HIV/AIDS in Obstetric and Gynecological, Practice, Including PMTCT

HIV class: Lentivirus

Retrovirus: single stranded RNA

Transcribed to double stranded DNA by reverse transcriptase

Integrates into host genome

Can lie dormant within a cell for many years, especially in resting (memory) CD4+ T4 lymphocytes

HIV type (distinguished genetically)—

• HIV-1 – worldwide pandemic (current approximately 33.4 M people)
• HIV-2 – isolated in West Africa

HIV-1 groups—

• M (major): cause of current worldwide epidemic
• O (outlier) and
• N (Cameroon): rare

HIV-1 M subgroups (clades)—

• Clades differ from each other genetically
• >10 identified (named with letters A to K)
• Descended from common HIV ancestor
• One code tends to dominate in a geographic region
• Different clades have different clinical and biologic behavior

The AIDS epidemic in Nigeria

Nigeria (tenth largest country in the world, the most populous country in Africa).

Infection primarily heterosexual transmission.

The results from 2008 HIV seroprevalence sentinel surveys involving pregnant women attending antenatal clinics by the Federal Ministry of Health showed a national prevalence of 4.6%. -Generalized.

Early history of the epidemic

1981 Cases of Pneumocystic carinii pneumonia and Kaposi's sarcoma in the USA

1983 Discovery of the virus. First cases of AIDS in the UK

1984 Development of antibody test

Sub-Saharan Africa and HIV/AIDS

Home to 10% of world's population and two thirds of the HIV/AIDS burden

Accounts for 2/3 of all new infections globally

¾ of all AIDS deaths world-wide in-spite of recent improvements in access to antiretroviral treatment

>90% of all infant infections through MTCT

HIV Estimates in Nigeria

No of PLWH- 2.95 million (Male-1.23, Female-1.72 million)

Annual HIV+ Birth-56, 681

Cumulative AIDS Death- 2.99million (Male-1.38, Female-1.61)

Annual AIDS Death-280,000 (Male-123,000, Female-157,000)

Number requiring ART- 833,000 (Adult-740,000, Children-92,000)

New infection 380, 000 (Adult-323,000, Children- 57,000)

Total AIDS orphaned-2.23million

Detectable components or products of viral infection for diagnosis—

• Antibodies-ELISA (reactive/non-reactive), Western blot (positive, negative, Indeterminate)
• Antigen- antigen P24
• Nucleic acid- polymerase chain reaction
• Whole (viable) virus- viral culture

ELISA (enzyme Linked immuno-sorbent assay) - tests for a number of antibody proteins in combination. Very sensitive but not entirely specific.

Rapid tests- provide results in about 10 minutes. Sensitivity approaches 100%; specificity is >99%. Positive results need to be confirmed with standard serology. Useful in situations where immediate results are important to management decisions e.g. occupational exposure, STD clinics and emergency rooms.

Western immuno-blot test- confirmatory test. Very specific for HIV.

Sexual transmission

Body fluids

Donated organs

Vertical transmission

• In utero
• At birth
• Durinng breastfeeding

Intravenous drug users

Immune suppression

• HIV attacks white blood cells, called CD4 cells that protect body from illness.
• Over time, the body's ability to fight common infections is lost.
• Opportunistic infections occur.

Direct infection of organ systems

• Brain (HIV dementia)
• GIT (wasting)
• Heart (cardiomyopathy)

AIDS-defining conditons without laboratory evidence of HIV

Diseases diagnosed definitively—

• Candidiasis: esophagus, trachea, bronchi or lungs
• Cryptococcosis: extrapulmonary
• Cryptosporidiosis with diarrhea persisting > 1 month
• Cytomegalovirus disease other than in liver, spleen, nodes
• Herpes simplex virus (HSV) infection
• Mucocutaneous ulceration lasting 1 month
• Pulmonary, oesophageal involvement
• Salmonella septicaemia: recurrent
• HIV wasting syndrome
• Recurrent pneumonia within 1 year
• Invasive cervical cancer
• Kaposi's sarcoma in patient < 60 years of age
• Primary cerebral lymphoma in patient < 60 years of age
• Lymphoid interstitial pneumonia in child < 13 years of age
• Mycobacterium avium: disseminated.
• Mycobacterium kansasiii: disseminated
• Pneumocystis carinii pneumonia
• Progressive multifocal leukoencephalopathy
• Cerebral toxoplasmosis

