should not be given to HIV infected pregnant women during their first trimester. 
• Adolescent girls and women of childbearing potential:
  • • Should be given adequate information to make informed choices about their treatment options. 
    • Who do not currently want to become pregnant and women who are breastfeeding SHOULD be offered a pregnancy test first before receiving the preferred regimen containing DTG together with documented evidence of a reliable long-term contraceptive method i.e. contraceptive intrauterine device (IUD) or intrauterine system (IUS); subdermal contraceptive implant or progestogen injections 
    • Women on DTG who plan to get pregnant should discuss with their health care provider for provision of alternative antiretroviral treatment 

• Regarding pregnancy:
  • An EFV-based regimen is a safe and effective first-line regimen recommended for use by women of childbearing potential who desire to get pregnant or who have no effective contraception i.e. Tenofovir/ Lamivudine/Efavirenz 400
  • If pregnancy is identified in the first trimester (up to 12/40 gestation), women should switch to Tenofovir/ Lamivudine/Efavirenz 600 
  • Once a pregnancy is 12/40 and over, women should switch to Tenofovir/Lamivudine/ Dolutegravir (TLD) and continue that regimen while breastfeeding with provision of effective contraception
• ART experienced patients should be transitioned to a DTG-containing regimen after confirming a suppressed HIV viral load of <1,000 copies/ml in the past twelve months. If the VL is not suppressed, manage as treatment failure. 
• In PLHIV with TB using rifampicin, the dose of DTG should be increased to 50 mg twice daily.
• Use of Nevirapine (NVP) in adults and adolescents is being phased out and health providers are advised to limit its use 
• Tenofovir alafenamide (TAF) a derivative of TDF has lesser renal and bone toxicity compared to TDF. TAF may be used as a substitute for TDF for adults and adolescents. However, TAF should NOT be used in HIV/TB co-treatment and among HIV infected pregnant women. Further guidance of its use will be provided by the programme when it becomes more readily available on the market.

Second Line ARV Regimens for adults, adolescents including pregnant and breastfeeding women

Failing First Line regimen -2 NRTIs + DTG, 2 NRTIs^a + EFV (or NVP)

Preferred Regimen- 2 NRTIs^a + ATV/r, 2 NRTIs^a + DTG 

Alternative regimen- 2 NRTIs^a + LPV/r, 2 NRTIs^a + ATV/r or LPV/r 

^a If TDF + 3TC or ABC + 3TC (or FTC) was used in the failing first-line regimen, AZT + 3TC should be used in second-line ART and vice versa

Main Considerations:

• Patients failing first line (ref to ART Guidelines) should be switched to an effective second line regimen.
• Precautions in the use of DTG also apply for second and third line ARV regimens

Third Line ARV Regimens for adults and Adolescents

In adolescents older than 12 years and adults; the preferred 3^rd line ART can include Dolutegravir (50mg), Darunavir (600mg)/Ritonavir (100mg) and 2NRTIs.

Main Considerations:

• GENOTYPING TESTING IS MANDATORY PRIOR TO SWITCHING PATIENTS FAILING SECOND LINE ART with the clinician needing to actively rule out poor adherence before genotypic testing. 
• In PI experienced patients; Darunavir (600mg)/Ritonavir (100mg) should be given twice daily
• 3rd line patients with a history of INSTI use receiving DTG, should be given twice daily

First Line, Second Line and Third Line ARV Regimens for Neonates

Preferred- AZT+3TC+RAL¹

Alternatives- AZT+3TC+NVP

Special circumstances⁴ AZT+3TC+LPV/r

¹. RAL in neonates can be given for the first 6 weeks of life and then switched to regimen for children. This allows for matching of prescriptions with the EPI schedule

^4. Optimized NRTI backbone should be used: AZT following TDF or ABC failure, and vice versa.

First- Line, Second- Line and Third-Line ARV Regimens for Children

1^st line- 2 NRTI + LPV/r, 2 NRTIs + EFV, 2 NRTI + DTG

2^nd line- 2 NRTIs + DTG**, 2 NRTIs + DTG*** , 2 NRTIs + (ATV/r   or  LPV/r)

3^rd line- DRV/r  + 1-2  NRTIs Where possible consider optimization using  genotyping

**This applies to children for whom approved DTG dosing is available. RAL should remain the preferred 2nd line for those children for whom approved DTG is not available

***This applies to children for whom approved DTG dosing is available. ATV/r or LPV/r should remain the preferred 2nd line for those children for whom approved DTG is not available

Post-Exposure Prophylaxis (PEP) Adults/Adolescents:

Preferred Regimen- TDF /3TC/ DTG^a

Alternative Regimen- TDF /3TC/ ATV/r^b  

a, b: available at all health facilities from clinic upwards as starter pack and one-month course  c:* available at District/Provincial/Central Hospitals on authorization by senior person.

Main Considerations:

• Alternative treatment regimens are given if preferred regimen is not available OR  recipient is pregnant and within 12 weeks gestation OR recipient is pregnant and not on effective contraception OR if exposed client was sexually assaulted and there is potential of getting pregnant OR if exposed client had adverse drug reaction to DTG OR if source is on a DTG based regimen and could be failing
• There should be no delay in starting the best available starter pack in situations where resistance is suspected. Start the best available starter pack and then get expert advice on way forward.

Management of Latent TB Infection (LTBI) among PLHIV (addendum to the HIV

guidelines)

The TB/HIV guidance in this addendum to the Zimbabwean 2016 National ART guidelines aims to COMPLEMENT and NOT SUBSTITUTE efforts currently being implemented by the country in managing latent TB infection in PLHIV and give further guidance to HCWs on WHAT TO DO in settings where DTG based regimens are being rolled out. 

