# Presentation: 376151

## Prevention of Mother-to-Child HIV Transmission in the U.S. and Globally

**Lynne M. Mofenson, M.D.**
**Pediatric, Adolescent and Maternal AIDS Branch**
**National Institute of Child Health and Human Development**
**National Institutes of Health**
**Department of Health and Human Services**

## Overview

**Perinatal transmission in the U.S.: **
**PACTG 076 - mechanism efficacy**
**Risk factors for transmission in antiretroviral era**
**Transmission in the post-076 era**
**Challenges**
**Perinatal transmission global basis**
**Short-course antiretroviral prophylaxis trials results and relevance to U.S.**
**Challenges**

## Perinatal Transmission in the U.S.

## Perinatal HIV Transmission:  U.S.

**In U.S., ~6,000-7,000 HIV-infected women give birth annually.**
**Prior to 1994, ~25% of infants born to HIV+ mothers became infected. **
**Thus, 1,500-1,750 infants newly infected with HIV were born each year before 1994.**
**More than 16,000 HIV-infected children born in the U.S. since the beginning of the epidemic.**
**	**

## PACTG 076 AZT Regimen Targeted Multiple Potential Time Points of Transmission

| Pregnancy | Labor/Delivery | Infant |
| --- | --- | --- |
|  |  |  |
| AZT 100 mg 
5 times daily | AZT IV 2 mg/kg 
1 mg/kg/hr  | 2 mg/kg q 6 hr 
x 6 weeks |
|  |  |  |
| TARGET: 
In Utero | TARGET: 
Intrapartum  | TARGET: Postpartum |
|  |  |  |
| 67% Reduction in the Risk of Transmission                     Placebo arm:  25.5%
                        AZT arm:           8.3% |  |  |

## How Did the PACTG 076 AZT Regimen Lower Perinatal HIV Transmission?

**Effect on viral load:  ****In PACTG 076, change in HIV RNA accounted for only 17% of observed AZT efficacy ****(*****Sperling et al. NEJM 1996;335:1621-9*****)****.**
**Two other important mechanisms through which AZT reduces transmission:**
**Pre-exposure prophylaxis**** of infant (through transplacental AZT passage).**
**Post-exposure prophylaxis**** of infant (through continued AZT administration to the infant after birth).**

## How Does AZT Lower Perinatal Transmission? Effect of AZT on Viral Load in PACTG 076 Sperling RS et al. NEJM 1996;335:1621-9

| Characteristic (AZT arm) | PACTG 076 |
| --- | --- |
|   Median Entry RNA | 5,660  |
|   Median Duration AZT | 26 wks |
|   Median change entry-delivery | 0.28 log |
|   Proportion of AZT efficacy                    explained by:
  RNA at delivery
  Change RNA entry-delivery | 

11%
17% |

## AZT Lowers Transmission Even in HIV-Infected Women with Very Low Viral LoadIoannidis JPA et al.  J Infect Dis 2001;183

**Meta-analysis of 7 prospective cohorts/trials.**
**44 cases transmission among 1,202 HIV+ women with delivery HIV RNA <1,000.**
**Transmission differed by receipt of AZT:**
**Mothers receiving AZT: ****8/834, 1.0%**
**Mothers not receiving AZT: ****36/368, 9.8%**
**Multivariate analysis (adjusting for maternal CD4 count, mode delivery and infant birth weight), AZT independently reduced transmission.**
**Data show importance of infant pre- and post-exposure prophylaxis in addition to lowering maternal viral load as mechanism prevention.**

## Importance of the Infant Pre- and Post-Exposure Prophylaxis Component of PACTG 076 RegimenWade N et al.  N Engl J Med 1999;339:1409

**AP+IP+PP   IP+PP     PP****<24 hr****  PP****>48 hr****  No AZT**

**Even When No Maternal AZT Received, Infant AZT **
**Started Within 24 Hours Reduces Transmission**

## Why Might Pre/Post-Exposure Prophylaxis Be Important?Amount of Cell-Free and Cell-Associated HIV in Cervicovaginal Canal is Associated with Transmission