Diseases diagnosed presumptively

• Candidiasis: esophagus
• Cytomegalovirus retinitis with visual loss
• Kaposi's sarcoma
• Mycobacterial disease (acid-fast bacilli; species not identified by culture): disseminated
• Pneumocystis carinni pneumonia
• Cerebral toxoplasmosis

AIDS-defining conditions with laboratory evidence of HIV

Diseases diagnosed definitively—

• Recurrent/multiple bacterial infections in child <13 year of age
• Coccidiomycosis - disseminated
• HIV encephalopathy
• Histoplasmosis - disseminated
• Isosporiasis with diarrhea persisting> 1 month
• Kaposi's sarcoma at any age
• Primary cerebral lymphoma: diffuse, undifferentiated B cell type, or unknown phenotype
• Any disseminated mycobacterial disease other than M. tuberculosis
• Mycobacterial tuberculosis at any site

Summary of Natural History

HIV multiplies inside the CD4 cells, destroying them.

As CD4 cell count decreases and viral load increases, the immune defenses are weakened.

People infected with HIV become vulnerable to opportunistic infections.

HIV is a chronic viral infection with no known cure.

Without ARV treatment, HIV progresses to symptomatic disease and AIDS.

HIV started as disease of MSM

Rapid heterosexual spread to women.

Steady rise in prevalence among women since early 1980s

Women are 50% of adult PLWHA worldwide and 60% of adult PLWHA in Africa

HIV continues to be progressively feminized

Women are Particularly Vulnerable to Heterosexual Transmission: Why?

Large mucosal exposure to semen

Biology of the HIV virus

Poverty / Low socio-economic status

• High prevalence of non-consensual sex
• Sex without condom use
• Unknown or high-risk behavior of partners
• Young women with much older partners

Progression of HIV to AIDS in Women

Viral load is lower in women than men but rate of progression to AIDS is similar

HIV-infected women have shorter survival times than men (33% more likely to die than men)

Baseline serum albumin: a strong predictor of 3 year survival

Higher C-reactive protein (>0.4mg/dl): associated with shorter survival

Women-Specific Symptoms of HIV Infection

Vaginal yeast infection

• Persistent and more difficult to treat
• Fluconazole is drug of choice.
• Weekly fluconazole can safely prevent oropharyngeal and vaginal, but not esophageal yeast infection

Bacteria vaginosis, Gonorrhoea, Chlamydia, Trichomoniasis

Herpes simplex virus ulceration

Idiopathic genital ulceration (unique manifestation of HIV)

HPV infection/genital warts

Cervical dysplasia/cervical cancer

PID (more common and more aggressive)

Menstrual irregularities (more likely to be amenorrheic)

With Advent of Potent ARVs:

• The HIV-infected are living longer
• HIV now a manageable chronic illness.
• HIV affected couples desire to have children
• Affected couples require information to make informed reproduction decisions

Sero-discordant Couples; Concerns

• Overall risk of heterosexual transmission is low
• Male to female transmission is significantly higher than the risk of female to male transmission.
• Transmission is increased with:
• Higher plasma viral load in infected partner
• Presence of other STIs in either partner

Concerns with sero-discordant couples

• Risk of HIV transmission to un-infected partner
• HIV transmission to the child
• Cost of assisted reproduction techniques.

Sero-concordant Couples

• Consistent safer sex (condom) advised
• Prevent super-infection, especially with drug- resistant strains
• Prevent infection with other STIs e.g. HCV, HBV
• Prevent new-infection during pregnancy

Suggested Pre-conception Steps

• Disclosure of sero-status
• Practicing safe sex
• Preconception counseling:
• Discuss risk to partner and baby
• Current and future health of infected partner(s)
• HIV testing pre and post-pregnancy
• Absence of an active AIDS-defining illness
• CD4 count >350 and viral load < 50,000 copies/ml
• Patients receiving antiretroviral therapy
• HIV RNA level < 400 copies/ml
• Regimen without teratogenic drugs (Elovirenz, amprenavir)
• Adequate therapy for at least 1 year

Women

• Endocervical swab (ECS) culture, Pap smear, Pelvic USS, Serum FSH < 15MIU/ml, HSG

Men

• Semen analysis

Men and Women

• CBC, LFT, Hepatitis virus screening, pelvic examination
• Full screening for HIV, other STIs and TB.

