These vaccines are now entering expanded human clinical trials. Other approaches to develop an effective HIV vaccine are also underway and include novel vector strategies as well as structural biology-based approaches. A recent study demonstrated that a live replicating cytomegalovirus CMV vaccine encoding several simian immunodeficiency virus SIV proteins, administered prior to SIV challenge, can lead to complete viral suppression and elimination of detectable SIV infection in about half of the rhesus macaques studied, implying that some lentiviral infections may be susceptible to clearance via effector memory T cell-mediated mechanisms [ 30 ].
This study provides new insights into the role of effector memory CD8 T-cells in control and elimination of SIV infection and, more generally, how to elicit long-term tissue resident immune responses at the mucosal sites where HIV acquisition occurs. Whether similar immune responses are translatable to humans and can lead to continued clinical development of this live attenuated vaccine approach remains to be determined. In addition, further evaluation of the immune responses of the macaques that did not clear their SIV infection is imperative to further the understanding of the correlates of sustained SIV infection post CMV vaccination.
A worldwide effort to isolate broadly neutralizing antibodies to HIV and to understand the structural basis for their neutralization as well as the immunological basis for their development [ 31 — 33 ] has brought insights into the design of new candidate vaccines as well as antibody-targeted approaches. A major impediment to advancing HIV vaccine development has been the painstakingly slow pace of conducting vaccine efficacy trials, largely due to the difficulty in producing good manufacturing practice GMP quantities of novel HIV envelope proteins or recombinant vectors with novel inserts.
Engaging industry to actively embrace such high-risk ventures has been difficult, but it is a necessary hurdle for the HIV vaccine field to solve. Developing such resolve and expertise is difficult in a field in which scientific pluralism is valued and required.
The Quest for an HIV Vaccine
Despite the challenge of developing an HIV vaccine, mathematical modelling has verified the profound impact a vaccine with variable coverage—even low-efficacy vaccines in combination with other interventions—would have at a population level [ 34 , 35 ]. Numerous studies over the past 15 years have demonstrated the ability of HIV-1 neutralizing antibodies to prevent the acquisition of simian—human immunodeficiency virus SHIV infection in NHPs [ 36 — 39 ].
Technologies to manufacture these antibodies in sufficient quantities are now available, enabling test-of-concept trials exploring whether the infusion of one or more antibodies could persistently reduce viremia in HIV-infected persons. Perhaps more importantly, human clinical trials are being convened, exploring whether infusion of monoclonal antibodies could prevent HIV acquisition.
If clinical trial proof was obtained that neutralizing antibodies could markedly reduce HIV acquisition, it would be a conceptual breakthrough in the HIV prevention landscape and would validate the need to develop a neutralizing antibody vaccine. Applying the knowledge gleaned from cancer, autoimmune, and inflammatory diseases to increase the potency of antibodies by improving effector function of antibodies, such as enhancing ADCC and increasing serum half-life of IgG through Fc engineering [ 41 — 43 ], may improve the utility of this intervention for HIV treatment and prevention.
In sub-Saharan Africa, more than two-thirds of infections occur among women aged between 15 and 24 years. Young women typically acquire HIV infection 5—7 years earlier than their male counterparts [ 44 , 45 ]. HIV infections among women, especially young women, can be as much as 8-fold higher than in men of the same age [ 46 ] and is an important driver of the epidemic in Africa [ 47 ].
Candidate microbicides are being developed in an array of formulations, including gels, vaginal rings, rapidly dissolving vaginal tablets, films, and gel-filled compartments in diaphragms. Adherence markedly affects the effectiveness of all PrEP regimens, and suboptimal adherence remains a large challenge for microbicide development [ 48 , 49 ], which was seen again in FACTS , a recent phase III confirmation study of coitally applied tenofovir gel [ 50 ].
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To overcome these problems, long-acting, slow-release products are under development, including dapivirine or tenofovir in a vaginal ring [ 51 , 52 ]. In the future, multipurpose prevention technologies e. Rectal microbicide formulations for men and women at risk of HIV acquisition through anal intercourse are also under investigation [ 54 ]. The continued development of safer, better priced, and more convenient ARVs has resulted in the ongoing improvement of health for HIV-infected persons on both an individual and population basis.
In the developed world, over a million deaths were averted by ARV treatments in the last decade. Still, there were 1. The most formidable barrier to the ubiquitous use of treatment is access. Communities and health systems experience enormous infrastructural and human resource shortcomings to early testing and treatment, drug supply, and retention in care.