Treatment options for LTBI for children, adolescents and adults (including pregnant women) living with HIV on First line regimens 

On Efavirenz Regimen

Preferred Regimens: Rifapentine + Isoniazid   (HP) weekly for 3 months

                                             (3HP) [for both children and adults

Alternative: Isoniazid, Rifampicin + Isoniazid (HR) daily for 3 months (3HR) 

                                              [in children ONLY]

On DTG based regimen*- Preferred Regimens: Isoniazid daily for 6 months

*Those on DTG and PIs MUST use only INH for prophylaxis 

Dosing Schedule for treatment of LTBI for children, adolescents and adults (including pregnant women) living with HIV on First line regimens

Rifapentine plus isoniazid: Weekly for 3 months (12 doses) (3HP)  

                                              :Isoniazid-Individuals aged ≥ 12 years:15 mg/kg ,Individuals

                                               aged 2– 11years -25mg/kg , Maximum Dose 900mg

                                              : Rifapentine- 10.0–14.0 kg = 300 mg , 14.1–25.0 kg = 450

                                               mg ,25.1–32.0 kg  = 600 mg , 32.1–50.0 kg = 750 mg > 50

                                             kg = 900 mg, Maximum dose 900mg

Rifampicin plus isoniazid (for children ONLY): Daily for 3 months (3HR) 

                                             :Isoniazid 10 mg/kg Maximum 600mg, Rifampicin 15 mg/kg

                                             Maximum 300mg

Isoniazid alone: Daily for 6 months

                            :Adults: 5 mg/kg  Children: 10mg/kg), Maximum dose 300mg

Main Considerations:

• Patients receiving Tuberculosis Preventive Therapy (TPT) SHOULD BE REGULARLY AND ACTIVELY MONITORED FOR ADVERSE DRUG EVENTS (ADRs) including hepatoxicity [refer to 2016 national ART guidelines] at every clinic visit. Caution should be taken on use of IPT on pregnant women where potential risk for ADRs is high 
• Rifapentine and Rifampicin are contraindicated in patients on concurrent treatment with Protease inhibitors or DTG and SHOULD BE AVOIDED.

? REPEAT DOSING FOR 3HR or 3HP is NOT RECOMMENDED 

? PATIENTS ON INH OR 3HP or 3HR COURSE WILL REQUIRE CO-TREATMENT WITH PYRIDOXINE to prevent peripheral neuropathy [refer to 2016 national ART guidelines for dosing]

11.1 Prevention of Occupational Exposure in Health Facilities

All health facilities in the private and public sector should adopt a policy for the prevention of occupational accidental exposure to blood-borne pathogens. Universal precautions (i.e., the use of disposable latex gloves when handling bodily fluids, single-use equipment, and proper management of sharp and contaminated materials) should be observed by all levels of healthcare workers. Universal precautions are designed to prevent transmission of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) and other bloodborne pathogens when providing health care. Under universal precautions, the blood and certain body fluids of all patients are considered potentially infectious for HIV, HBV, HCV and other blood-borne pathogens. Universal precautions involve the use of protective barriers such as gloves, gowns, aprons, masks, or protective eyewear, which can reduce the risk of exposure of the health-care worker’s skin or mucous membranes to potentially infective materials. Health facilities should implement universal precautions for the prevention of exposure to potentially infectious material. The programme should include the training of all employees in the handling and disposal of infectious material. All personnel should be made aware of the risks involved in improper handling of such material, and the steps necessary for preventing exposure should be clearly displayed in posters. The greatest risk of accidental exposure is in the handling of sharp objects that have been used on patients. All personnel should be taught how to safely handle and dispose of sharp objects. Messages should promote the avoidance of recapping needles, using “sharps bins” for disposing of sharps, and taking care in performing procedures. Health personnel should also be conscious that blood and secretions from patients may be infectious and that simple contamination of unbroken skin does not comprise a significant risk, but contamination of intact mucous surfaces of the mouth and eyes does. The health facility should ensure the continuous supply of personal protective equipment, educational materials, disposable syringes and needles, and sharps bins. Health facilities should ensure the availability and accessibility of medicines for post-exposure prophylaxis.

11.2 Procedure to be Followed in the Event of Injury with a Sharp Object

In the event of an injury with a sharp object, such as a needle or scalpel, that has been used on a patient or in the event of a mucous surface being contaminated with blood or secretions from a patient, the following steps should be followed:

1. Wash the exposed area thoroughly with soap and water (do not pinch or press would to try to express blood).

2. Rinse the eye or mouth with plenty of water if contaminated.

3. Report the injury to a senior member of staff or the supervisor.

4. Start the ARVs recommended for post-exposure prophylaxis immediately—these should be started within 1 hour if possible and at the latest within 72 hours of the exposure.

5. Ascertain the HIV status of the source patient and the injured health worker after providing appropriate counselling—the standard rapid HIV antibody tests should be used and the results of tests obtained as quickly as possible. Offer viral DNA or RNA testing if source is suspected to be in the window period.

6. Depending on the results of the HIV tests, the following actions should be taken:

• If the source patient is HIV-negative, no further post-exposure prophylaxis is necessary for the exposed health worker. There will be need to consider exposure to other infections such as hepatitis B.

• If the exposed health worker is HIV-positive, no further postexposure prophylaxis is necessary for the health worker. The health worker should be referred for further counselling and the long-term management of his or her HIV infection, which would have occurred prior to the exposure.

• If the health worker is HIV-negative and the source patient is HIV positive, continue ARVs for a period of one month; repeat the health worker’s HIV tests at three months and at six months after the initial test. If the health worker should seroconvert during this time, provide appropriate care and counselling and refer for expert opinion and long-term treatment.

• If the health worker refuses to be tested, he or she may have no claim for possible future compensation.

7. If it is not possible to determine the HIV status of the source patient, then assume that the source is positive and proceed according to the guidelines in the previous bullets.

