Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts.

PEPFAR's response to the convergence of the HIV and COVID-19 pandemics in Sub-Saharan Africa.

INTRODUCTION: The COVID-19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID-19 preparedness and response plans were rapidly instituted across sub-Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID-19 pandemic would have in under-resourced settings with high burdens of PLHIV. The potential negative impact of COVID-19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID-19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID-19-related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID-19. This commentary reviews PEPFAR's COVID-19 technical guidance and provides country-specific examples of programme adaptions in sub-Saharan Africa. DISCUSSION: The COVID-19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over-burdened health systems. Although there is currently limited understanding of how COVID-19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID-19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in-person home and facility visits and other direct contact when COVID-19 control measures are in effect. PEPFAR-supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID-19 in sub-Saharan Africa. CONCLUSIONS: As community transmission of COVID-19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data-driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID-19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.

Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding women and their infants: the promise of innovative service delivery models.

INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. DISCUSSION: Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. CONCLUSIONS: Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake of services for families. However, with decreasing funding, stable HIV incidence, and aspirations for sustainability, it is critical to consider efficient, customized and cost-effective models of care for these populations as we aspire to eliminate mother-to-child transmission of HIV.

Interventions to significantly improve service uptake and retention of HIV-positive pregnant women and HIV-exposed infants along the prevention of mother-to-child transmission continuum of care: systematic review.

OBJECTIVES: Despite the success of Prevention of Mother-to-Child Transmission of HIV (PMTCT) programmes, low uptake of services and poor retention pose a formidable challenge to achieving the elimination of vertical HIV transmission in low- and middle-income countries. This systematic review summarises interventions that demonstrate statistically significant improvements in service uptake and retention of HIV-positive pregnant and breastfeeding women and their infants along the PMTCT cascade. METHODS: Databases were systematically searched for peer-reviewed studies. Outcomes of interest included uptake of services, such as antiretroviral therapy (ART) such as initiation, early infant diagnostic testing, and retention of HIV-positive pregnant and breastfeeding women and their infants. Interventions that led to statistically significant outcomes were included and mapped to the PMTCT cascade. An eight-item assessment tool assessed study rigour. PROSPERO ID: CRD42017063816. RESULTS: Of 686 citations reviewed, 11 articles met inclusion criteria. Ten studies detailed maternal outcomes and seven studies detailed infant outcomes in PMTCT programmes. Interventions to increase access to antenatal care (ANC) and ART services (n = 4) and those using lay cadres (n = 3) were most common. Other interventions included quality improvement (n = 2), mHealth (n = 1), and counselling (n = 1). One study described interventions in an Option B+ programme. Limitations included lack of HIV testing and counselling and viral load monitoring outcomes, small sample size, geographical location, and non-randomized assignment and selection of participants. CONCLUSIONS: Interventions including ANC/ART integration, family-centred approaches, and the use of lay healthcare providers are demonstrably effective in increasing service uptake and retention of HIV-positive mothers and their infants in PMTCT programmes. Future studies should include control groups and assess whether interventions developed in the context of earlier 'Options' are effective in improving outcomes in Option B+ programmes.

Adolescents, young people, and the 90-90-90 goals: a call to improve HIV testing and linkage to treatment.

: The current low rates of HIV diagnosis and treatment initiation among adolescents and young people ages 15-24 continues to present a significant challenge to the epidemic control of HIV. With a 'business as usual' approach to HIV testing and linkage to treatment, new infections among adolescents and youth will likely increase, with the burden compounded by the increasing number of youth in Africa, expected to reach 293 million by 2025. Recent studies reveal significant gaps in the HIV clinical cascade among young people as the global community pursues the Joint United Nations Programme on HIV and AIDS 90-90-90 targets. This AIDS supplement was commissioned with the goal of informing program planners, researchers, policymakers, and funding agencies about the development and design of effective adolescent and youth programs, policies, and strategies for improving the first two 90s among adolescents and youth: HIV testing and diagnosis and linkage to care and treatment. Emerging evidence should inform efforts to better target the youth and adolescents who are most at risk, aiming for early diagnosis and treatment initiation for those who are HIV positive, while also ensuring appropriate primary prevention so that those identified as HIV negative remain so.

