Current HIV Research - Volume 11, Issue 2, 2013

The global epidemiology of HIV/AIDS is rapidly evolving in low and middle income countries. Women and adolescent females in Sub-Saharan Africa are at risk of HIV acquisition due to a myriad of complex biological, behavioral and structural factors. Primary HIV infection among women primarily drives the pediatric HIV epidemic. Postnatal transmission of HIV during breastfeeding is a major concern in LMIC, particularly in Sub-Saharan Africa where breastfeeding remains the only feasible, safe and culturally acceptable infant feeding choice. Given the remarkable discoveries in biomedical interventions to prevent sexual transmission of HIV and MTCT during breastfeeding, there is now a unique opportunity to rapidly implement combination HIV prevention packages, provide quality prevention of mother-to-child HIV transmission services, and improve maternal and infant survival. Although rapid scale-up of PMTCT interventions has occurred in Sub-Saharan Africa in the past five years, significant challenges remain towards reaching the ambitious goal of virtual elimination of new HIV infections among children on a global scale by 2015 and keeping their mothers alive. Rapid translation of scientific discoveries into policy and practice in conjunction with strong commitment from national leadership and global partners is crucial to end the pediatric AIDS and achieve a HIV-free generation.

Mother-to-child transmission (MTCT) of HIV continues to fuel the worldwide pediatric HIV epidemic. Without any intervention to prevent transmission, the rate of MTCT of HIV is estimated at 12-40%. The prevalence of pediatric HIV infection in a given community is the sensor for both the magnitude and the trajectory of the HIV epidemic in that community. A myriad of viral and host risk factors act in tandem to cause MTCT of HIV. In this review, the mechanisms, timing of transmission, and risks factors (i.e. viral and host) associated with MTCT of HIV are discussed. Although significant declines in MTCT have been achieved in both resource-rich and resource-limited countries over time, there are still challenges and threats that have the potential to reverse the gains made so far. Understanding the mechanisms, timing, and viral and host factors associated with MTCT of HIV will help to identify appropriate interventions and suitable antiretroviral chemoprophylaxis regimens to reduce or eliminate MTCT.

In low and middle-income countries (LMIC), transmission of HIV during breastfeeding represents a major public health challenge. Several viral, maternal clinical, immunological and genetic factors, as well as maternal-infant host factors and type of infant feeding may influence the risk of breastfeeding transmission of HIV. The mechanisms of breast milk HIV transmission are poorly understood. For mothers who are healthy and do not need combination antiretroviral therapy for their own health, randomized controlled trials have proven that administration of extended maternal triple-drug antiretroviral (ARV) prophylaxis or extended infant ARV prophylaxis can significantly reduce the risk of HIV transmission during breastfeeding. Based on this evidence, the World Health Organization (WHO) published new guidance in 2010 on the use of ARVs for treating pregnant women, and preventing mother-to-child HIV transmission (PMTCT). Although, remarkable advances have occurred in prevention of postnatal transmission during breastfeeding using antiretroviral strategies, a number of challenges remain. Future research must focus on field studies to evaluate programmatic implementation of new WHO PMTCT regimens, monitor long-term safety of ART exposure during pregnancy and lactation, and study emergence of ARV resistance (in mothers and infected infants despite prophylaxis).

The purpose of this article is to review prominent studies on HIV drug-resistance in mothers and their infants after the use of antiretroviral drugs to prevent mother-to-child-transmission in resource-limited communities. The effects of drug-resistance on subsequent combination antiretroviral therapy are discussed, as are the probable mechanisms of acquisition and decay or persistence of drug-resistant mutants. Differences in the rates of HIV drug-resistance from interventions used to prevent mother-to-child-transmission in North America and Europe are contrasted to the simplified regimens used in resource-limited settings. Unresolved issues related to HIV drug-resistance are reviewed, including: whether maternal zidovudine monotherapy selects significant resistance; the clinical relevance of HIV drug-resistant variants selected by single-dose nevirapine that persist as minority viral variants and can affect the outcome of nonnucleoside reverse transcriptase inhibitor-based therapy; and the use of maternal combination antiretroviral therapy during breastfeeding. Finally, the current and upcoming strategies to reduce HIV drug-resistance related to use of antiretrovirals to prevent mother-to-child-transmission are discussed and contrasted with the challenges of financing and administering antiretrovirals to prevent mother-to-child-transmission in resource-limited communities.