***Chuachoowong R et al.  J Infect Dis 2000;181:99-106***** **
**Quantified CVL HIV RNA at 38 weeks gestation in 310 women in Thai short-course AZT trial.**
**Presence CVL RNA associated with 3.4-fold increase in transmission; effect independent of plasma RNA, and greatest when plasma RNA low.**
**AP AZT was associated with median 0.8 log decrease in HIV RNA in CVL.**
***Tuomala RE et al.  J Infect Dis 2003;187:375-84***
**Assessed cell-associated HIV DNA in CVL in 78 women receiving antiretroviral therapy (65% AZT alone, 33% combination therapy).**
**Detection/titer of CVL DNA associated with transmission; 2.3-fold increase for each 1 log increase DNA.**

## Infant Exposure to HIV in Vaginal Secretions:

**Potential Mechanisms of HIV-1 Transmission**
**Through Intestinal Mucosa of Infant**

##      63%	

**INTRA**

**POST**

**% Efficacy**
_**  **__**at 6 Wk**__**	**_
**     ****63%****	**
**     ****42%****	****	**
**       ****0%****	****	**

**INTRA**

**INTRA**

**POST**

**PLACEBO**

**PETRA Study of AZT/3TC Prophylaxis:**
**Pre-Exposure Prophylaxis Alone is Ineffective**
***Petra Study Team.  Lancet 2002;359:1178-86***

**36 **
**wks**

**1 wk mom**
**& baby**

## Risk Factors for Transmission

**In Women/Infants in **
**Post- PACTG 076 Era:**
**Viral Load**
**Type of Antiretroviral Therapy**
**Mode of Delivery**

##  Delivery Plasma HIV RNA Level is Associated with Perinatal Transmission

**Women & Infants Transmission Study, 1990-1999*****Cooper E et al.  JAIDS 2002;29:484-94***** **

##  More Potent Antiretroviral Regimens Are Associated with Lower Perinatal Transmission 

**Women & Infants Transmission Study, 1990-1999*****Cooper E et al.  JAIDS 2002;29:484-94***** **

## Slide 16

## Elective Cesarean Delivery Reduces Transmission When PACTG 076 AZT Regimen is GivenThe International Perinatal HIV Grp.  N Engl J Med 1999;340:977-87

**Addition of an intrapartum intervention further reduces **
**perinatal transmission in face of AZT prophylaxis**

**Meta-analysis**
**8,533 women **
**from 15 cohorts**

## Activities in U.S. Following the  Results of  PACTG 076

**Feb 1994:**** PACTG 076 results announced**
**Aug 1994:**** U.S. Public Health Service guidelines for use AZT to prevent transmission published.**
**July 1995:****  U.S. Public Health Service guidelines for prenatal HIV counseling and testing.**
**Periodic updates to guidelines when new information becomes available:**
**Latest update prophylaxis guidelines: Nov 2002**
**Latest update testing guidelines:  Nov 2001**

## Current USPHS Guidelines for Prevention of Mother-to-Child Transmission

**Maternal plasma HIV RNA >1,000: **
**HAART**
**Elective C/S if >1,000 near delivery**
**Maternal plasma HIV RNA **_**<**_**1,000:**
**HAART or use of PACTG 076 AZT alone**
**No treatment prior to labor:**
**Intrapartum-postpartum AZT; AZT/3TC; nevirapine; or AZT/nevirapine**
**No treatment prior to or during labor:**
**Infant prophylaxis for 6 weeks with combination regimen or AZT alone**

## Maternal Antiretroviral Use During Pregnancy at PACTG Sites,1998-2000

**Data from PACTG 367, N = 1,527 **

## Increasing Rates of Cesarean Delivery Among HIV-Infected Women in U.S., 1994-2000 Pediatric Spectrum of Disease, CDC

**N=6,467**

## Mother to Child HIV Transmission in the U.S. Over Time

## Incidence of Perinatally-Acquired AIDS United States, 1985-2000*

- <date/time>

**Incidence of Perinatally-Acquired AIDS**** United States, 1985-2000***

*** Reported through December 2000**

**500**
**400**
**300**
**200**
**100**

**85    86    87    88   89   90   91   92   93   94   95   96    97    98    99    00**

## Progress on Reducing Mother-to-Child HIV Transmission in the U.S.

**Mother to child transmission has been reduced to <2% in the U.S.**
**Number of infected infants born each year in U.S. has decreased from 2,000 before 1994 to under 300-400 currently.**
**Reduction transmission secondary to:**
**Enhanced prenatal HIV counseling and testing.**
**Recognition of the importance of viral load in transmission, and increase in use of HAART by pregnant women.**
**Increase in elective cesarean delivery.**