8. In the event of HIV infection exposure to the HCW, the greatest risk of transmission to other individuals is in the first six weeks. The exposed Health Care Worker should be instructed to use measures to reduce the potential risk of HIV transmission to others, e.g. condom use, abstinence and refraining from blood transfusion until the 6 month serologic test is negative.

9. Healthcare workers who are breastfeeding should consider discontinuing breastfeeding following exposure to HIV. This avoids infant exposure to ARVs and HIV in breast milk should the mother be infected.

10. Post-exposure prophylaxis with hepatitis B immune globulin (HBIG) and/ or hepatitis B vaccination series should be considered for occupational exposure (within 24 hours) after evaluating the hepatitis B status of the source patient and the vaccination status of the exposed person. Hepatitis B vaccine and HBIG can be given at the same time but using different injection sites. Routine pre-exposure hepatitis B vaccination should be offered to all health-care workers. Ideally the Hepatitis C status of the source patient should be ascertained.

11.3 Post Exposure Prophylaxis after Sexual Assault (Rape or Sexual Abuse) or High Risk Sexual Encounter.

It is recommended that a victim of rape or sexual abuse or who has had an unprotected high risk sexual encounter, presenting within 72 hours of exposure be counselled and provided with the medicines recommended for post–occupational exposure prophylaxis. It is important to try to determine the HIV status of the perpetrator. If that is not possible, it may be assumed that the perpetrator is HIV-positive, and the victim is provided with the treatment as listed in the preceding section. Refer the client to the nearest support centre for sexual assault survivors.

11.4 ARVs to be used in Post Exposure Prophylaxis

Immediately after exposure, all exposed adult adolescent individuals should take the following:

•  Tenofovir 300 mg orally once daily plus

•  Lamivudine 300 mg orally once daily Plus

• Atazanavir (300mg)/ ritonavir 100mg orally once daily

The above regimen is given for one month.

The Dosage for Children is as follows: AZT + 3TC is recommended as the preferred backbone regimen for HIV post-exposure prophylaxis for children 10 years and younger. ABC + 3TC or TDF + 3TC (or FTC) can be considered as alternative regimens. LPV/r is recommended as the preferred third drug for HIV post-exposure prophylaxis for children younger than 10 years. An age-appropriate alternative regimen can be identified among ATV/r, RAL, DRV, EFV and NVP. The exposed individuals should be counselled regarding side effects prior to receiving the medicines. If the source is HIV-negative, medicine administration should be discontinued.

11.5 Toxicity Monitoring

All people on Atazanavir/Ritonavir based PEP should have a baseline liver function test and a repeat at two weeks. If there is any derangement in transaminases urgent advice must be sought. Please note that atazanavir causes hyperbilirubinaemia which is a normal part of treatment. Patients on atazanavir may develop a rash. If this happens urgent advice must be sought. If there is intolerance to Atazanavir due to rash or liver toxicity then Atazanavir/Ritonavir can be replaced with Lopinavir/ritonavir or Raltegravir or Dolutegravir. All people on Zidovudine based PEP should have a baseline full blood count. It should be repeated at two weeks looking for anaemia, neutropenia, or thrombocytopaenia. All people on Tenofovir based PEP should have a baseline U&E. It should be repeated at two weeks, looking for elevations in creatinine from baseline. If there is elevation in creatinine from baseline, then Tenofovir/Lamivudine should be replaced with Zidovudine/Lamivudine.

HBV Testing There is concern about the potential risk of hepatic flares among people with chronic HBV once TDF-, 3TC- or FTC-based PEP is stopped. Assessment of HBV infection status should not be a precondition for offering TDF-, 3TC- or FTC-based PEP, but people with established chronic HBV infection should be monitored for hepatic flare after PEP discontinuation. Among people with unknown HBV status and where HBV testing is readily available, people started on TDF-, 3TC- or FTC based PEP should be tested for HBV to detect active HBV infection and the need for on-going HBV therapy after discontinuing PEP. Sexually transmitted infections after Sexual Assault (rape, intimate partner violence, or sexual abuse) or after high risk sexual encounter Exposure to sexually transmitted infections will often co-exist with HIV exposure through sexual routes. Screening, diagnosis and presumptive treatment of sexually transmitted infections should follow established guidelines.

11.6 Access to PEP

All health facilities should have known easy access points for PEP such as the casualty or emergency room of hospitals, OI clinics, or city health or rural health clinics. In addition operating theatres and labour wards should have easy access points for PEP. A hospital ward also may be designated as an access point for PEP. Health staff or those potentially exposed to HIV through sexual assault (rape, intimate partner violence, or sexual abuse) or through a high risk unprotected sexual encounter should be able to access PEP easily 24 hours a day 365 days a year. The key to success in PEP is avoiding delay in starting PEP- ideally PEP should be started straight away within 1 hour of exposure. Health-care workers should not wait to ascertain the HIV status of the source patient, but they should start PEP straight away. Every staff member of a health care institution (whether they be a doctor, dentist, nurse, nurse aid, laboratory technician, researcher, healthcare student, domestic cleaner, security guard et al) should be trained to know what to do in the event of an occupational injury. Please note students be they medical or nursing, and also staff members under contract to hospitals such as cleaners and security guards are all entitled by right to access PEP- there should be no discrimination.

Each health care facility should have a specific PEP policy and procedure in line with National Guidelines. For occupational injuries a 24 hour started pack should be issued (or a 72 hour starter pack for a weekend) until the health care worker can be seen at a staff health clinic or its equivalent and also the HIV status of the source patient and health care worker is ascertained. The health care worker should be able to access a starter pack straight away within 1 hour of injury without delay. If the source patient is found to be HIV positive (and the health worker negative) then the healthcare worker should continue the PEP for a full 28 day course accessed through the OI clinic or Pharmacy. Thus starter packs must be kept at known 24 hour accessible sites as documented above. For those who have been sexually assaulted (rape, intimate partner violence or sexual abuse) a full 28 day course of PEP should be given at the onset (a starter pack may be started again to avoid delay of obtaining the 28 Day PEP course).

