HIV in Pregnancy

1. HIV in Pregnancy Max Brinsmead PhD FRANZCOG May 2011

2. Human Immunodeficiency Virus • HIV is a Lentivirus • A member of the Retrovirus family • Infects helper T cells (CD4), macrophages & mucosal dendritic cells • Depletes CD4 numbers & thereby cell-mediated immunity • Opportunistic infections and/or tumours then begin • This is then known as AIDS • Which untreated is fatal within 12m

3. HIV Infection • Two subtypes of the virus • HIV1 - global • HIV2 – mostly limited to West Africa • This virus is transmitted by… • Blood and blood products • Tissue • Semen • Vaginal fluids • Transplacental • Breast milk • Although found in tears, saliva and urine it is not transmitted by these fluids

4. After exposure to HIV • Incubation period of 2 – 4 weeks • Then an acute CMV-like illness • Fever • Lymphadenopathy • Pharyngitis • Myalgia & malaise • Lasts about 28 days • Median seroconversion time is 22 days • Then Latent Phase of 2 – 20 years depends on: • Host response • Viral factors • Environmental factors • Treatment (if any) • Untreated →typically AIDS within 10 years

5. HIV transmission risk • Female to male 0.04% rate per coital act • Male to female 2-fold higher • But 4 -10fold higher in developing countries • Receptive anal coitus 1.7% rate per act • Condoms reduce the risk by 85% • Circumcision reduces ♀→♂ rate by 50% • Needlestick 0.3% rate per injury • Maternal to Child Transmission (MTCT) with pregnancy, birth & breastfeeding 25 – 48% • >400,000 new cases per year worldwide

6. HIV Diagnosis • Screen by ELISA (very sensitive) • Retest those that are positive in duplicate • The confirmatory test is Western Blot (WB) • or IFA (less commonly done) • Inconclusive WB – repeat after 28 days • Risk of false positive in this 2-step procedure is <1:10,000 • Disease activity is measured by CD4 count • And less commonly by viral load (RNA or DNA) as measured by PCR or TMA • P24 antigen testing is for the virus itself – has very low sensitivity

7. HIV Treatment • Typically only commences when CD4 counts fall below 350 • Optimally comprises triple therapy with HAART • HAART = Highly active antiretroviral therapy • This prolongs latent period by 20 – 50 years • Successful treatment reduces detectable virus to zero over 4 - 6 months • However, this is achieved only 50% of the time because of: • Side effects • Non compliance for financial, psychological or other reasons • Viral drug resistance • In resource-rich settings HAART may start earlier

8. WHO Staging (2005) >15 yrs of Age • Clinical stage 1 • Asymptomatic • Persistent generalized lymphadenopathy • Clinical stage 2 • Weight loss (<10% of presumed or measured body weight) • Recurrent respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis) • Herpes zoster • Recurrent oral ulcerations • Papularpruritic eruptions • Angular cheilitis • Seborrhoeic dermatitis • Fungal finger nail infections

9. WHO Staging (2005) >15 yrs of Age • Clinical stage 3 • Unexplained chronic diarrhoea >1 month • Unexplained persistent fever >1 month) • Weight loss (>10% of presumed or measured body weight) • Oral candidiasis • Oral hairy leukoplakia • Pulmonary TB • Severe infections e.g. pneumonia, empyema, meningitis, bacteraemia, pyomyositis, bone or joint infection • Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

10. WHO Staging (2005) >15 yrs of Age • Clinical Stage 4 • HIV wasting syndrome • Pneumocystis pneumonia • Recurrent pneumonia • Herpes simplex >1 month • Oesophageal candidiasis • Extrapulmonary TB • Kaposi’s sarcoma • CNS toxoplasmosis • HIV encephalopathy

11. WHO Staging (2005) >15 yrs of Age • Stage 4 (with additional tests) • Extrapulmonarycryptococcosis • Disseminated non-TB mycobacteria • Progressive multifocal leukoencephalopathy • Candida of trachea, bronchi or lungs • Cryptosporidiosis • Isosporiasis • Visceral herpes simplex infection • CMV retinitis or any organ other than liver, spleen or lymph nodes) • Any disseminated mycosis e.g. histoplasmosis, coccidiomycosis, penicilliosis • Recurrent non-typhoidal salmonella • Lymphoma (cerebral or B cell non-Hodgkin) • Cervical carcinoma • Visceral Leishmaniasis

12. HIV Treatment in Resource-Poor Areas • Clinically advanced HIV disease • WHO Stage 4 irrespective of the CD4 cell count • WHO Stage 3 + consider using CD4 < 350 to assist decision making • WHO Stage 2 or 1 with CD4 counts < 200

13. Effects of HIV on Pregnancy • Risk of maternal death is increased 6-fold • Concurrent infections including TB • All obstetric causes • Increased risk of poor obstetric outcome • Miscarriage • Stillbirth • Pre term birth • IUGR • Mother to Child transmission (MTC) of HIV • Is the most common means of HIV transmission in the world • Risk is 25 – 50%

14. Risk Factors for Mother to Child Transmission • Primary HIV infection • Repeat testing of high risk individuals may be required • Concurrent infections including TB and STI • High maternal viral load and low CD4 counts • Prolonged rupture of membranes • Vaginal delivery • Fetal trauma during delivery • Breast feeding • High viral load in breast milk • Mastitis

15. HIV Mother to Child Transmission • 80% occurs during labour • Can be reduced by 50% Caesarean section before membranes rupture • But only used where CS is safe in the short and long term • And viral load is >1,000 ml/plasma • Next best option is a single dose of NVP at least 2 hours before delivery. Follow up with AZT + 3TC for one week • Give the baby one shot of NVP when born + AZT for one week • Risk of MTC is then approx. 5% • If mother receives triple therapy from <28w, has elective CS & does not breast feed MTCT is 1-2%

16. Nevirapine Resistance • Single dose Nevirapine (NVP) before delivery is widely used in resource-poor settings to prevent MCT of HIV • But this induces NVP resistance in 12 – 14% of mothers AND babies • So double or triple therapy is preferred • If you can afford it

17. Cochrane on HIV in Pregnancy • All adults with HIV and CD4 count <350 require HAART for life • The best predictor of maternal health and MTCT is plasma viral load. Aim for <500/ml • Risk of teratogenesis in the 1st trimester to be weighed against maternal need for HAART • WHO guidelines now assume benefits exceed risk • Regimens with LPV have an increased risk of prematurity • Regimens with NVP have increased rates of adverse maternal effects • Best regimen is therefore AZT/3TC/ABC followed by dual or triple therapy especially if breastfeeding • MTCT rate after vaginal delivery is then ≈ 12%

18. Current WHO Guidelines • All HIV patients to begin HAART asap • Continue right through VAGINAL DELIVERY • Tail off non-eligible mothers from therapy after they have stopped breast feeding AND • Give the infant oral NVP whilst ever mother is breastfeeding plus one week (up to 12 months) • Mothers eligible to continue triple therapy to continue whilst breast feeding PLUS • Give the neonate 6 weeks of AZT and NVP for as long as the mother is breast feeding • It is hoped that MTC will be 1-2%

19. HOWEVER… All of this presupposes that… All pregnant women will commence antenatal care at <14 weeks gestation All women will have a HIV test High risk women will have a second HIV test There are medical resources to provide optimal therapy All HIV-positive women will take the therapy and give it to their babies as prescribed