recent advances in HIV - AIDS . Research in AIDS is ever continuing till its cure. here is a summary of latest advances till 2021

1. HIV- Recent Advances
Presented by :R.Rajesh
Moderator :Dr.Nidhi Bharadwaj

2. CONTENTS
• Statistics and Action Plan
• Milestones
• Diagnosis
• Prevention
• Treatment
• End Slide

3. World Statistics
• 37.7 million people living with HIV at the end of 2020 – 2/3 in Africa.
• In 2020 alone 6,80,000 died from HIV- related causes
• 1.5 million acquired HIV in 2020
• What happened to 90-90-90 goal of UNAIDS by 2020 ?
• 84% knew their HIV status
• 73% were accessing ART
• 66% were virally supressed

4. World’s Plan
• So whats next?
• By 2025 ?
• By 2030 ?
means that AIDS is no longer a public health threat

5. India in 2019
• 23,49,000 people living with HIV
• 69,000 newly infected with HIV
• 58,000 AIDS related deaths
• Maharashtra highest number. Mizoram highest prevalence.
• 837 of 1000 new infections in India are through heterosexual route
• 48% and 39% of new infections in Punjab and Tripura respectively are
through infected needles
• 76% were aware of their HIV status, 63% were on ART and 53% were
virally suppressed

6. INDIA’s Plan
• Vision of the NACO is that of ‘Paving the way for an AIDS free India
• NACP phase – 4 Extension (2017 – 2024)
• By 2024 - 80% reduction in new HIV infections
- 95 – 95 – 95
• HIV/AIDS Act 2017 – Role of Govts, Rights of HIV Person, Punishment
• 1097 national AIDS helpline

7. 7
1981
2011
1986
MILESTONES after 2011
1st AIDS case in
Chennai
1st AIDS case in
LOS ANGELES
FDA approved single
FDC tablet
COMPLERA

8. 8
2012
2014
2013
2015
Virus in Mississipi baby
• Cuba first to eliminate
mother to baby transmission
• Mississipi baby
START study – Early
therapy prevents
AIDS development
• First at- Home HIV test
• Use of Truvada for PreP
for at risk population

9. 9
2016
2018
2017
2019
Study saying HIV positive
persons having twice
cardiovascular risk
U = U Campaign
• LONDON Pt
• WHO – Drug resistant HIV
• DOULTEGRAVIR
First organ transplant between
two HIV positive person

10. 10
2020
2021 Esperanza
Loren Wellenberg
Once a month i.m
injection- Cabenuva

11. Diagnosis
Eclipse period
Seroconversion period/ window period
Acute infection
Recent infection
Chronic infection

12. Algorithms
CDC 2018 Guidelines NATIONAL HIV COUNSELLING AND TESTING SERVICES
(HCTS) GUIDELINES 2015
For blood banks & community centres

13. Algorithims
• Assays Al, A2, A3 represent three
different assays based on
different principles or different
antigenic compositions.
• Assay Al should be of high
sensitivity and A2 and A3 should
be of high specificity
• If Indeterminate : Testing should
be repeated on a second sample
taken after 14–28 days
• Partner testing
• HIV-TB Cross referral

14. TESTING
EVOLUTION

15. NUCLEIC ACID TESTS
• PCR based assays
• Isothermal Amplification based assays
• Loop mediated isothermal amplification based assays
• Recombinase polymerase amplification based assays
• NEWER TECHNOLOGIES
1. Paper and flexible material based assays
2. Plasmonic nanoparticles and photonic crystal based platforms
These are used for early diagnosis as fast as 10 to 12 days and
also for monitoring

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Prevention

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BEHAVIORAL INTERVENTIONS STRUCTURAL INTERVENTIONS

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BIOMEDICAL
INTERVENTION
S
• Male and female condoms
• Sex and reproductive health services
• Voluntary medical male circumcision 2020(dec by
60% in heterosexually got HIV)
• Antiretroviral drugs for the prevention of mother-to-
child transmission, pre-exposure prophylaxis, post-
exposure prophylaxis and treatment as prevention
• HIV testing and counselling
• Testing and treatment of sexually transmitted
infections
• Needle and Syringe programmes
• Opioid substitution therapy
• Blood screening.