11.7 Psychosocial Support

Exposure to HIV through occupational injury or through sexual exposure is a potentially stressful event and the person will need counselling support at baseline and regularly over the 4 weeks of PEP and at the 3 month and 6 month HIV tests. Enhanced adherence counselling is recommended for individuals initiating HIV post-exposure prophylaxis as there is a high defaulter rate owing to side-effects of medication and other factors. There should be a designated Staff Heath Nurse-Counsellor or equivalent who is focus person to trace and follow-up occupational injured staff or students in an intentional way to make sure they do not default follow-up visits and to check how they are doing.

HIV Testing Services

 • As a new recommendation; the MOHCC recommends re-testing of all people newly and previously diagnosed with HIV before they initiate ART. Re-testing refers to using the same testing algorithm on a second specimen from the same individual. It should ideally be conducted by a different service provider.

• HIV self-testing (HIVST) is being recommended as an additional approach to HIV testing services.

• It refers to a process in which a person collects his or her own specimen (oral fluid or blood) and then performs a test and interprets the result, often in private or with someone that he/she trusts.

• HIVST does not provide a definitive HIV-positive diagnosis and hence people who test positive during self-testing need to confirm the positive test at a health facility and be linked to treatment and care services.

 Early Infant Diagnosis

 • Birth PCR will be done within 48hrs of birth where available for high Mother To Child Transmission risk infants ONLY.

• Early ART initiation as soon as birth PCR results are available.

• For babies who test HIV positive at birth ALWAYS retest and confirm results with repeat PCR but retesting should not delay ART initiation.

• Babies who test negative at birth (birth PCR) or not tested MUST be tested at 6 weeks.

• Infants at high risk of transmission will receive dual ARVs (AZT and NVP) for 12 weeks as prophylaxis if breastfeeding and 6 weeks if not breastfeeding.

• Cotrimoxazole must be started from 6 weeks of age even in babies on longer duration of prophylaxis and continued through adolescence. 

HIV Treatment Services

• The country has adopted the “Treat ALL” recommendation where, all individuals with confirmed HIV diagnosis are eligible for anti-retroviral therapy (ART) irrespective of WHO clinical stage or CD4 count.

• Low-dose 400 mg Efavirenz-based regimens will be phased in and will initially be prioritized to adolescents living with HIV and other HIV infected individuals who cannot tolerate 600 mg Efavirenz or Nevirapine containing ARV regimens. Treatment Monitoring

• Viral load should be monitored routinely at 6 months and at 12 months after ART initiation, and then annually thereafter.

• A CD4 test is recommended at baseline to determine degree of immune suppression of a patient to inform ‘differentiated care’ for the patient. However, CD4 count is no longer used to assess eligibility for ART initiation.

 • The frequency of clinic visits has been reduced. When clients are clinically stable and on chronic medication, they do not necessarily need to be seen by the clinician at every visit.

 • A stable patient on ART should be seen for a clinical assessment every 6 months.

• A stable patient on ART is defined as someone who:

 -Has no current OIs, has a VL<1,000 copies/ml and is at least 6 months on ART

 -Where viral load is not available the client should have no current OIs, a CD4>200 copies/ml and be at least 6 months on ART PMTCT

• VL should be done on all HIV positive pregnant women who are on ART at first ANC visit and repeated 6 monthly throughout the breast feeding period

• Pregnant women not yet on ART or those newly diagnosed to be HIV positive on the first ANC booking should be initiated on ART on the same day of first booking and should get a VL after 3 months of starting ART

• Viral load testing during pregnancy and breastfeeding period is needed to stratify HIV exposed infants as either high risk or low risk. A high risk infant is defined as follows;

• An infant whose mother has a high maternal viral load >1000copies/ ml during the last 4 weeks before delivery

• An infant born to HIV infected woman who has received less than 8 weeks of ART at the time of delivery

• An infant born to a newly diagnosed HIV infected woman during labour, delivery and postpartum (Incident HIV infection)

 • High-risk infants require dual prophylaxis of Daily AZT plus NVP for 12 weeks among the breast-fed infants and Daily AZT plus NVP for 6 weeks among the formula-fed infants Pre-Exposure Prophylaxis (PrEP)

• These guidelines recommend Pre-Exposure Prophylaxis (PrEP) which should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination prevention approaches.

• The MOHCC will implement PrEP using a phased approach. An implementation plan and Standard Operating procedures (SOPs) on PrEP will be developed and shared by MOHCC to guide the introduction and scale up of PrEP. Post Exposure Prophylaxis (PEP)

• The new guidelines recommend the use of TDF/3TC/ATV/r for adults and adolescents for PEP

• There is a more pronounced presence of guidelines pertaining to sexual assault (rape, intimate partner violence, sexual abuse) Reporting Adverse Drug Events

4.1 Goals of ART

The aims of ART are as follows:

 • Maximal and durable suppression of replication of HIV

 • Restoration and/or preservation of immune function

• Reduction of HIV-related morbidity and mortality

• Improvement of quality of life

• Prevention of mother-to-child transmission of HIV (vertical transmission)

• Reduction of transmission of HIV from infected to uninfected individuals through use of ARVs by the infected individual now commonly known as ‘Treatment as prevention’

