Focusing Attention on Therapy Adherence and Retention Among Women Diagnosed With HIV During Pregnancy

Kara Wools-Kaloustian

Disclosures

Future Virology. 2014;9(7):621-623. 

While acquisition of HIV by children has declined by 35% since 2009, in 2013 260,000 children acquired HIV, the vast majority of whom resided in sub-Saharan Africa.[1] These new infections in children are primarily acquired from their mothers during pregnancy, delivery or through breast feeding. In the absence of effective antiretroviral prophylaxis, maternal-to-child transmission rates are 14–48%, with the higher transmission rates reported from sub-Saharan Africa thought to be primarily related to breast feeding practices.[2] We know that with combined interventions that include the use of antiretrovirals and avoidance of breast feeding HIV transmission rates can be reduced to as low as 0.46% in resource-replete settings.[3]

In sub-Saharan Africa and other resource-constrained settings, avoidance of breast feeding presents a significant health risk for the child, and so alternative approaches that include the provision of maternal and/or infant antiretrovirals through the breast feeding period have been utilized and resulted in transmission rates of 1–5% at 6 months.[4,5–7] The implementation of prevention of mother-to-child transmission (PMTCT) strategies that include targeted maternal ART is complex and requires multiple steps including: maternal HIV-testing, assessment of ART eligibility (requires CD4 testing), initiation of maternal antiretrovirals, maternal adherence to antiretrovirals in the antepartum and peripartum period, mother and/or infant adherence to antiretrovirals during breast feeding, as well as linkage of the infant to a healthcare facility for early infant diagnosis and follow-up testing after termination of breast feeding.[7] Drop-out between the steps in the PMTCT cascade has been a significant challenge in resource-constrained settings managing large numbers of HIV-infected pregnant women.

In 2011, in an attempt to increase the proportion of HIV-infected pregnant women receiving antiretroviral therapy, in a country with high fertility rates, Malawi conceived and adopted a PMTCT approach called Option B+.[8] This approach advocates the initiation of lifelong ART for all HIV-infected pregnant women regardless of clinical or immunologic status. While this simplifies transition from the HIV testing step to the ART initiation step within the PMTCT cascade, it is unclear what impact this approach will have on ART adherence rates in this population. This is a key issue as incomplete or intermittent adherence would put the current pregnancy as well as subsequent pregnancies at risk for transmission of resistant virus.[9] The 2013 WHO guidelines advocate the use of an NNRTI-based regimen (efavirenz or nevaripine [NVP]) with efavirenz being preferred.[10] Although reported viral suppression rates for NNRTIs vary between studies, adherence levels of 80–89% have been associated with viral suppression rates of 60–94%.[11]

A recent meta-analysis of peri- and post-partum antiretroviral adherence, which included single-dose, short-course, and full ART regimens, found that only 73.5% of women achieved adherence rates of equal to or greater than 80%.[12] This meta-analysis also found that higher adherence rates were achieved during the pre-partum (75.7%) compared with the post-partum period (53.0%), and that women receiving ART had significantly lower levels of adherence (63.5%) than those receiving a single-dose NVP regimen (78.6%). Adherence levels must be evaluated against the retention in care background of a typical PMTCT program, as retention in these programs has been problematic in many regions in sub-Saharan Africa. For example, the B+ program in Malawi, although it has succeeded in significantly increasing the number of women initiating ART during pregnancy and breastfeeding, has a 6-month retention of 82%, and in a Kenyan PMTCT program utilizing a B+ like approach, only 77.%% of pregnant women remained engaged in care until delivery.[13,14] A South African study reported 1-year retention rates of 74.8% in pregnant women initiating ART and found no difference in retention rates between those with CD4 counts ≤200 cells/µl compared with women with 201–350 cells/µl.[15] Taking into account both medication adherence and retention issues, it is possible that only 50% of women initiating ART as part of PMTCT are achieving optimal adherence.

Although these data are concerning, they should not be surprising to healthcare providers and program managers. Consider for a moment the fact that pregnant women are by definition in the midst of significant physiological, emotional and social changes prior to any consideration of HIV testing and its subsequent consequences.[16] Also ponder that some of these physiologic changes lead to nausea, vomiting and esphogeal reflux, often making consumption of medication difficult. In order to accept and adhere to antiretrovirals, a pregnant women testing HIV positive, in a condensed time frame, must process and accept this HIV diagnosis, which has substantial negative implications for her health, economic and social status.[17]

To further complicate this process, the majority of HIV-infected pregnant women reside in parts of the world where taking life-long medications for chronic conditions is a relatively new concept.[18] In cramped living conditions it is difficult to take medications without the knowledge of other individuals residing within the household. As such, it is not unexpected that disclosure of HIV status has been linked to higher antiretroviral adherence levels in some studies.[19] Unfortunately disclosure rates for HIV infected women in sub-Saharan Africa tended to be low, with most studies reporting disclosure rates of <50% during the first 1–2 years after diagnosis.[17] Reported barriers to disclosure include concerns about abandonment, domestic violence, accusations of infidelity and stigma.

While Option B+, use of lifelong ART for all pregnant and breastfeeding women, represents one step in toward addressing leakage within the PMTCT cascade, increased access to antiretrovirals does not ensure acceptance or adherence to either clinic visits or medication. In order to meet the UNAIDS goal of elimination of new HIV infection in children by 2015 we will need to increase our efforts to identify and understand the complex physical, social and psychological factors that impact the lives of HIV-pregnant women and consequently influence retention and adherence, as well as develop innovative interventions to address the factors that are identified as barriers.[20] This should be done in concert with the implementation of promising programmatic adaptations that increase access to ART such as integration of ART services into maternal child health clinics and the adoption of Option B+.[21]

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