Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions

Abstract

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings.

Figure 1

Early infant diagnosis (EID) cascade: where could interventions be most effective and cost effective? The cascade of care required for optimally effective EID programs, with two primary goals: (1) correctly informing caregivers of infant infection status and (2) linking all HIV-infected infants to care and antiretroviral therapy (ART). BF = breastfeeding; CTX = cotrimoxazole; PMTCT = prevention of mother-to-child HIV transmission.

Figure 2

HIV RNA levels and anti-HIV antibody responses among HIV-exposed infants with and without HIV infection. Schematic depiction of the timing of positive HIV-1 antibody testing and RNA levels among HIV-exposed infants. The horizontal axis shows infant age in months. The left vertical axis shows mean HIV-1 RNA level on a logarithmic scale, and corresponds to the green lines on each graph. The right vertical axis shows the proportion of infants for whom an HIV antibody test would likely return positive, and corresponds to the red lines on each graph. The proportion of infants with a positive antibody test in all panels is approximate, based on a wide range of reported ages at which transmitted maternal HIV antibody fades from detection in the sera of uninfected infants [7,105]. Similarly, the mean RNA level is also approximate, based on several studies of infected infants with and without receipt of antiretroviral drugs for prevention of mother-to-child HIV transmission (PMTCT) [106-109]. (a) Results for an HIV-exposed infant who is born without HIV infection and remains uninfected throughout breastfeeding. In this case, HIV-RNA level remains zero, and maternal HIV antibody fades with time. (b) Results for infants infected before birth, either during the intrauterine period (IU; resulting in a high RNA level immediately after birth) or during the intrapartum period (IP; resulting in a 1-2 week delay before viremia is detectable). Maternal HIV antibody is present at birth; although maternal antibody fades with time, endogenous infant antibody production begins in response to infant infection. (c) Results for an HIV-exposed infant who is uninfected at birth, but becomes infected at approximately 6 months of age through breastfeeding. HIV RNA is undetectable while the infant is uninfected, but rises rapidly within the first few weeks after infection. Maternal antibody is present at birth and begins to fade with time, but infant antibody production begins after infant infection occurs.