## Challenges Remain

**Remaining significant barriers to elimination of perinatal HIV in U.S.:**
**Continued HIV transmission to women, especially  adolescents, who have high rates of unintended pregnancy.**
**Lack of prenatal care, particularly in women who are illicit drug users (15% of HIV-infected women lack prenatal care).**
**Failure to identify HIV infection during pregnancy.**
**Antiretroviral drug resistance.**

## Antiretroviral Resistance in Adults with New HIV Infection, U.S./Canada

**Frequency of antiretroviral resistance mutations among newly infected persons increasing:**
***Grant et al. JAMA 2002;288:181-8 (San Francisco)***
**From 1996-97 to 2000-01(N=225)**
**NRTI: 25% to 21%**
**NNRTI: 0% to 13%**
**PI: 3% to 8%**
**Resistance correlated with viral response**
***Little et al. NEJM 2002;347:385-94 (10 cities)***
**From 1995-98 to 1998-2000 (N=377)**
**Any:  8% to 23%**
**Multidrug: 4% to 10%**
** **
**more pregnant women are now treatment-experienced.**

## More HIV-Infected Pregnant Women are Antiretroviral-Experienced and Have ARV Resistance: Resistance in Women in PACTG 316*Cunningham C et al.  J Infect Dis 2002:186:181-8

***23% on AZT alone; Combo no PI 36%; Combo PI 41%**

## Impact of Antiretroviral Resistance on Prevention of Perinatal Transmission

***Mofenson L et al.  AIDS Conf 2002***
**PACTG 185 (86% AZT, 14% combo NRTI), case-control study of 24 transmitters, 72 controls**
**At delivery:**** **
**AZT resistance: 25% transmitters vs 11% controls (p=0.14) **
**Any NRTI resistance: 46% transmitters, 25% controls (p=0.15)**
***Welles S et al.  AIDS 2000;14:253-71***
**WITS, case-control study of 142 pregnant women **
**Prevalence AZT resistance, 24%**
**Multivariate analysis, genotypic AZT resistance associated with 5.1-fold increased risk transmission**
**At present, most cases of antiretroviral failure with transmission despite antiretroviral prophylaxis are not due to drug resistance, but this may change as resistance becomes more frequent.**

## Perinatal Transmission Global Picture

## Perinatal HIV Transmission:  Global12

**Globally, >2 million HIV-infected women give birth annually, most in resource-poor countries, where regimens used in US are too complex and expensive to use.**
**Transmission rates in breastfeeding women without antiretroviral prophylaxis are between 25-40%. **
**About 2,000 children become infected daily; in 2002, an estimated 800,000 infants were newly infected with HIV.**
**An estimated 3.2 million children were living with HIV in 2002.**

## Importance of Breastfeeding Postnatal Transmission:Timing of Mother-to-Child HIV Transmission with Breastfeeding and No Antiretroviral Prophylaxis

**0%**

**20%**

**40%**

**60%**

**80%**

**100%**

**Early Antenatal**
**(<36 wks)**

**Late Antenatal**
**(36 wks to labor)**

**Labor and Delivery**

**Late Postpartum**
**(6-24 months)**

**Early Postpartum**
**(0-6 months)**

**Proportion of infections**

## International Perinatal HIV Trials

**Following PACTG 076:**
**Need to develop shorter, less expensive regimens more applicable to resource-limited settings.**
**Studies first focused on modifications of AZT-alone prophylactic regimens.**
**Studies also explored whether short-course combination regimens might have improved efficacy.**
**Studies asked if similar efficacy to combination could be achieved with alternative drugs that were less expensive and could be used in simple regimens.**

## Completed Trials: Focused on Prevention AP/IP Transmission

**3d to**
**1 wk**

** ****36 **
**wks**

** ****14**
**wks**

**  ****6 **
**wks**

_**IP**_

**076**

**Thai (Harvard)**

**Thai (Harvard), BMS**

**IvC (ANRS), PETRA, Thai (Harvard)**

**Thai (CDC), IvC (CDC)**

**PETRA, 012, SAINT**

**PETRA**

_**AP**_

_**PP**_** ****(baby, mother or both)**

**Thai (Harvard)**

**28**
**wks**

**NonBF**

**NonBF**

**NonBF**

**NonBF**

**BF/NonBF**

**NonBF/BF**

**BF**

**BF**

**AP:**** Minimum duration?**
**       ****Is it needed?**

**PP:**** Minimal duration?**
**       ****Is it needed?**

**IP:**** Work **
**     ****alone?**

## Short-Course AZT Studies

**Short-course AZT prophylaxis is effective.**
**Longer (28 weeks) antepartum treatment is more effective than shorter (36 weeks) antepartum therapy, showing that a significant proportion of *****in utero***** infection occurs between 28 and 36 weeks.**
**Efficacy of prophylaxis is diminished by breastfeeding, but still persists at 24 months with short-course AZT. **