Assisted Reproduction Techniques

Self-insemination

• Low cost option for sero-discordant couples (woman infected, man un-infected)
• Use of freshly ejaculated semen
• Dispensed by a standard syringe (without the needle) or a disposable plastic Pasteur pipette

Timed Intercourse

• Both partners undergo infertility work-up
• Methods of identifying fertility window: BBT, Calendar calculation, Ovarian follicle tracking by USS, Urine LH and Billings method (cervical and vaginal discharge)
• Gilling-Smith(2000) reported 4% transmission rate in 92 sero-discordant couples. Sero-conversion was restricted only to partners who reported inconsistent condom use outside the 'fertile period’.

Population-based studies of fertility in women with HIV-1 infection in Africa found that pregnancy rates were lower and pregnancy loss was more common in HIV-infected women

Pregnancy does not accelerate decline in CD4 cells

Pregnancy has little to no effect on HIV progression in asymptomatic women or women with early infection.

More rapid progression in women with late stage HIV infection

HIV has little effect on pregnancy in the developed world

Adverse effect in African studies

• Spontaneous abortion
• Intrauterine growth restriction
• Preterm birth
• Low birth weight
• Pneumonia
• UTI
• Ectopics
• PROM
• Infections
• Abruptio placenta
• Still birth

Issues to consider in Pregnancy

Pregnancy may influence infection because of pregnancy related suppression of cellular immunity

CD4 & CD8 percentages are stable during pregnancy

Pregnancy rates among HIV positive women who have not yet developed AIDs are comparable with those among uninfected women. Women with AIDs with opportunistic infection are considered less likely to become pregnant.

No clinically significant changes in pregnancy or postpartum

Overall pregnancy does not seem to accelerate HIV infection.

Mother to Child Transmission (MTCT) of HIV

Over 56,000 children are newly infected with HIV in Nigeria each year

Nigeria alone contributes 30% of global new infant infections through MTCT

In contrast:

• USA & Western Europe - 1000
• Australia & New Zealand 100

Between 15% and 40% of babies born to HIV positive mothers acquire the infection in the absence of intervention.

Key determinants:

• High maternal plasma viral load
• Length of exposure to breast milk

MTCT of HIV can occur

• In-utero [5-10%]
• During labour/delivery [10-20%]
• Through breastfeeding [5-20%]

MTCT of HIV (Kinshasa, DRC)

• In-utero [23%]
• Intrapartum [65%]
• Postpartum [12%]

MTCT of HIV (French collaborative study)

• In-utero, late in pregnancy [35%]
• Around the time of labor [65%]

Factors affecting mother-to-child transmission of HIV

Viral

• Viral load
• Viral genotype and phenotype
• Viral resistance

Maternal

• Maternal Immunological status
• Maternal nutritional status
• Maternal clinical status
• Behavioural factors (Smoking, Alcohol, and Injection drug use)
• HIV infection acquired during pregnancy or breastfeeding
• Genital tract infections (STIs, Chorioamnionitis)

Obstetrical

• Prolonged rupture of membranes (>4 hours)
• Mode of delivery— vaginal delivery is higher risk than CS
• Intrapartum haemorrhage
• Obstetrical procedures
• Chorionic villus sampling
• Amniocentesis
• External cephalic version
• Etc
• Invasive fetal monitoring

Fetal

• Prematurity
• Genetic
• Multiple pregnancy
• Placental malaria

Infant

• Breastfeeding
• Gastrointestinal tract factors
• Immature immune system

Risk Factors for Postnatal Transmission

• Younger maternal age, lower parity
• Maternal sero-conversion during lactation
• Maternal immune status (CD4)
• Plasma and breast milk viral load
• Duration of breastfeeding
• Breast health:
• Mastitis (clinical and subclinical)
• Breast abscess
• Cracked nipples
• Infant factors (oral thrush)
• Pattern infant feeding - exclusive vs mixed

Components of PMTCT (UNGASS)

1. Primary prevention of HIV infection in women of reproductive age
2. Prevention of unintended pregnancies among women infected with HIV
3. Prevention of HIV transmission from women infected with HIV to their babies
4. Provision of treatment, care, and support to women infected with HIV, their infants, and their families

Strategies of PMTCT

Prevention of HIV among women of childbearing age

• Abstinence
• Being faithful
• Condom use
• Safe blood transfusion
• Safety of sharps