Prior to starting ART, patients should be assessed for readiness to take ARVs; the ARV regimen; dosage; and scheduling; the likely potential adverse effects; and the required monitoring. Both medical and psychosocial issues need to be addressed before initiating ART. Patients should be adequately counselled about adopting appropriate lifestyle measures such as safer sex practices (including use of condoms), and any other psychosocial problems that may interfere with adherence (e.g., alcohol, psychiatric disorders) should be addressed. Efforts should be made to reduce the time between HIV diagnosis and ART initiation based on an assessment of a person’s readiness. At each clinic visit, always screen for tuberculosis using a TB symptom checklist, advice patients about adequate nutrition and the importance of medicine adherence and regular follow-up care. People taking ARVs should also be regularly asked about whether they are taking other medications including herbal remedies that may interfere with the efficacy of ARVs. The ART programme should promote treatment literacy for PLHIV including information on the benefits of early treatment, the risks of delaying treatment, the required life-long commitment for adherence to treatment. Early treatment initiation is associated with clinical and HIV prevention benefits, improving survival and reducing the incidence of HIV infection at the community level. Increasing evidence also indicates that untreated HIV may be associated with the development of severe non-AIDS defining conditions including cardio-vascular disease, kidney disease, liver disease and neurocognitive disorders.

Health workers should retest all people newly and previously diagnosed with HIV before they initiate ART. Retesting should ideally be conducted by a different service provider with a different specimen.

4.2 Medical Criteria for Initiating ART in Adults and Adolescents

All individuals with a confirmed HIV diagnosis are eligible for anti-retroviral therapy (ART) irrespective of WHO clinical stage and CD4 count level i.e. TREAT ALL.

As a priority, initiate ART in all individuals with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) or CD4 count less than or equal to 350 cells/ mm3. It is also recommended to initiate ART, as a priority, in the following categories of patients regardless of CD4 cell count:

 • Active TB disease

• Pregnant and breast-feeding women with HIV

• Individuals with HIV in sero-discordant relationships

• HBV co-infection with severe chronic liver disease Once an individual is confirmed to be HIV positive; health workers should provide adequate counselling and start ART within a week. However, for those patients who are not ready yet to start ART, they should receive on-going counselling and support.

 EXCEPTIONS: Pregnant and breast-feeding women should be started ART on the same day of HIV diagnosis. Patients with CD4 cell count <100 Patients with low CD4 below 100 should be fast-tracked for treatment initiation. They should be screened for symptomatic TB and cryptococcal disease. They should receive cotrimoxazole and isoniazid (INH) prophylaxis like all other patients and should be closely monitored for 3 months as this is their highest risk period for bacterial infections and TB or cryptococcal IRIS. Health workers should educate them and their families to report immediately to a health facility if they are unwell whilst their CD4 cell count is< 100 copies.

The revised medical criteria i.e. treating all individuals who are HIV infected, means that many more PLHIV will be eligible for ART and that will include many healthier people. Given our limited resources as a country, there will be need to prioritize as indicated above. The AIDS and TB Directorate of the MOHCC will regularly advise you on availability of funds to procure ARVs, so as to ensure that those started on ARVs are maintained on them to reduce the potential development of HIV medicine resistance.

4.3 Psychosocial Criteria for Initiating ART

 Consider the following psychosocial criteria when initiating ART:

• Has the patient been adequately counselled and informed about ARVs?

• Is a treatment partner available and/or has disclosure been made to that treatment partner (strongly encouraged)?

• Is there an easy method of following up on the patient?

• Is the patient ready to take medications indefinitely?

4.4 Reasons for Deferring ART A patient may be deferred (delayed) from starting therapy if the patient

• has cryptococcal meningitis (defer for at least a month)

• needs further psychosocial counselling (e.g.for alcohol problems),

• has TB (defer starting ART for at least 2 weeks)

• needs further information on HIV and AIDS,

• is terminally ill and unable to swallow oral medication (palliative care is then offered to such a patient). Such patients should be offered continued monitoring and close follow-up as well as counselling so that ART can be commenced at an appropriate time.

 4.5 Adherence to ART

 WHO defines treatment adherence as ‘the extent to which a person’s behaviour- taking medications, following a diet and/or executes lifestyle changes corresponds with agreed recommendations from a health care provider. It should be noted that motivation to start and adhere to treatment may be more difficult for people who feel well and have higher CD4 counts than for people who are ill. Therefore, health workers should put special emphasis on adherence counselling for this particular group of patients. Efforts to support adherence should start before ART initiation and should include basic information about HIV, the ARV medicines, expected adverse events, preparations for long-term ART. Many factors affect adherence to treatment. Patients may just forget to take their ARVs, be away from home, be depressed or may abuse alcohol. Medication factors may include adverse events, pill burden, dietary restrictions. Health care factors include medicine stock outs, long distances to health facilities and costs related to care. Effective adherence support interventions include client-centred behavioural counselling and support, support from peer educators trained as “expert patients,” community treatment supporters and mobile text messaging. High quality evidence from randomized trials has shown that text messages contributed to reduced non-adherence and unsuppressed viral load. Other interventions involve encouraging people to disclose their HIV status and providing them with adherence tools such as pill boxes, diaries, and patient reminder aids. During follow-up, patients should be assessed for adherence to whatever treatment plan has been agreed upon (OSDM, 2016).

 4.6 ART in Adolescents

4.6.1 Who is an Adolescent?

The WHO defines an adolescent as a child between the ages of 10 and 19 years. This period of life encompasses many physiological and psychological changes that should be taken into account when treating an adolescent. Adolescence is characterized by rapid physical, neurodevelopmental, emotional and social changes. This age- group appears to be underserved by current HIV services. They have significantly worse access to ART services than adults, high risk of loss to follow-up, sub-optimal adherence, and require comprehensive health care and support services. Perinatally infected adolescents are likely to experience chronic diseases and neuro-developmental growth and pubertal delays. However, adolescents who acquire HIV behaviourally may not face the same clinical problems, but may potentially have challenges relating to stigma and lack of support to access care.