## Short-Course AZT Prophylaxis: Efficacy in 

**36 wks**

**INTRA**

**INTRA**

**Short-Course AZT Prophylaxis: Efficacy in **
**Formula-Fed vs Breast-Fed Infants**

**PRENATAL**
**36 wk**

**% Efficacy**
**  **_**at 6 Mos**_
**     **
**50%**
**37%**
**     **

**Thailand ****Formula Feeding**

**Ivory Coast ****Breast**** ****Feeding**

**% Efficacy**
**  **_**at 24 Mos**_
**50%**
**26%**

***Placebo-controlled trials***

***Shaffer et al.  Lancet 1999;353:773-80***

***Wiktor et al.  Lancet 1999;353:781-5***

## Short-Course AZT Prophylaxis, Formula-Fed Infants: Duration of AP/PP Therapy Lallemant M et al.  N Engl J Med 2000;343:982-91 	

**Most Effective**
**(Tx  4% [vs SS])**

**Least Effective **
**(Tx 11%)**

**Intermediate**
**(Tx  5%)**

**Intermediate**
**(Tx  9%)**

**Long-**
**Long**

**Long-**
**Short**

**Short-**
**Long**

**Short-**
**Short**

_**AP**_

_**IP**_

_**PP Infant**_

**28 wk**

**36 wk**

**3 d**

**6 wk**

## Long Better than Short Maternal Antepartum Therapy for Preventing In Utero Transmission Lallemant M et al.  N Engl J Med 2000;343:982-91

**AP: 28 wks**

**AP: 36 wks**

**P<0.001**

**1.6%**

**5.1%**

## Short-Course Combination Regimens

**After short-course AZT found effective, researchers then asked if short-course combination regimens would be more effective than AZT alone.**
**AZT/3TC prophylaxis appears more effective than AZT alone.**
**3-part AP/IP/PP drug prophylaxis is more effective than IP/PP alone.**
**IP-only not effective, showing importance of post-exposure prophylaxis component.**
**Efficacy diminished by breastfeeding and did not persist at 18 mos for the IP/PP AZT/3TC regimen.**

## AZT/3TC Better than AZT Alone:Open-Label AZT/3TC Perinatal Prophylaxis Studies in Formula-Fed Populations

** ****14**
**wks**

**  ****6 **
**wks**

_**IP**_

_**AP**_

_**PP (baby)**_

**32**
**wks**

**France**
**ANRS 075**
***Mandelbrot***
***JAMA 2001***

**Thailand**
***Chaisilwattana****** ***
***CID 2002***

_**Tx**_

**1.6%**

**2.8% **

**vs AZT only**
**1994-1996 hx control, 6.8%**

**vs AZT only   **
**1994-1996**
**hx control, 11.7%**

**AZT**

**AZT plus 3TC**

**076 Backbone**

**Short AZT Backbone**

**34 **
**wks**

**4 **
**wks**

## % Efficacy

**INTRA**

**POST**

**% Efficacy**
_**6 Wk**_**	**_**18 Mo**_
**63%****	****	****32%**
**42%****	****	****18%**
**0%****	****	****0%**

**INTRA**

**INTRA**

**POST**

**PLACEBO**

**AZT/3TC Prophylaxis in Breast-Fed Infants**
***Petra Study Team.  Lancet 2002;359:1178-86***

**36 **
**wks**

**1 wk mom**
**& baby**

## Alternative Prophylaxis Regimens

**Research asked whether alternative drugs (like nevirapine) might provide efficacy similar to short combination regimens.**
**When only IP/PP prophylaxis is given, single-dose NVP is superior to IP/PP AZT alone, and similar to IP/PP AZT/3TC.  **
**Efficacy diminished by breastfeeding, but  while 2-part AZT/3TC was not effective at 18 months, NVP retained efficacy. **
**Addition of single-dose NVP to short-course AZT appears to improve efficacy.**
**However, adding NVP to standard regimens used in U.S. does not offer additional benefit.**