Although pharmacological interventions have been successful in reducing prevention of maternal to child transmission (PMTCT) of HIV, there is concern that complete elimination through this mode of transmission will require other measures. Immunotherapies in infants or pregnant mothers may be able to eradicate this form of transmission. A recent vaccine trial in adults showed encouraging results, but as in most HIV safety and efficacy vaccine trials, the question of MTCT was not addressed. Concentrating transmission studies and vaccine studies in the setting of MTCT offers several advantages. MTCT has a generally reproducible known transmission rate and has been successfully used to assess pharmacological interventions on decreasing transmission. Even in resource poor settings, the infrastructure for neonatal vaccination is already in place. Although rare, both passive and active vaccination trials have been successfully completed in pediatric populations. Unfortunately, little success in affecting MTCT has been shown. Largely, a correlate of protection in any type of transmission, including MTCT, is unknown. Data supports a role for antibodies in effecting strain and transmission during MTCT. The role of antibodies in MTCT is reviewed with a focus on recent passive immunization and considerations for future studies.

Over the past 10 years substantial progress has been made in the implementation of prevention of mother-tochild transmission of HIV (PMTCT) interventions in Sub-Saharan Africa (SSA). In spite of this, new pediatric infections remain unacceptably high, contributing the majority (>90%) of the estimated 390,000 infections globally in 2010; and yet prolonged breastfeeding remains the norm and crucial to overall infant survival. However, there is reason for optimism given the 2010 World Health Organization PMTCT recommendations: to start HIV infected pregnant women with CD4 cell counts less than 350 cells/mm3 on lifelong antiretroviral therapy (ART); and for mothers not eligible for ART to provide efficacious maternal and/or infant PMTCT antiretroviral (ARV) regimens to be taken during pregnancy, labor/delivery and through breastfeeding. Current attention is on whether to extend maternal ARVs for life once triple ARV PMTCT regimens are started. To dramatically reduce new pediatric infections, individual countries need to politically commit to rapid scale-up of a multi-pronged PMTCT effort: including primary prevention to reduce HIV incidence among women of reproductive age; increased access to family planning services; HIV screening of all pregnant and breastfeeding women followed by ART or ARVs for PMTCT; and comprehensive care for HIV affected families. Efforts to achieve population-level success in SSA need to critically address operational issues and challenges to implementation (health system) and utilization (social, economic and cultural barriers), at the country, health centre and client level that have led to the relatively slow progress in the scale-up of PMTCT strategies.

Objective: Review key topics and recent literature regarding reproductive health and family planning needs for HIV-infected women in Sub-Saharan Africa. Methods: Electronic searches performed in PubMed, JSTOR, and Web of Science; identified articles reviewed for inclusion. Findings: Most HIV-infected women in Sub-Saharan Africa bear children, and access to antiretroviral therapy may increase childbearing desires and/or fertility, resulting in greater need for contraception. Most contraceptive options can be safely and effectively used by HIV-infected women. Unmet need for contraception is high in this population, with 66- 92% of women reporting not wanting another child (now or ever), but only 20-43% using contraception. During pregnancy and delivery, HIV-infected women need access to prevention of mother-to-child transmission (PMTCT) services, a skilled birth attendant, and quality post-partum care to prevent HIV infection in the infant and maximize maternal health. Providers may lack resources as well as appropriate training and support to provide such services to women with HIV. Innovations in biomedical and behavioral interventions may improve reproductive healthcare for HIVinfected women, but in Sub-Saharan Africa, models of integrating HIV and PMTCT services with family planning and reproductive health services will be important to improve reproductive outcomes. Conclusions: HIV-infected women in Sub-Saharan Africa have myriad needs related to reproductive health, including access to high-quality family planning information and options, high-quality pregnancy care, and trained providers. Integrated services that help prevent unintended pregnancy and optimize maternal and infant health before, during and after pregnancy will both maximize limited resources as well as provide improved reproductive outcomes.

Purpose: The purpose of the study was to describe male involvement in programmes for preventing mother-tochild transmission (PMTCT) in Sub-Saharan Africa. The study questions guiding this review were: how are male partners involved in PMTCT programmes in Sub-Saharan Africa and what are the strategies for improvement of male involvement? Methods: An integrative review was conducted based on the data retrieved from the PubMed MEDLINE database. In all, 18 articles were included in this review. Qualitative content analysis was used as a method of data synthesis. Findings: Based on the findings of this review, some studies suggested that men had positive attitudes towards PMTCT programmes. However, also barriers to male involvement were identified. These barriers included negative attitude, lack of resources, fear of human immunodeficiency virus (HIV) test result, marital difficulties, problems with health care services and cultural barriers. Accepting HIV testing was associated with factors related to both wife and husband. Strategies for improving male involvement included ones that focus on men’s and their wives’ resources (sensitizing men about antenatal care (ANC) and PMTCT, focusing on the conjugal context and couples counselling), the development of health care services (tailoring the services to male needs, taking care of health care staff’s resources, developing health care strategies) and the community (educating the community, testing, safer infant feeding). Implications: We should highlight the male participation in PMTCT programmes. However, more research is needed in order to evaluate their impact on PMTCT, as well as on broader family health outcomes.