 4.6.2 HIV Testing Services (HTS) for Adolescents

• It is important to increase uptake for HIV testing services by adolescents through: provider-initiated HTS coupled with other entry services such family planning services, VMMC and immunization campaigns

• Ensuring that all health facilities are oriented towards the adolescent- friendly health services approach Special attention should be given to: Post-test counselling; appropriate and successful linkage to prevention, treatment and care services; and consent and confidentiality, which are major concerns for adolescents Adolescents should be counselled about potential benefits and risks of disclosure of their HIV status and empowered and supported to determine if, when, how and to whom to disclose to.

 4.6.3 Principles of ART in Adolescents

The principles of therapy are similar to those in adults and children. However, one should bear in mind specific issues when monitoring and treating HIV positive adolescents, which are discussed in the following sections.

Dosage of ART Decisions regarding dosage for adolescents should take the following factors into account:

• The age at which to start adult dosing can be difficult to determine.

• Stunting and wasting which are common among HIV-positive adolescents.

• It is recommended that those under the weight of 25 kg should be dosed according to paediatric dosing guidelines. Thus, all adolescents— regardless of age—should be weighed before commencing ART and at each visit.

4.6.4 Staging HIV-Positive Adolescents

 HIV-positive adolescents are at risk not only of the HIV-associated infections typically used to stage HIV-positive adults but also of chronic non-infective complications typically used to stage paediatric HIV. These specifically include chronic lung disease, lymphoid interstitial pneumonitis (stage 3) and HIV-associated cardiomyopathy/nephropathy and stunting (stage 4). Such conditions should be taken into account when staging HIV-positive adolescents

4.6.5 Monitoring of HIV Disease

 In monitoring adolescents, remember the following:

• Stunting and pubertal delay are common.

• As well as CD4 count and Viral load monitoring, clinical monitoring should include measurement of height and weight at every clinic visit as well as evaluation of pubertal stage using Tanner staging every six months.

• Girls should specifically be asked about menstruation, including age of menarche and timing of menstrual cycles.

4.6.6 Chronic Complications

As well as looking for and treating OIs, clinicians should monitor patients for chronic complications such as heart failure, lung and skin infections.

4.6.7 Disclosure

 Lack of knowledge of HIV status can result in poor adherence to ART. Adolescents should be involved in the discussion about HIV testing, and their HIV status should be disclosed to them. Do not assume that adolescents are aware of their HIV status. Unless exceptional circumstances make it difficult for an adolescent to understand his or her HIV status (severe mental disability), it is strongly recommended that HIV status be disclosed before the patient starts ART. Disclosure is a gradual process and should be carried out with the involvement of the guardian, a counsellor, and the doctor.

4.6.8 Adherence

 Adherence is particularly problematic in adolescents. Particular attention should be paid to assessing adherence at every visit and to providing adherence support. Counselling on adherence should include exploring specific reasons that may contribute to poor adherence. Adolescents face many psychosocial issues that can affect their adherence, and those should be assessed:

• In particular, ways of supporting attendance at clinic appointments and taking medicines while at school (especially for those at boarding schools) should be addressed.

• Patients should be encouraged to identify a family member who will help support their treatment. • Peer support at the clinic level can be very helpful in encouraging adherence e.g. through introduction of Community Adolescents Treatment Support (CATS).

• Counselling should be adolescent-friendly, and counselling patients on their own without the presence of guardians/parents is recommended whenever possible. This ensures that patients can talk about personal issues that affect their ability to take medicines.

4.6.9 Education, Information and Services on Sexual and Reproductive Health

Education about sexual and reproductive health should be part of the counselling and treatment of HIV-positive adolescents. Education and information should be tailored according to the patient’s own knowledge and maturity. This clearly varies across the age group and should be assessed during counselling. Specific information/services that should be given to adolescents include information on;

• Avoiding onward HIV transmission, including delaying sexual relationships and using condoms;

 • Specific modes of HIV transmission (it is a common misconception that kissing and non-sexual physical contact can transmit HIV); and

• Where to access family planning services and STI treatment and how to seek help in cases of sexual assault.

• Where available HPV vaccine should be administered to young girls

4.6.10 Transitioning from Adolescence into Adulthood

Transitioning from adolescence to adulthood can be a difficult period even for those without HIV. Changes in their bodies may affect their emotions and behaviours. HIV is an added burden and adolescents who have previously adhered to therapy from childhood may start to default treatment. Health Care workers should anticipate this and discuss it with adolescents and caregivers as part of the treatment plan. Health workers should prepare adolescents to take control of their own treatment and be less dependent on caregivers. Service providers should encourage mature adolescents (in consultation with caregivers) to attend clinic visits alone where appropriate. As a last step to transitioning to adult care, adolescents should be familiarized with the adult care setting and procedures.

6.1 Introduction

Mother to child transmission of HIV is an important contributor of HIV transmission. The MOHCC is committed to the elimination of MTCT of both HIV and Syphilis and as such efforts should be intensified to reach this goal. The aim of ‘elimination’ is to have an eMTCT rate of HIV of less than 5% in breast-feeding communities.

The national PMTCT programme therefore aims to achieve the following targets:

• ANC coverage of ≥ 95%

• Coverage of HIV and Syphilis testing of pregnant women ≥ 95%

• ART coverage of HIV positive pregnant women of >90%

• Treatment of Syphilis sero-positive pregnant women of ≥95% The Zimbabwe PMTCT programme has four main strategies:

• Primary prevention of HIV infection among women of reproductive age

• Prevention of unintended pregnancies in HIV infected women.

