Maria H. Kim

Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi.

Objective:To assess the continuity of care and outcome of pediatric HIV prevention, testing, and treatment services, focusing on early infant diagnosis with DNA polymerase chain reaction (PCR). Design:A retrospective observational cohort. Methods:Maternal HIV antibody, infant HIV DNA PCR test results, and outcome data from HIV-infected infants from the prevention of mother-to-child transmission, early infant diagnosis, and pediatric HIV treatment programs operating in Lilongwe, Malawi, between 2004 and 2008 were collected, merged, and analyzed. Results:Of the 14,669 pregnant women who tested HIV antibody positive, 7875 infants (53.7%) received HIV DNA PCR testing. One thousand eighty-four infants (13.8%) were HIV infected. Three hundred twenty (29.5%) children enrolled into pediatric HIV care, with 202 (63.1%) at the Baylor Center of Excellence. Among these, antiretroviral therapy was initiated on 110 infants (54.5%) whose median age was 9.1 months (interquartile range, 5.4-13.8) and a median of 2.5 months (interquartile range, 1.4-5.2) after HIV clinic registration. Sixty-nine HIV-infected infants (34.2%) died or were lost by December 2008. Initiation of antiretroviral therapy increased the likelihood of survival 7-fold (odds ratio, 7.1; 95% confidence interval, 3.68 to 13.70). Conclusions:Separate programs for maternal and infant HIV prevention and care services demonstrated high attrition rates of HIV-exposed and HIV-infected infants, elevated levels of mother-to-child transmission, late infant diagnosis, delayed pediatric antiretroviral therapy initiation, and high HIV-infected infant mortality. Antiretroviral therapy increased HIV-infected infant survival, emphasizing the urgent need for improved service coordination and strategies that increase access to infant HIV diagnosis, improve patient retention, and reduce antiretroviral therapy initiation delays.

Risks and benefits of lifelong antiretroviral treatment for pregnant and breastfeeding women: a review of the evidence for the Option B+ approach.

PURPOSE OF REVIEW Considerable debate has emerged on whether Option B+ (B+), initiation of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, is the best approach to achieving elimination of mother-to-child-transmission. However, direct evidence and experience with B+ is limited. We review the current evidence informing the proposed benefits and potential risks of the B+ approach, distinguishing individual health concerns for mother and child from program delivery and public health issues. RECENT FINDINGS For mothers and infants, B+ may offer significant benefits for transmission prevention and maternal health. However, several studies raise concerns about the safety of ART exposure to fetuses and infants, as well as adherence challenges for pregnant and breastfeeding mothers. For program delivery and public health, B+ presents distinct advantages in terms of transmission prevention to uninfected partners and increased simplicity potentially improving program feasibility, access, uptake, and retention in care. Despite being more costly in the short-term, B+ will likely be cost effective over time. SUMMARY This review provides a detailed analysis of risks and benefits of B+. As national programs adopt this approach, it will be critical to carefully assess both short-term and long-term maternal and infant outcomes.

The Tingathe programme: A pilot intervention using community health workers to create a continuum of care in the prevention of mother to child transmission of HIV (PMTCT) cascade of services in Malawi

Loss to follow‐up is a major challenge in the prevention of mother to child transmission of HIV (PMTCT) programme in Malawi with reported loss to follow‐up of greater than 70%. Tingathe‐PMTCT is a pilot intervention that utilizes dedicated community health workers (CHWs) to create a complete continuum of care within the PMTCT cascade, improving service utilization and retention of mothers and infants. We describe the impact of the intervention on longitudinal care starting with diagnosis of the mother at antenatal care (ANC) through final diagnosis of the infant.

Implementation and Operational Research: The Impact of Option B+ on the Antenatal PMTCT Cascade in Lilongwe, Malawi

Objective:In 2011, Malawi implemented Option B+ (B+), lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women. We aimed to describe changes in service uptake and outcomes along the antenatal prevention of mother-to-child transmission (PMTCT) cascade post-B+ implementation. Design:Pre/post study using routinely collected program data from 2 large Lilongwe-based health centers. Methods:We compared the testing of HIV-infected pregnant women at antenatal care, enrollment into PMTCT services, receipt of ART, and 6-month ART outcomes pre-B+ (October 2009–March 2011) and post-B+ (October 2011–March 2013). Results:A total of 13,926 (pre) and 14,532 (post) women presented to antenatal care. Post-B+, a smaller proportion were HIV-tested (99.3% vs. 87.7% post-B+; P < 0.0001). There were 1654 (pre) and 1535 (post) HIV-infected women identified, with a larger proportion already known to be HIV-infected (18.1% vs. 41.2% post-B+; P < 0.0001) and on ART post-B+ (18.7% vs. 30.2% post-B+; P < 0.0001). A significantly greater proportion enrolled into the PMTCT program (68.3% vs. 92.6% post-B+; P < 0.0001) and was retained through delivery post-B+ (51.1% vs. 65% post-B+; P < 0.0001). Among those not on ART at enrollment, there was no change in the proportion newly initiating ART/antiretrovirals (79% vs. 81.9% post-B+; P = 0.11), although median days to initiation of ART decreased [48 days (19, 130) vs. 0 days (0, 15.5) post-B+; P < 0.0001]. Among those newly initiating ART, a smaller proportion was alive on ART 6 months after initiation (89.3% vs. 78.8% post-B+; P = 0.0004). Conclusions:Although several improvements in PMTCT program performance were noted with implementation of B+, challenges remain at several critical steps along the cascade requiring innovative solutions to ensure an AIDS-free generation.