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Pre exposure Prophylaxis
• Daily oral PrEP containing tenofovir for people at risk*(2016)
• Event-driven PrEP, for cisgender MSM – (2+1+1)(2019)
• Dapivirine vaginal ring(2021)
Injectable Cabotegravir under trial

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POST EXPOSURE PROPHYLAXIS
• TDF + 3TC (or FTC) + DTG as single tab for 28 days (2019)
• With in 72 hrs
• HIV test at 3 months after exposure

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HIV Life Cycle

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DRUGS
• NRTIs : Abacavir(ABC), Emtricitabine(FTC), Lamivudine(3TC),
Tenofovir(TDF), Zidovudine(AZT) – 1st approved drug
• NNRTIs : Doravarine(DOR) 2018, Efavirenz(EFV),
Etravirine(ETR), Nevirapine(NVP), Rilpivirine(RPV) 2011
• Pis : Atazanavir(ATV), Darunavir(DRV), Fosamprenavir(FPV),
Saquinavir(SQV), Tipranavir(TPV), Ritonavir(RTV)* as
enhancer
• INSTIs : Doultegravir(DTG)2013, Raltegravir(RAL)2017,
Cabotegravir(CAB)2021

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DRUGS
• Fusion Inhibitor: Enfuviritide(T-20)
• CCR-5 Antagonist: Maraviroc(MVC)
• Attachment Inhibitors : Fostemsavir(FTR)2020,
• Post-Attachment Inhibitor : Ibalizumab-uiyk (IBA)2018
• Pharmacokinetic Enhancers : Cobicistat(COBI)2014
• JULUCA – 2 drug FDC containing dolutegravir and rilpivirine approved
as treatment 2017 for HIV-1 suppressed patients
• Dovato (dolutegravir and lamivudine) for all patients 2019
• CABENUVA (cabotegravir; rilpivirine) once a month i.m inj.2020

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ART
ASSESSMENT
Medical history
Physical examination
Basic Lab investigations plus CD4
WHO clinical staging
Look for OI

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Medical history checklist
• Hiv testing
• Hiv risks
• Review of symptoms
• Past history of hiv related illness
• TB – 4symptoms screen, STIs
• ART history
• Medication history
• Allergy
• Vaccination status
• Gynecological history
• Pregnancy and contraception history

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Physical examination
• Vitals
• Appearance
• Mouth
• Skin
• Lymph nodes
• Chest
• Abdomen
• Ano-genital
• Neurological

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WHEN TO START
SCENARIO RECOMMENDATION
Adult diagnosed with HIV On same day after confirmation & assessment
With suspected TB Initiate ART – Investigate – start ATT with in 7
days if confirmed
Being treated for HIV- associated TB including
MDR
With in 2 weeks of ATT start ART
Being treated for HIV- assosiated TB meningitis ART should be delayed at least 4 weeks and
initiated within 8 weeks
Living with HIV and now diagnosed with TB not
receiving ART or ATT
ATT should be started first f/b ART within 2 weeks
of ATT
Living with HIV with cryptococcal meningitis After 4-6 weeks of antifungal treatment ART to be
started

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Scenario NACO oct 2018 guidelines
Unidentified acute fever Diagnose and treat first then
ART
Malaria, Pneumonia, Acute
Diarrhoea
Start ART when treatment is
completed
PCP Start ART when PCP treatment
is completed
Invasive fungal infections Start ART when patient is
stabilised
CMV Start CMV treatment then ART
after 2 weeks
Suspected MAC,
Cryptosporidiasis,
Microsporidiasis
Start ART (ART may resolve
these problems)
Skin conditions such as
PPE and Seborrhoeic
Dermatitis, Psoriasis,
HIV-related Exfoliative
Dermatitis
Start ART (ART may resolve
these problems)

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WHAT TO START
Why Doultegravir has become new hero ?
1. Effective in controlling viral load
2. Few interactions
3. Less side effects
4. High barrier to resistance
5. Latest studies shows neural tube defects in babies born to hiv pregnant
woman on doultegravir Significantly lower than previous studies.

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2nd line
When to shift ?

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3rd line

33. Monitoring
• General lab testing for drug side effects
• A baseline CD4 is useful for immunological failure and OI.
• Timing of CD4 & viral load should be synced
• Treating clinician can order CD4 and viral load when deemed
necessary
• HIV – 2 monitoring is currently through CD4 levels only
• CD4 counting can be stopped if it is more than 350 & can be started if
clinical or virological failure
• CD4 counting is through flow cytometry and viral load is through
RTPCR technology.

34. Monitoring
• The goal of antiretroviral therapy is to suppress the plasma HIV
RNA below the limits of assay detection (eg, <50 copies/mL)
• Virological failure: load more than 1000 in new pt after 24 weeks
of ART or recurrence of viremia to >1000 copies/mL on two
consecutive measurements taken approximately one month
apart in patient who had record of supressing after giving 3
sessions of adherence counselling
• Clinical failure : new or recurrent clinical event of WHO stage 4
after at least 6 months of ART

35. Monitoring
• Immunological failure:
1. Fall of CD4 count to pre- therapy levels after 6 months of ART
2. 50% fall from the on- treatment peak value
3. Persistant CD4 Levels < 100 after 12 months of ART
• Adherence, drug-drug and drug-food interactions, drug tolerability, HIV RNA
level and CD4 T lymphocyte (CD4) cell count trends over time, ART history,
and prior and current drug-resistance test results.

36. Monitoring
• CD – 4 Levels :
• Viral load

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Viral load monitoring
is preferred way of
monitoring.
POC viral load
testing may be used

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ART resistance
• Among people initiating first-line ART, high prevalence of
pretreatment HIV drug resistance to NNRTIs is seen reaching
10% or above in 12 of 18 countries(disc. ART > Naïve)
• The overall prevalence of transmitted drug resistance in Naïve is 11.3%
(6/53).Surveillance drug resistance mutations to NNRTI were observed in
8.3% (n = 4) of the 48 RT sequences analyzed. In Chennai 2019 study
• Types of resistance: Induced Resistance & Primary Resistance

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Mechanisms of resistance
• Resistance to NRTI’s occurs through 2 mechanisms: the first is
mutation of the residues that results in reduced incorporation of the
NRTI into the growing DNA chain
• The second mechanism of NRTI resistance is associated with
enhanced removal of drug from its site of attachment at the end of
the DNA chain
• Resistance to NNRTIs class of agents occurs mainly through
mutation of hydrophobic RT residues within the binding pocket for
the NNRTIs
• Resistance to protease inhibitors occurs primarily as a result of
amino acid mutations that arise within or proximal to the catalytic
binding site to the dru

40. 40

41. 41
ART toxicity & drug interactions
DRUG NAME ADVERSE REACTIONS INTERACTIONS
TENOFOVIR AKI,CKD,Lactic acidosis,
hepatomegaly
Ledipasvir, velpatasvir, Lithium
Doultegravir Hepato toxicity, Hyper sensitive
reactions, Insomnia
Carbamazepine, phenobarbital
,phenytoin, Rifampicin,
Metformin
Efavirenz Gynaecomasatia, CNS &
Hepato toxicity, hypersensitive
reactions
Bedaquillin, Artmisinins,
Lumifantrine,
Quetiapine,Amlodepine, statins,
harmonal contraceptives
Lamivudine Minimal. Rarely rash Emtricitabine, Orlistat, sorbitol,
Tafenoquine

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CO- INFECTIONS
• Chronic HBV co- infection: TLE is preferred regimen
1. If regimen has to be changed still T & L should be continued
along with new regimen.
2. Entecavir can also be used/ added for HBV
• Chronic HCV co-infection:
1. Sofosbuvir 400 mg + Daclatasvir 60 mg for 12 weeks for non-
cirrhotic patients
2. Sofosbuvir 400 mg + Velpatasavir 100 mg for 12 weeks for
cirrhotic patients for compensated patients
3. Sofosbuvir 400 mg + Velpatasavir 100 mg for 12 weeks for
cirrhotic patients for decompensated patients

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PROPHYLAXIS FOR OI
• For PCP & Toxoplasma –
1. Double strength co-trimoxazole daily for HIV +ve with CD4 <
350 or WHO stage 3 / 4
2. If allergic Dapsone 100 mg / day
• For Cryptococcal Meningitis –
1. For secondary prophylaxis Tab Fluconazole 200 mg daily
2. Till CD4> 200 measured 2 occasions 6 months apart

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PROPHYLAXIS FOR OI
• Tuberculosis : 3 recommendations 2020
1. six or nine months of daily isoniazid
2. three-month regimen of weekly rifapentine plus isoniazid
3. three-month regimen of daily isoniazid plus rifampicin
• MAC :
1. Primary prophylaxis is not indicated in patients who initiate ART
immediately regardless of CD4 count
2. The exception to this includes patients with a CD4 count <50 cells/microL
who are not on fully suppressive ART
3. If indicated Azithromycin 1200 mg once weekly or Clarithromycin 500
mg BD till 6 months after achieving viral suppression

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Vaccines in HIV positive persons
Vaccine CDC recommendation
Hepatitis A Yes
Hepatitis B Yes
DTP-containing vaccines Yes
HiB Maybe
HPV Yes
Influenza Yes
Measles Yes
Rubella No
Meningococcal , pneumococcal Yes
Covid 19 Yes
Caution ⚠️ with live
vaccines

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REFERENCES
• www.unaids.org
• http://naco.gov.in/
• www.avert.org
• www.cdc.gov
• Md Alamgir Kabir, Hussein Zilouchian, Massimo Caputi & Waseem Asghar(2020): Advances in HIV
diagnosis and monitoring, Critical Reviews in Biotechnology, DOI:10.1080/07388551.2020.1751058
• www.who.int
• www.fda.gov
• https://hivinfo.nih.gov/home-page
• https://clinicalinfo.hiv.gov/en
• Manohar N, Hemalatha H, Narayanaiah C, Ramesh K, Nandagopal K, Pattabiraman S,
et.al.Transmitted HIV-1 Drug Resistance in a Treatment-Naive Cohort of Recently Infected
Individuals from Chennai, India. AIDS Reasearch and Human Retroviruses2019;35(8):775-779.
• uptodate

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THANK YOU