Prevention of unintended pregnancy among HIV-positive women

• Family planning counseling and services
• Abortion/post abortion services

Prevention of MTCT

• Universal ANC patronage
• HIV Counseling & testing (opt-out approach)
• Anti-retroviral drug prophylaxis/therapy
• Safe obstetric & delivery practices
• Infant feeding counseling and support

Provision of care & support to HIV-infected women, their infants & families

• Mother/family's HIV care/treatment
• Early infant diagnosis & treatment
• Support for OVC
• Strengthening of social/economic/nutritional support

Prevention of new infections in young women

• Improvement of women's status in society
• Provision of information about HIV/AIDS and its prevention
• Promotion of safer sex (barrier methods)
• Adequate treatment of STIs.

Behavioral interventions

• Reduction in frequency of unprotected sex during pregnancy.
• Reduction in the number of sexual partners during pregnancy.
• Lifestyle changes; avoidance of drug use and smoking in pregnancy.

Therapeutic interventions

• Antiretroviral therapy
• Treatment of STIs.

Obstetric interventions

• Avoidance of invasive/traumatic tests and procedures.
• Caesarean section delivery.

Modification of infant feeding practice

• Formula feeding exclusively [When AFAS- Acceptable, Feasible, Affordable, Sustainable, Safe].
• Breastfeeding exclusively for first 6 months.
• Heat treatment of expressed breast milk
• Avoidance of mixed feeding
• Prophylactic HAART during breastfeeding

Infant therapy

• Antiretroviral prophylaxis.

Specific interventions

• Screen and treat STI in pregnant women
• Use of antiretroviral drugs
• Safe delivery practices
• Safe infant feeding practices

The goal of PMTCT

To prevent the transmission of HIV from mother to child

To mitigate the impact of HIV/AIDS on infected and affected individuals

A PMTCT- plus program

• VCT
• ANC
• Delivery care
• PP care
• Infant care
• Long term follow up

Support services

Support groups

Micro-credit

Home visits

National PMTCT Program

Objective of National PMTCT Program

To reduce the proportion of infants who acquire HIV from their mothers by 50% and to mitigate the impact of the infection on women and their families

National PMTCT Protocol

ANC clinic and side laboratory:

• Group counselling
• Routine offer of HIV testing with options to decline
• Testing algorithm using 2 Rapid tests and a tie breaker to confirm positive cases
• Individual post test counselling

Post test counselling for HIV positive women

• Birth options and other preventive measures
• Counselled on ARV interventions
• Counselled on infant feeding options
• Nneed to deliver in hospital

Post test for HIV Negative

• Counsel on 'window period'
• Consider re-testing in labor
• Offer syndromic STI management
• Importance of partner testing

Pediatric Follow up:

• Infant feeding counseling & support
• Infant immunizations & growth monitoring
• Infant diagnosis (from 6 weeks) and treatment

Post natal Clinic:

• Evaluation of Mom for ARV and refer accordingly
• Family Planning
• Cervical Screening
• Partner testing and referral accordingly

Infant feeding of choice

Breast feeding?

Breast milk substitutes- ????? AFASS

BMS a right issue

Diarrhea vs HIV

Breastfeeding and transmission

There is a greater risk within the first week → months

4-6% risk for week 6→ 6 months

Late breastfeeding is associated with a low continuous rate of transmission of 3.2%/year

Factors associated with transmission

• Low vitamin A levels
• Mastitis
• Low IgA

Challenges of PMTCT

• Poor coverage
• Inadequate supplies
• Poor capacity
• Nil motivation
• Stigma/discrimination
• Service problem
• Unsupervised delivery
• Upgrade of services
• Universal precaution
• Infant feeding
• ARV/adherence
• MTCT plus
• Care of orphan
• Long term follow-up

Recommendations

• Pregnancy is an indication for ARV
• ANC becomes portal of entry
• Combination therapy-gold standard is HAART
• Universal access /PMTCT in ANC
• ARV in continuum of care
• Shared care
• Data management
• Monitoring/evaluation

There is no shame in being HIV+ but there is shame in rejecting the HIV+ patient.

HIV can affect anybody including our friends and relations

HIV+ patients deserve our care, love and support.