Mortality and Clinical Outcomes in HIV-Infected Children on Antiretroviral Therapy in Malawi, Lesotho, and Swaziland

OBJECTIVE: To determine mortality and immune status improvement in HIV-infected pediatric patients on antiretroviral treatment (ART) in Malawi, Lesotho, and Swaziland. METHODS: We conducted a retrospective cohort study of patients aged <12 years at ART initiation at 3 sites in sub-Saharan Africa between 2004 and 2009. Twelve-month and overall mortality were estimated, and factors associated with mortality and immune status improvement were evaluated. RESULTS: Included in the study were 2306 patients with an average follow-up time on ART of 2.3 years (interquartile range 1.5–3.1 years). One hundred four patients (4.5%) died, 9.0% were lost to follow-up, and 1.3% discontinued ART. Of the 104 deaths, 77.9% occurred in the first year of treatment with a 12-month mortality rate of 3.5%. The overall mortality rate was 2.25 deaths/100 person-years (95% confidence interval [CI] 1.84–2.71). Increased 12-month mortality was associated with younger age; <6 months (hazard ratio [HR] = 8.11, CI 4.51–14.58), 6 to <12 months (HR = 3.43, CI 1.96–6.02), and 12 to <36 months (HR = 1.92, CI 1.16–3.19), and World Health Organization stage IV (HR = 4.35, CI 2.19–8.67). Immune status improvement at 12 months was less likely in patients with advanced disease and age <12 months. CONCLUSIONS: Despite challenges associated with pediatric ART in developing countries, low mortality and good treatment outcomes can be achieved. However, outcomes are worse in younger patients and those with advanced disease at the time of ART initiation, highlighting the importance of early diagnosis and treatment.

Why Did I Stop? Barriers and Facilitators to Uptake and Adherence to ART in Option B+ HIV Care in Lilongwe, Malawi

Causes for loss-to-follow-up, including early refusals of and stopping antiretroviral therapy (ART), in Malawi’s Option B+ program are poorly understood. This study examines the main barriers and facilitators to uptake and adherence to ART under Option B+. In depth interviews were conducted with HIV-infected women who were pregnant or postpartum in Lilongwe, Malawi (N = 65). Study participants included women who refused ART initiation (N = 10), initiated ART and then stopped (N = 26), and those who initiated ART and remained on treatment (N = 29). The barriers to ART initiation were varied and included concerns about partner support, feeling healthy, and needing time to think. The main reasons for stopping ART included side effects and lack of partner support. A substantial number of women started ART after initially refusing or stopping ART. There were several facilitators for re-starting ART, including encouragement from community health workers, side effects subsiding, decline in health, change in partner, and fear of future sickness. Amongst those who remained on ART, desire to prevent transmission and improve health were the most influential facilitators. Reasons for refusing and stopping ART were varied. ART-related side effects and feeling healthy were common barriers to ART initiation and adherence. Providing consistent pre-ART counseling, early support for patients experiencing side effects, and targeted efforts to bring women who stop treatment back into care may improve long term health outcomes.

Beyond early infant diagnosis: case finding strategies for identification of HIV-infected infants and children.

There are 3.4 million children infected with HIV worldwide, with up to 2.6 million eligible for treatment under current guidelines. However, roughly 70% of infected children are not receiving live-saving HIV care and treatment. Strengthening case finding through improved diagnosis strategies, and actively linking identified HIV-infected children to care and treatment is essential to ensuring that these children benefit from the care and treatment available to them. Without attention or advocacy, the majority of these children will remain undiagnosed and die from complications of HIV. In this article, we summarize the challenges of identifying HIV-infected infants and children, review currently available evidence and guidance, describe promising new strategies for case finding, and make recommendations for future research and interventions to improve identification of HIV-infected infants and children.

Linkage, initiation and retention of children in the antiretroviral therapy cascade: an overview.

In 2012, there were an estimated 2 million children in need of antiretroviral therapy (ART) in the world, but ART is still reaching fewer than 3 in 10 children in need of treatment. [1, 7] As more HIV-infected children are identified early and universal treatment is initiated in children under 5 regardless of CD4, the success of pediatric HIV programs will depend on our ability to link children into care and treatment programs, and retain them in those services over time. In this review, we summarize key individual, institutional, and systems barriers to diagnosing children with HIV, linking them to care and treatment, and reducing loss to follow-up (LTFU). We also explore how linkage and retention can be optimally measured so as to maximize the impact of available pediatric HIV care and treatment services.

Prompt initiation of ART With therapeutic food is associated with improved outcomes in HIV-infected Malawian children with malnutrition.

Abstract:This retrospective observational study of 140 HIV-infected children with uncomplicated malnutrition in urban Malawi tested the hypothesis that initiation of antiretroviral therapy (ART) within 21 days of outpatient therapeutic feeding (prompt ART) improved clinical outcomes. Children receiving prompt ART were more likely to recover nutritionally (86% vs. 60%, P < 0.01) and had higher rates of weight gain (3.6 vs. 1.6 g/k/day; P = 0.02). Logistic regression modeling found prompt ART was associated with increased likelihood of nutritional recovery (odds ratio: 5.4, 95% confidence interval: 2.0 to 14.5). This suggests that prompt ART is associated with improved outcomes in HIV-infected Malawian children with uncomplicated malnutrition.

Low Rates of Mother-to-Child HIV Transmission in a Routine Programmatic Setting in Lilongwe, Malawi

Background The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi. Methods We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression. Results Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5–18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6–3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164). Conclusion Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery.