UNMET NEEDS OF HIGH-RISK MOTHERS REDUCE SUCCESS OF ANTIRETROVIRAL TREATMENT IN HIV-INFECTED INFANTS

Abstract

In the era of effective PMTCT, the same psychosocio-economic factors that predispose to mother-to-child transmission also substantially increase the likelihood of antiretroviral therapy (ART) failure in infected infants. For HIV-infected infants to benefit from early infant diagnosis and treatment initiation, into which much funding and effort is now invested, it is vital that these unmet needs of high-risk mothers are urgently attended to. From an ongoing study of early infant diagnosis and treatment following in utero transmission in KwaZulu-Natal, South Africa, we describe four cases to highlight these challenges facing transmitting mothers that contribute to treatment failure in the infants.

Effective prevention of mother-to-child transmission (PMTCT) programs have dramatically reduced new pediatric infections, and increasing antiretroviral therapy (ART) access has substantially improved outcomes in infected children^1–3. However, unmet needs persist in pediatric HIV infection⁴. In an ongoing study of early infant diagnosis and ART initiation following in utero transmission in KwaZulu-Natal, South Africa, we observe that the same factors predisposing to MTCT in the current era of effective prevention are precisely those that militate against the success of antiretroviral treatment for infected infants. Four cases are described below to illustrate that the unmet needs of the high-risk mother urgently have to be addressed in order to achieve successful treatment of the infected child.

M1 is a 21 year old mother who herself became HIV-infected as a result of MTCT. M1’s mother demised from HIV-related conditions when M1 was 10 years of age. Disclosure of M1’s HIV status was at 13 years. Thereafter, adherence became problematic as she navigated adolescence without parental support. Now living with her partner’s family, she feels unable to disclose her HIV status. She had her first child at 18 years of age, who died at 12 months, HIV status unknown. Two years later, she had a second child who was diagnosed HIV-infected on the day of birth and ART was initiated at 20 hours of age. Giving ART to her baby was erratic because M1 needed to hide the medication. Viral load in the child became undetectable at 2 months of age but rebounded the following month and has remained unstable since.

M2 is a 17 year old whose first child was born 2 years previously with intra-uterine HIV infection. M2 recently delivered her second baby at 28 weeks gestation after a pregnancy without antenatal care. This child is also HIV-infected. M2 lives at home with her parents, having left secondary school prematurely. M2 has suffered from substance abuse and partner violence. M2 and the first HIV-infected child remain virologically unsuppressed, although the first child achieved an undetectable viral load at 2 months of age. The viral load of the second child is not known.

M3 is a 30 year old, married woman. She and her husband both attended secondary education and are both employed. M3 was first tested HIV-positive at 28 weeks gestation and was told that taking ART would prevent the possibility of her transmitting the virus to her child. The baby’s initial HIV test was indeterminate and viral load was undetectable. Repeat testing confirmed the baby was HIV-infected. When told that the baby was infected, M3 said she had lost faith in ART, since she denied missing any doses during pregnancy. Subsequently, M3 has struggled to take her own therapy consistently or to administer ART to the infant and virus remains unsuppressed in both mother and child.

M4 is a 22 year old mother who was orphaned in early childhood. Because of domestic violence at the hands of her extended family, she lived in a home of safety. ART was defaulted prior to and during pregnancy due to non-disclosure issues. She delivered a 1.4kg baby at 29 weeks gestation. The baby had an extended hospital stay because of multiple medical conditions associated with prematurity. The prolonged hospital stay provided opportunity for intervention including social worker involvement, allowing reconciliation between M4 and her partner’s family and disclosure of her HIV diagnosis to them. The baby inititated ART within the first 48hrs of life and reached an undetectable viral load at 1 month of age. Both mother and baby have remained virologically suppressed to date without viral blips or rebound.

These four case studies illustrate several general features we have observed among the study cohort of in utero infected infants and their mothers as a whole. In many cases the same factors that have destabilised the lives of mothers, and that contribute to HIV transmission, are those that interfere with effective treatment of HIV in the infants. By contrast, in the same setting in KwaZulu-Natal, South Africa, but 15 years ago, in the era prior to effective PMTCT, ART adherence levels of ≥95% and virological suppression rates of 100% were seen in infants at one year post ART⁵. At that time, MTCT rates were high² and there was no self-selection for non-adherence in those mothers.

The psychosocio-economic factors displayed in Table 1 play a critical role in determining ART adherence and thus virologic suppression in mother and child. Central among these is non-disclosure of HIV status to household members, as noted in other African studies^4,6. The struggle for survival experienced by many of these mothers takes priority over risking disclosure of HIV status, since in many cases the mother is entirely dependent on her partner for the basic needs of food and housing. Striking a balance between these two fundamental life issues of caring for her HIV-infected child and of her own survival requires an open dialogue between health care providers and receivers of health care.

Table 1.

Psychosocio-economic and clinical factors influencing antiretroviral treatment outcome in four mother-child pairs following in utero HIV transmission.

PATIENT FEATURES	CASE 1	CASE 2	CASE 3	CASE 4
MOTHER
Psychosocial/family	Loss of mother in childhood, lack of family support Dependence on partner and partner’s family for accommodation Non-disclosure to partner/partner’s family First pregnancy at 17yrs	Left school prematurely - lack of education & life skills Substance abuse Partner violence First child at age 15yrs 2nd child at age 17yrs	Stable, married, well-educated; both she and husband employed The ability of ART adherence to reduce the risk of MTCT was not fully explained	Orphaned from early childhood, lived in home of safety Domestic violence in extended family Non-disclosure to extended family prior to delivery
Clinical	Chronic HIV infection from birth Declining CD4, persistent viremia	No antenatal care Viremia unsuppressed	Viral load 350 c/ml at delivery; latest viral load 9,700 c/ml	Viral load 330,000 c/ml at delivery; latest viral load <20 c/ml
CHILD
Psychosocial/family	Sibling died at 12m age Maternal nondisclosure, nonadherence	Two children with HIV infection Maternal nondisclosure, nonadherence	Mother has lost faith in ART Non-adherence despite disclosure	Mother reconciled with her family, facilitating disclosure and ART adherence
Clinical	Persistent viremia	Younger sibling premature 28 weeks gestation Persistent viremia	Initial viral load <100 c/ml; at 2 months viral load 1600 c/ml	33 weeks premature, multiple neonatal complications Viral load at birth 3,000 million c/ml; VL<20 at 1 month and remains undetectable

The fourth case described above illustrates what can be achieved in difficult circumstances. In this instance, the child was premature and initially unwell, requiring many weeks of hospital admission. This provided the opportunity for relationships to be established between social workers and the family, and ultimately resulting in a successful outcome. In contrast, what is more typically observed is the lost opportunity to achieve rapid suppression of viraemia in newborns diagnosed in the first days of life. Indeed, in case 3, the infant had undetectable plasma viremia initially, having received trans-placental ART. However, despite the parents – unusually - being married, educated and employed, the mother had become disillusioned with ART, having herself been poorly counselled during pregnancy.

In summary, in the era of effective PMTCT, the same psychosocio-economic factors that predispose to mother-to-child transmission also substantially increase the likelihood of ART failure in infected infants. For this reason, maximum efforts now need to to be invested in addressing the fundamental challenges faced by these high-risk mothers, since only then will the benefits of early infant diagnosis be fully realised.