• Prevention of HIV transmission from HIV infected women to their infants during pregnancy, labour, child birth and beast-feeding through HIV counselling and testing, ARV prophylaxis, ART for life for all pregnant and breast-feeding women and safer infant feeding practices

• Provision of comprehensive care to mothers living with HIV, their children and families. In view of the increasing evidence around the benefits of life-long ART for all adults and the successful uptake of Option B+ by many programmes; WHO 2015 ARV guidelines now recommend moving away from ‘options’ for PMTCT to providing lifelong ART for all HIV positive pregnant and breastfeeding women regardless of their immune status or clinical stage of the woman.

6.2 HIV Testing Services for Pregnant and Lactating Women

 PITC for women should be considered a routine component of the package of care in all antenatal, childbirth, postpartum and paediatric care settings. In our settings, where breastfeeding is the norm, lactating mothers who are HIV negative should be retested periodically throughout the period of breastfeeding.

 Health workers should retest previously HIV-negative women as follows:

• first trimester of pregnancy

• third trimester/ or at delivery

• 6 weeks post-natal and

• 6 monthly during the breastfeeding period.  In antenatal care settings, couples and partners should be offered voluntary HIV testing services with support for mutual disclosure.

Service package for pregnant women whose test result is HIV positive (including those already on ART) should include the following:

• HIV prevention during pregnancy and breastfeeding period, including dual protection, condoms and PrEP

• Discussion of childbirth plans and encouragement to deliver in a health facility for health reasons and to ensure access to services for PMTCT

• Use of ARV drugs both for the mother’s health and to prevent transmission to the infant

• Importance of partner testing and information on the availability of couples testing services

• Screening for TB and testing for other infections, such as syphilis and hepatitis B

• Counselling on maternal nutrition, including iron and folic acid supplementation

  Advice on infant-feeding and support to carry out the mother’s infant feeding choice

• HIV testing for the infant and necessary follow up for HIV-exposed infants

• Counsel on sexual and reproductive health including family planning and the need for dual contraception (reliable hormonal contraceptives plus barrier methods i.e. male and female condoms)

Acquisition of HIV infection in pregnancy or during the breastfeeding period is associated with peak viremia and increased risk of HIV transmission to the baby. As such women at risk of new infections (sero-discordant couples), should be provided with PrEP during pregnancy and breast feeding

6.3 When to start Lifelong ART in HIV Positive Pregnant and Lactating Women

 All HIV positive pregnant and breastfeeding women should initiate lifelong ART as soon possible after their HIV positive status is confirmed irrespective of their CD4 count or WHO clinical stage; and continue ART throughout the breastfeeding period and beyond. Health workers should conduct rapid assessment of a person’s readiness for ART (refer to OSDM, 2016). In the context of pregnancy and breastfeeding and to minimize risk of MTCT, same day initiation is recommended.  Women who are not yet ready for lifelong ART should be initiated on triple ARVs (ART), which should be continued at least for the duration of breastfeeding. In Zimbabwe, due to the high HIV prevalence in ANC and the need to scale up towards eliminating mother to child transmission of HIV, ART should be initiated urgently in all pregnant and breastfeeding women, even if they are identified late in pregnancy or postpartum, because the most effective way to prevent mother-to-child HIV transmission is to reduce maternal viral load.

ART should be initiated and maintained in eligible pregnant and postpartum women and in infants at maternal and child health-care settings, with linkage and referral to on-going HIV care and ART at the end of 5 years or earlier at 2 years as appropriate.

First and second-line ARVs for Pregnant and breast-feeding women Pregnant and Lactating women

First line therapy 2nd line therapy

Preferred  Options -TDF + 3TC+ EFV600

If TDF was used as first line, use AZT plus 3TC plus ATV/r 

If LPV/r If AZT was used as first line, use TDF plus 3TC plus ATV/r or  LPV/r

Alternative Options AZT + 3TC + EFV600 AZT + 3TC + NVP TDF + 3TC + NVP

There is INSUFFICIENT DATA for using low dose EFV in pregnant women, and therefore TDF +3TC+ EFV600 will continue to be used for HIV positive pregnant women till more information on dosing becomes available.

 6.4 Use of Viral Load Testing in Pregnancy

 Viral load testing has additional value for assessing the risk of transmission of HIV from mother to child. For HIV infected pregnant and lactating women on ART, Health workers should

• Perform a Viral load at first ANC visit and provide adherence counselling

• If VL is > 1000 copies/ml explore possible reasons for their high viral load, commence enhanced adherence counselling immediately and VL should be repeated after 1 months and patient managed according to the national VL algorithm

• For women with a VL< 1000 copies/ml repeat VL every 6 months throughout pregnancy and breast feeding

For newly identified HIV pregnant women and those who initiate ART on their current pregnancy health workers should

• Perform a VL Test after 3 months from date of commencing ART recommendations of what to do for VL > 1000 copies/ml and < 1000 copies/ml are the same as above

6.5 HIV Exposed Infant Prophylaxis

VL testing during pregnancy and breastfeeding period is needed to stratify HIV exposed infants as either high risk or low risk. It is important not to use a “one size fits all” for infant prophylaxis as infants are not all at the same risk for HIV transmission.

A high risk infant is defined as follows:

• An infant whose mother has a high viral load >1000copies/ml during the last 4 weeks before delivery

• An infant born to HIV infected woman who has received less than 4 weeks of ART at the time of delivery

• An infant born to a newly diagnosed HIV infected woman during labour, delivery and postpartum (Incident HIV infection) All infants who do not meet the criteria for ‘high-risk’ infants are classified as ‘low-risk’ infants.