Talking to children about their HIV status: a review of available resources, tools, and models for improving and promoting pediatric disclosure.

As children living with HIV (CLHIV) grow into adolescence and adulthood, caregivers and healthcare providers are faced with the sensitive challenge of when to disclose to a CLHIV his or her HIV status. Despite WHO recommendations for CLHIV to know their status, in countries most affected by HIV, effective resources are often limited, and national guidance on disclosure is often lacking. To address the need for effective resources, gray and scientific literature was searched to identify existing tools and resources that can aid in the disclosure process. From peer-reviewed literature, seven disclosure models from six different countries were identified. From the gray literature, 23 resources were identified including children's books (15), job aides to assist healthcare providers (5), and videos (3). While these existing resources can be tailored to reflect local norms and used to aid in the disclosure process, careful consideration must be taken in order to avoid damaging disclosure practices.

Challenges and Opportunities in the Development of HIV Medications in Pediatric Patients.

Successful management of pediatric HIV disease requires high therapeutic efficacy and adherence, which can be achieved by providing affordable, easy to store, and palatable antiretrovirals. Current challenges in pediatric antiretroviral drug development include poor palatability, large pill size, limited oral liquid formulations, and few incentives for development by drug manufacturers as the number of children with HIV continues to decline due to successful worldwide preventive interventions and improved access to antiretrovirals. This article summarizes the various challenges and opportunities with current pediatric antiretrovirals, recent and ongoing trials, new formulations, and suggestions that may expedite and provide incentives for the development of suitable pediatric formulations.

Retention of mothers and infants in the prevention of mother-to-child transmission of HIV programme is associated with individual and facility-level factors in Rwanda.

OBJECTIVES: Investigate levels of retention at specified time periods along the prevention of mother-to-child transmission (PMTCT) cascade among mother-infant pairs as well as individual- and facility-level factors associated with retention. METHODS: A retrospective cohort of HIV-positive pregnant women and their infants attending five health centres from November 2010 to February 2012 in the Option B programme in Rwanda was established. Data were collected from several health registers and patient follow-up files. Additionally, informant interviews were conducted to ascertain health facility characteristics. Generalized estimating equation methods and modelling were utilized to estimate the number of mothers attending each antenatal care visit and assess factors associated with retention. RESULTS: Data from 457 pregnant women and 462 infants were collected at five different health centres (three urban and two rural facilities). Retention at 30 days after registration and retention at 6 weeks, 3, 6, 9 and 12 months post-delivery were analyzed. Based on an analytical sample of 348, we found that 58% of women and 81% of infants were retained in care within the same health facility at 12 months post-delivery, respectively. However, for mother-infant paired mothers, retention at 12 months was 74% and 79% for their infants. Loss to facility occurred early, with 26% to 33% being lost within 30 days post-registration. In a multivariable model retention was associated with being married, adjusted relative risk (ARR): 1.26, (95% confidence intervals: 1.11, 1.43); antiretroviral therapy eligible, ARR: 1.39, (1.12, 1.73) and CD4 count per 50 mm(3), ARR: 1.02, (1.01, 1.03). CONCLUSIONS: These findings demonstrate varying retention levels among mother-infant pairs along the PMTCT cascade in addition to potential determinants of retention to such programmes. Unmarried, apparently healthy, HIV-positive pregnant women need additional support for programme retention. With the significantly increased workload resulting from lifelong antiretroviral treatment for all HIV-positive pregnant women, strategies need to be developed to identify, provide support and trace these women at risk of loss to follow-up. This study provides further evidence for the need for such a targeted supportive approach.

The effect of probiotics on CD4 counts among people living with HIV: a systematic review.