##               Efficacy  

**POST**

_**% Transmission**_
**     **_**14-16 Wks**_**   **_**18 Mos**_** **
**      ****13.1%     15.7%**
**      **
**       ****25.1%     25.8% **
**              **_***Efficacy***_***  ***
***       ******47%******	******        41%***

**INTRA**

**POST**

**Alternative Antiretrovirals: Single-Dose Nevirapine vs Ultra-Short AZT - HIVNET 012**
***Guay L et al.  Lancet 1999;354:795-802***

**Nevirapine**

**Ultra-Short**
**AZT**

**2 mg/kg x1**

**200 mg x1**

**4 mg/kg bid **
**x1 wk**

**300 mg **
**q 3 hr**

**versus**

**Breastfed Infants**

##     7.0%    5.7% (2.0-5.3)

**POST**

_**% Transmission**_
**   **_**Birth**_**    **_**Btn Birth-8 Wks**_
_** **_
**    ****7.0%    5.7% ****(2.0-5.3)**
**  **
**    *****Overall, 8 wks:  12.3%***
**    ****5.9%    3.6% ****(3.7-7.8)**
**    **
***Overall, 8 wks:  9.3%***
***(Overall: p=0.11)***

**INTRA**

**POST**

**Comparison of IP/PP Regimens: Single-Dose **
**Nevirapine vs PETRA AZT/3TC - SAINT**
***Moodley D et al. JID 2003;187:725-35***

**Nevirapine**
**(variant of**
**HIVNET 012)**

**AZT/3TC**
**(PETRA)**

**Mom 200 mg x1**
**Baby 2 mg/kg x1**

**200 mg x1**

**Mom & baby**
**x1 wk**

**Q 3 hr**

**versus**

## Does the Addition of Single Dose NVP to Short-Course AZT Improve Efficacy?

**28 wk**

**1 wk**

**oral**

**NVP**

** ****NVP**

**PL**

**PL**

**PL**

**NVP**

**oral**

**1 wk**

**36 wk**

**NVP**

**NVP**

_***Lallemant M et al. 2002 AIDS Conf, Barcelona  Abs LBOr22***_

**DSMB stopped**
**AZT alone (arm 3)**
**@ interim analysis**
**due to significantly**
**higher transmission**

**Arm 1 -**

**Arm 2 - **

**Arm 3 -**

_***F Dabis F et al. 2002 AIDS Conf, Barcelona  Abs ThOrD1428***_

**AZT**

**AZT**

**Plus:**

**Transmission 7% **
**compared to 13%  **
**historical control AZT **
**alone ****(95% breastfed)**** **

**50% breastfed**

**Formula fed**

## Single-Dose NVP Does Not Improve Efficacy of Longer or More Complex ARV RegimensDorenbaum A et al.  JAMA 2002;288:189-98

**Women receiving**
**ARV during **
**pregnancy**

**Continue**
**ARV**

**AZT Perinatal**
**Prophylaxis**

**200 mg**
**dose of NVP**
**vs**
**NVP Placebo**

**2 mg/kg **
**dose of NVP**
**@ 48-72 hr**
**vs**
**NVP Placebo**

**Transmission**
_**Rates**_

_**Pregnancy**_**          **_**Labor**_**        **_**Newborn**_**  ****	**

**1.4%**
**(95% CI, 1-3%)**
**1.6%**
**(95% CI, 1-3%)**

**Randomize,**
**stratified by:**
**1) AP ARV **
**(no, mono, **
**combo)**
**2) Entry CD4**

## Infant Prophylaxis

**Many women may not present until in labor and only infant prophylaxis may be possible.**
**Epidemiologic data suggest infant AZT for 6 weeks after birth reduces transmission.**
**Infant prophylaxis must begin within 24-48 hours after birth to be effective when the mother has not received AP/IP drug.**
**Preliminary data suggest: **
**Single dose NVP given to the infant at birth may have efficacy similar to AZT.**
**Single dose NVP plus AZT may have better efficacy than NVP alone if mother hasn’t received single dose IP NVP.**

## Preliminary Data: Infant Post-Exposure Prophylaxis Trials (South Africa, Malawi; ongoing)

_***Gray G. 2002 AIDS Conf, Barcelona  Abs LBOr13 ***_*******

**NB NVP**

**AZT 6 wk**

**7%**
**11%**

*** Problem: 25% loss to follow-up between birth-6 wks**

_***Taha T. 2002 AIDS Conf, Barcelona  Abs ThOrD1427; ThPpD2146 ***_*******

**NB NVP**

**NB NVP**

**NB NVP**

**NB NVP**

**AZT 1 wk**

**AZT 1 wk**

**IP NVP**

**22%**
**14%**

**14%**
**18%**

**IP NVP**

**Stratify:  ****Late **
**                 *****vs***** **
**               ****Early**
**            ****Presenter**

## Is Combination Better than Standard 6 Wk AZT Post-Exposure Prophylaxis in Formula-Fed Infants?

**AZT x 6 wks**

**AZT x 6 wks**

**AZT x 6 wks**

**NVP birth, 72, 168 hr**

**3TC/NFV x 2 wks**

**IV AZT***

**IV AZT***

**IV AZT***

**Infant**

**Post-Exposure Infant Prophylaxis (PEPI)**
**NICHD/HPTN 040 Trial (Brazil, U.S.)**

****If mom diagnosed in time for IP prophylaxis***

## Current/Planned International Perinatal TrialsInfant or Maternal Antiretroviral Prophylaxis to Reduce Postnatal Breast Milk HIV Transmission

## Design of Ongoing/Planned Infant Prophylaxis Trials

**36 **
**wks**

** **

**  ****6 **
**wks**

_**IP**_

**Botswana **

**Ethiopia/India**

**DITRAME+1**

_**AP**_

_**PP -- Infant**_

**HPTN 046**

**34 **
**wks**

**1 **
**wk**

** ****6 **
**mo**

**SIMBA/MITRA**

**Thai (Harvard)**

**Zambia (Harvard)/SA/**
**HIVNET 024/Uganda**

**Malawi (CDC/NICHD)**

**  ****Malawi (ongoing)**

**28 **
**wks**

**AP: Optimal duration?**
**       ****Is it needed?**

**PP: Optimal duration?**
**       ****Will it work alone?**
**       ****What drug? Is combo better?**
**       ****Exclusive BF, type weaning?**

**14 **
**wks**

**S. Africa/Brazil**

## Infant Prophylaxis Trials:  A Variety of Regimens/Durations Under Study

| Antepartum
(28, 34, 36 wks) | Intrapartum
(oral) | Infant Postpartum
(1, 6, 14 wks,6 mos) |
| --- | --- | --- |
| None | AZT alone | AZT |
| AZT | NVP x1 | NVP |
| AZT/3TC | AZT + NVP x1 | 3TC |
| AZT/ddI | AZT/3TC + NVP x1 | AZT + NVP |
|  | AZT/ddI + NVP x1 | AZT/3TC/NFV |
|  |  | Exclusive BF + type weaning |

## Design of Maternal HAART Prophylaxis Trials

** **

**  ****6 **
**mos**

_**IP**_

**Kenya (CDC) **
**open label**

_**AP**_

_**PP Mother **_

**34-36 **
**wks**

**Botswana **
**(Harvard/EGPAF)**
**open label**

**Malawi (CDC/UNC)**

**Multisite Africa**
**(WHO)**

**PP maternal **
_**regimen**_

**AZT/3TC/NVP vs **
**Baby NVP x 6 mos vs NVP x1 **
**+- multivits**

**AZT/3TC/NVP vs**
**AP/IP AZT/NVP x1 + **
**Baby AZT x1 wk + **
**NVP x1**

**AZT/3TC/NVP**

**AZT/3TC/NVP**

**In randomized studies, CD4 <200 all get HAART, **
**CD4 >200 or 200-500 are randomized**

## Progress and Challenges inReducing Mother-to-Child HIV Transmission on a Global Basis

**Shorter, less expensive regimens than PACTG 076 have been found to be effective in reducing *****in utero***** and intrapartum transmission by 41-63%.**
**Although breastfeeding decreases the overall efficacy, most trials still show a significant decrement at 18-24 months.**
**New approaches, including infant or maternal prophylaxis are targeted at reducing postnatal transmission.**
**Implementation of known effective regimens is now key.**