 Prophylaxis for the high and low risk infants

Infant age Dosing

NVP Dosing AZT

Birth to 6 weeks Birth weight 2000−2499 g -NVP 10 mg once daily (1 ml of syrup once daily) AZT 10 mg twice daily (1 ml of syrup twice daily)

Birth weight ≥2500 g -NVP 15 mg once daily (1.5 ml of syrup once daily) AZT 15 mg twice daily (1.5 ml of syrup twice daily)

>6 weeks to 12 weeks- 20 mg once daily (2 ml of syrup once daily or half a 50 mg tablet once daily)

No dose established for prophylaxis; use treatment dose 60 mg twice daily 6 ml of syrup twice daily or a 60 mg tablet twice daily)

Infant dosing table for Nevirapine and Zidovudine

For infants weighing <2000 g and older than 35 weeks of gestational age, the suggested doses are:

NVP 2 mg/kg per dose once daily and AZT 4 mg/kg per dose twice daily. Premature infants younger than 35 weeks of gestational age should be dosed using expert guidance.

6.7 Infant Feeding in the Context of HIV

 The Ministry of Health and Child Care (MOHCC) promotes, supports and protects breastfeeding because it is the first and best investment for a child’s nutrition and health. Appropriate feeding methods including their advantages and disadvantages should be explained to all mothers to allow them to make an informed decision.

Mothers who chose to breastfeed are advised to

• Exclusively breastfeed their infants for the first 6 months of life, introducing appropriate complementary foods at 6 months, and continue breastfeeding up to 24 months and beyond.

• Avoid mixed feeding (feeding infants with breast milk and other fluids, and semi-solid or solid foods).

• Exclusive breastfeeding is recommended however mixed feeding is not a reason to stop breastfeeding in the presence of ARV drugs.

• HIV-infected mothers may consider expressing and heat-treating breast milk as an interim feeding strategy:

• In special circumstances such as when the infant is born with low birth weight or is otherwise ill in the neonatal period and unable to breastfeed; or

• When the mother is unwell and temporarily unable to breastfeed or has a temporary breast health problem such as mastitis;

• If ARV drugs are temporarily unavailable

• Expressing breastmilk should also be taught to mothers to assist mothers to stop breastfeeding;

 • Breastfeeding mothers who decide to stop breastfeeding at any time should stop gradually within one month. Abrupt cessation of breastfeeding is not advised

 • Breastfeeding mothers should be counselled on how to solve common difficulties, such as sore nipples, perceptions of “insufficient milk,” engorgement, manual expression, and storage of breast milk

 • Breastfeeding mothers are advised to immediately seek treatment for mastitis, cracked nipples, infant mouth lesions, and thrush to decrease the risk of MTCT

 • Breastfeeding mothers should be counselled on appropriate complementary foods that must be introduce to the infants’ diet beginning at 6 months as per the Zimbabwe Infant and Young Child Feeding Guidelines. For HIV infected mothers who choose not to breastfeed, they can adopt exclusive Formula Feeding* for the first six months, introducing appropriate complementary foods at 6 months, and continue formula feeding up to 12 months and beyond if they chose. It is important to support the mother in the feeding option they may choose. The following conditions must be met in their entirety for safe Exclusive Replacement Feeding, (AFASS).

• Safe water and sanitation are assured at the household level and in the community, and

• The mother, or other caregiver can reliably provide sufficient infant formula* milk to support normal growth and development of the infant, and

• The mother or caregiver can prepare it cleanly and frequently enough so that it is safe and carries a low risk of diarrhoea and malnutrition, and

• The mother or caregiver can, in the first six months, exclusively give infant formula milk, and

• The family is supportive of this practice, and

• The mother or caregiver can access health care that offers comprehensive child health services. 6.8 Early Infant Diagnosis of HIV Infection (EID) All infants with unknown or uncertain HIV exposure being seen in health-care facilities at or around birth or at the first postnatal visit (usually 4–6 weeks) or other child health visit should have their HIV exposure status ascertained.

 This can be done in by:

• Asking if the mother knows she is HIV positive or is on ART

• Checking the hand held child health card for information on maternal HIV status

• Performing a rapid HIV test on the mother

• Performing a rapid HIV test on the baby- N.B. this can be used to assess HIV exposure only in infants less than 4 months of age. HIV-exposure status in infants and children 4–18 months of age should be ascertained by undertaking HIV serological testing in the mother 6.9 Testing of HIV Exposed Infants All babies of HIV-infected mothers are born with maternal anti-HIV antibodies that are passed on to them trans placentally. These antibodies start to wane from about 4months, and by 18 months have cleared off completely. Due to the presence of these maternal antibodies, HIV antibody tests in infants under the age of 18 months cannot be used to definitively diagnose HIV infection. Diagnosis of HIV infection in children less than 18 months requires testing for the virus itself (called virologic testing, or PCR testing). Infants with an initial positive virological test result should be commenced on ART without any delay and, at the same time, a second specimen should be collected to confirm the initial positive virological test result. Immediate initiation of ART saves lives and should not be delayed while waiting for the results of the confirmatory test.

Infants testing HIV PCR negative and those HIV-exposed infants who are well should undergo HIV serological testing at around 9 months of age (or at the time of the last immunization visit). Infants who test positive by HIV rapid test at 9 months should have a virological test to definitively diagnose HIV infection and the need for ART. Nucleic Acid Testing (NAT) at birth (birth PCR) for high Risk Infants is recommended to improve the identification of infants at highest risk for early disease progression. Nucleic acid testing (NAT) technologies that are developed and validated for use at or near to the point of care (POC) can be used for early infant HIV testing. If the birth PCR is negative, the baby should have DBS collected at 6 weeks for re-testing with PCR. It is strongly recommended that test results from virological testing in infants be returned to the clinic and child/mother /caregiver as soon as possible, but at the very latest within four weeks of specimen collection. Positive test results should be fast-tracked to the mother–baby pair as soon as possible to enable prompt initiation of ART Rapid diagnostic tests for HIV serology can be used to diagnose HIV infection in children older than 18 months following the national HIV testing strategy