Probiotics are defined by the WHO as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. Ongoing research has shown probiotics provide benefits to humans, including protection and restoration of the gastrointestinal and other mucosal tracts. As human immunodeficiency virus (HIV) activates gut-associated lymphoid tissue (GALT), several studies have investigated the effect of probiotics on CD4 cell count and related outcomes among those living with HIV. These studies are summarised here. Manuscripts were identified using the search terms 'probiotics', 'synbiotics', 'HIV', and 'CD4', and were reviewed for relevance and inclusion of CD4 count as an immunologic endpoint. Bibliographies of relevant manuscripts were also reviewed for additional studies matching inclusion and exclusion criteria. The search yielded 91 results; 13 included relevant outcomes. Seven of these studies produced beneficial CD4 outcomes, while the remaining 6 reported on insignificant beneficial or negative CD4 outcomes. The studies summarised here collectively suggest that daily consumption of probiotics over a prolonged period of time may improve CD4 count in people living with HIV.

A systematic review of the effect of HIV infection and antiretroviral therapy on the risk of pre-eclampsia.

BACKGROUND: The associations between HIV infection, antiretroviral therapy (ART), and pre-eclampsia are unclear. OBJECTIVES: To summarize research and clarify the implications of HIV and ART on pre-eclampsia risk. SEARCH STRATEGY: MedLine, PubMed, Web of Science, and the Cochrane Library were searched for studies published between 2003 and July 2014, using relevant keywords. SELECTION CRITERIA: Full-text review was dependent on the inclusion of pre-eclampsia as an outcome and original data. DATA COLLECTION AND ANALYSIS: Data for population, confounders, limitations, and measures of association were qualitatively assessed. MAIN RESULTS: Among 550 records identified, 70 were screened, and 13 were included. Five of the nine studies comparing pre-eclampsia risk between women with and without HIV infection found no significant difference; only one found that women living with HIV were more likely to experience pre-eclampsia. Two studies found that women living with HIV who were receiving ART at conception were more likely to experience pre-eclampsia than were those not receiving ART at conception. Two studies reported that pre-eclampsia rates did not differ by ART regimen. CONCLUSIONS: There is insufficient evidence to conclude that women living with HIV and receiving ART have a higher risk of pre-eclampsia than do women without HIV infection; further research is needed to assess the association between ART and pre-eclampsia.

Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe.

OBJECTIVE: To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country. METHODS: A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10-19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record. RESULTS: Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10 y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates. CONCLUSIONS: During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.

Disclosure of HIV serostatus among pregnant and postpartum women in sub-Saharan Africa: a systematic review.

Disclosure of one's HIV status can help to improve uptake and retention in prevention of mother-to-child transmission of HIV services; yet, it remains a challenge for many women. This systematic review evaluates disclosure rates among pregnant and postpartum women in sub-Saharan Africa, timing of disclosure, and factors affecting decisions to disclose. PubMed and EMBASE databases were searched to identify relevant studies published between January 2000 and April 2014. Rates of HIV serostatus disclosure to any person ranged from 5.0% to 96.7% (pooled estimate: 67.0%, 95% CI: 55.7%-78.3%). Women who chose to disclose their status did so more often to their partners (pooled estimate: 63.9%; 95% CI: 56.7%-71.1%) than to family members (pooled estimate: 40.1; 95% CI: 26.2%-54.0%), friends (pooled estimate: 6.4%; 95% CI: 3.0%-9.8%), or religious leaders (pooled estimate: 7.1%; 95% CI: 4.3%-9.8%). Most women disclosed prior to delivery. Decisions to disclose were associated with factors related to the woman herself (younger age, first pregnancies, knowing someone with HIV, lower levels of internalized stigma, and lower levels of avoidant coping), the partner (prior history of HIV testing and higher levels of educational attainment), their partnership (no history of domestic violence and financial independence), and the household (higher quality of housing and residing without co-spouses or extended family members). Interventions to encourage and support women in safely disclosing their status are needed.

Diagnosis of paediatric tuberculosis using sputum induction in Botswana: programme description and findings.