—Nelson Mandela

• Limited ability of health system Lack diagnostic techniques for:
• HIV
• Opportunistic infections, STIs
• Viral load
• Surrogate markers for progression of HIV
• Should be jointly managed by HIV Specialist, an obstetrician, midwife and pediatrician
• Early booking
• Screen for Hepatitis B syphilis and common STIs, cervical cytology
• Rest of ANC remains the same

Ante-natal care

• Health education
• Voluntary counselling and testing (VCT)
• Avoid invasive diagnostic procedures
• Watch for telltale signs
• TB, thrush, anemia
• Nutritional support
• Treat malaria
• Fe/FA supplement
• FP

Care in labor and delivery

• Avoid ARM/PROM/fetal scalp blood sampling
• Avoid procedures such as ECV
• Universal precautions should be applied
• Avoid routine episiotomy
• Forceps preferable to vacuum
• Elective C/S beneficial
• Prophylactic antibiotics

Intrapartum

• Elective Caesarean section
• Combined with antiretrovirals
• Double gloving
• Use of blunt needles and tissue holding forceps
• Fetal membranes should be left unruptured
• Avoid invasive procedures
• Amniocentesis
• Fetal scalp electrodes
• Amniotomy
• Peripartum cord blood sampling
• All procedures including assisted delivery increase risk of MTCT
• Early cord clamping and early bathing of the baby

Postpartum Care

• Women should not be isolated
• Universal precautions should be practiced Proper disposal of contaminated sanitary towels, lochia, dressings and drains
• Decontaminate toilet - seats and ward floors with sodium hypochlorite solution
• Postnatal care and counseling for woman and partner on safer sexual practice and appropriate contraceptive plans: condom use.

Recommendations

In pregnant women with confirmed HIV serostatus, initiation of ART for her own health is recommended for all HIV-infected pregnant women with CD4 cell count < 350 cells/mm³, irrespective of WHO clinical staging; and for all HIV infected pregnant women in WHO clinical stage 3 or 4, irrespective of CD4 cell count.

HIV-infected pregnant women in need of ART for their own health should start ART irrespective irrespective of gestational age and continue throughout pregnancy, delivery and thereafter. (Strong recommendation, moderate quality evidence).

All HIV-infected pregnant women who are not in need of ART for their own health require an effective ARV prophylaxis strategy to prevent HIV transmission to the infant. ARV prophylaxis should be started from as early as 14 wweeks gestation (second trimester) or as soon as possible when women present late in pregnancy, in labor or at delivery. (Strong recommendation, low quality evidence).

The HIV exposed infant

All infants born to HIV-infected women should receive daily NVP from birth until 6 weeks of age.

Thereafter, exclusively breastfed infants whose mothers are NOT on HAART should continue receiving daily NVP until one week after stopping breastfeeding. (Strong recommendation, moderate quality evidence).

Co-trimazole and malaria prophylaxis

Routine Co-trim prophylaxis for CD4 350 and below.

Malaria prophylaxis: 3 doses of sulphadoxine-pyrimethamine (Fansidar) from 2nd trimester at least 4 weeks apart.

Patients on Co-trim do not need S-P for malaria prophylaxis during pregnancy.

Cesarean section to reduce perinatl HIV transmission

C/S reduces transmission in women with unknown VL who are not on ART or are receiving only ZDV.

ACOG recommended C/S for pregnant women with VL > 1000 cells/ml near time of delivery.

Unclear whether scheduled C/S offers any benefit to women on ART with VL ≤ 1000 copies/ml, given the low transmission rate.

C/S should be scheduled at 38 weeks, determined by the best clinical estimates.

Complications of C/S somewhat more frequent than in HIV-uninfected women, increased in immunocompromized women.

Breastfeeding and HIV infection

HIV in 60% of milk samples

Breastfeeding of 24 months= additional 16% MTCT rates.

BF reduces long term overall efficacy of short course AZT.

Choice of infant feeding

Exclusive formula feeding

Exclusive breast feeding

Pretoria pasteurization- heat expressed breast milk to 62.5°C

Cow or goat milk

RT have shown a 44% reduction in VT in formula-fed infants.

although many patients chose BMS, they face tremendous opposition in a society that believes breast-milk is best and that something is fundamentally wrong with a woman who does not breastfeed her baby.

Problems of formula feeding

• Diarrhea
• Malnutrition
• Sepsis
• Occasionally, death

Multivitamins resulted in large and significant reductions in the risk of

• Fetal death
• Low birth weight
• Severe prematurity

Significant and sustained improvements in CD4 and CD8 cell counts.