SETTING: Four public hospitals in Botswana, a high tuberculosis (TB) burden setting. OBJECTIVES: To assess the feasibility and utility of sputum induction in the diagnosis of paediatric TB. DESIGN: From 2008 to 2010, children aged ≤18 years referred for suspected pulmonary TB underwent sputum induction. Confirmed TB was defined as the presence of at least one of the signs and symptoms suggestive of TB and positive Mycobacterium tuberculosis culture. Information on TB-associated symptoms (cough, fatigue, night sweats, low appetite, chest pain, weight loss, haemoptysis and contact with a TB case) was collected for three risk groups: human immunodeficiency virus (HIV) positive children, HIV-negative children aged <3 years and HIV-negative children aged ≥3 years. RESULTS: The median age of the 1394 subjects who underwent sputum induction was 3.8 years (IQR 1.3-8.4); 373 (27%) were HIV-positive, 419 (30%) were HIV-negative and 602 (43%) had unknown HIV status. TB was confirmed in 84 (6.0%); cases were more likely to have weight loss, chest pain or TB household contacts. There were no serious complications attributable to sputum induction during and after the procedure; only 0.8% (9/1174) of patients reported minor complications. CONCLUSIONS: In Botswana, paediatric sputum induction was feasible, safe and assisted bacteriological confirmation in a subgroup of children treated for TB.

Does a significant reduction in malaria risk make lopinavir/ritonavir-based ART cost-effective for children with HIV in co-endemic, low-resource settings?

BACKGROUND: HIV infection and malaria co-infection is not uncommon among children in co-endemic regions, and evidence suggests that HIV is a risk factor for severe malaria among children. HIV protease inhibitors (PIs) are highly effective in pediatric HIV treatment regimens, however, their effectiveness against malaria has been mixed, with some PIs demonstrating in vitro activity against Plasmodium falciparum. Recent findings suggest lopinavir/ritonavir (LPV/r)-based treatment regimens reduce the incidence of malaria infection by over 40% in pediatric HIV patients compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: We assessed whether a significant reduction in malaria risk makes LPV/r-based ART regimens cost-effective compared to NNRTI-based regimens in co-endemic, low-resource settings. We modeled the difference in unit cost per disability adjusted life year (DALY) gained among two theoretical groups of HIV+ children under 5 years old receiving ART in a resource-limited setting co-endemic for malaria. The first group received standard NNRTI-based antiretrovirals, the second group received a standard regimen containing LPV/r. We used recent cohort data for the incidence reduction for malaria. Drug costs were taken from the 2011 Clinton Health Access Initiative Antiretroviral (ARV) ceiling price list. DALYs for HIV and malaria were derived from WHO estimates. RESULTS: Our model suggests a unit cost of US$147 per DALY gained for the LPV/r-based group compared to US$37 per DALY gained for the NNRTI-based group. CONCLUSION: In HIV and malaria co-endemic settings, considerations of PI cost effectiveness incorporating known reductions in malaria mortality suggest a nominal increase in DALYs gained for PIs over NNRTI-based regimens for HIV positive children under five on ART. Our analysis was based on several assumptions due to lack of sound data on malaria and HIV DALY attribution among pediatric populations. Further study in this area is required.

Beyond prevention of mother-to-child transmission: keeping HIV-exposed and HIV-positive children healthy and alive.

In 2011, Joint United Nations Programme on HIV/AIDS announced a plan to eliminate new HIV infections among children by 2015. This increased focus on the elimination of maternal to child transmission (MTCT) is most welcome but is insufficient, as access to prevention of MTCT (PMTCT) programming is neither uniform nor universal. A new and more expansive agenda must be articulated to ensure that those infants and children who will never feel the impact of the current elimination agenda are reached and linked to appropriate care and treatment. This agenda must addresses challenges around both reducing vertical transmission through PMTCT and ensuring access to appropriate HIV testing, care, and treatment for all affected children who were never able to access PMTCT programming. Option B+, or universal test and treat for HIV-infected pregnant women is an excellent start, but it may be time to rethink our current approaches to delivering PMTCT services. New strategies will reduce vertical transmission to less than 1% for those mother-infant pairs who can access them allowing for the contemplation of not just PMTCT, but actual elimination of MTCT. But expanded thinking is needed to ensure elimination of pediatric HIV.