However, important innovations in drugs, treatment strategies, and monitoring are emerging that can solidify the expansion and resilience of treatment programs. A drug development priority in a population-based scale-up of ART is a first-line single tablet that requires minimal laboratory monitoring and possesses minimal side effects with low rates of HIV resistance. The latest US guidelines adopt the use of an integrase inhibitor with two nucleoside reverse transcriptase inhibitors as first-line therapy.
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The latter coformulation showed virologic responses similar to its TDF equivalent but had better renal and bone profiles. In the developing world, future scale-up could be eased by prioritizing in-country licensure and cost reduction of such new drugs. Even with maximum improvements on a single daily pill, ultimate scale-up must consider critical issues affecting retention in care, such as the lack of money for transport [ 57 ] and the challenges of getting time off work for patients to attend a clinic and collect medication.
Drug delivery approaches that would guarantee longer-term adherence, such as drug implants, are being studied. Furthermore, the landscape of health staffing may need to transform, as the necessity of increasing personnel to handle increased patient volumes may require shifting tasks even further from nurses to trained counsellors to assist with monitoring and retention in care Table 1.
A multicountry pre-exposure prophylaxis trial in infants found similar infection rates of 1. These findings must be rapidly operationalised to curtail the quarter of a million new childhood infections that occur annually. Here, again, the vexing issue is access, highlighting the kind of health infrastructure investments required to identify and treat all pregnant women with HIV Table 2.
South Africa is the first country to report on population-level effectiveness of a national PMTCT programme [ 61 ] and has demonstrated a consistent trend toward lowering transmission among infants, with rates of 2. The effectiveness of PMTCT interventions in the field are influenced by access to prenatal care, retention in care, ARV adherence, adequate education, and follow-up of the mother and infant post-delivery Table 2.
To achieve adequate viral load suppression at the time of delivery, ARVs should be initiated early in pregnancy [ 12 ]. Incident cases of HIV occurring during pregnancy and lactation increase the risk of mother-to-child transmission. Implementing repeat HIV testing in late pregnancy and during breastfeeding will be a further critical step required on the road to elimination [ 68 ]. Hopefully, as more women are initiated on lifelong treatment, the continuum of care will improve so that prevention benefits are realised.
One report from Malawi, however, acts as a cautionary tale: one in ten women were lost to follow-up six months after ART initiation Table 3 [ 69 ]. Furthermore, solving the issues of health care stigmatization, access, status disclosure, and spousal involvement will also be needed to improve treatment initiation, adherence, and retention in care [ 70 ]. Increased morbidity and mortality amongst HIV-exposed uninfected children has been described, including birth defects [ 71 ], small for gestational age SGA infants [ 72 ], growth [ 73 ] and neurodevelopmental delay [ 74 ], and reduced immunity to vaccine-preventable diseases [ 75 , 76 ].
There is an urgent need to better understand the health consequences of exposure to HIV and antiretroviral drugs on HIV-uninfected children and to improve monitoring and management of this growing subpopulation of children. HIV can reactivate from these cells, however, and their presence constitutes a major barrier to eradicating infection [ 78 , 79 ].
Advances in understanding the basic biology of HIV have provided a framework to conceptualise novel approaches to curing the disease. The benefits of such an approach on interrupting the spread of HIV are enormous and warrant a full-scale effort by the international scientific community. HIV brought an unprecedented shift in the global landscape of public health: it slashed life expectancy and wiped out a generation of economically active adults in their prime in sub-Saharan Africa; it reversed gains in under-five mortality and created a cohort of AIDS orphans; and it exposed the underbelly of poor health systems.
Preventing unintended pregnancies in women living with HIV in resource-poor settings
It has also revealed the interrelatedness between social behaviour, stigmatization, cultural mores, religious beliefs, and human health. HIV has challenged all societies in our attempts to deal with its economic, societal, and medical aspects. Even with all the biomedical and behavioural tools available today, HIV continues to be a formidable pathogen, altering the health economics and public health strategies of most countries worldwide.
Of the 35 million HIV-infected individuals worldwide in , more than half did not know their HIV status, and over a third were not receiving ARVs [ 1 ] despite the availability of affordable point-of-care diagnostics and treatments. However, it must also be recognised that true containment of the epidemic requires the development and widespread implementation of a scientific advance that has eluded us to date—a highly effective vaccine. In the s it was used as an instrument for screening, so that women at higher risk of complications could be identified.
Although antenatal care turned out to be a poor screening instrument, few people would deny that many pregnancy complications, concurrent illnesses and health problems can be dealt with in an antenatal care consultation that focuses on effective interventions. Antenatal care has come a long way, but can go much further.
Four directions are critical: to rationalize the rituals of care, to roll out antenatal care as a platform for a number of other key health programmes, to establish communication with women more effectively, and to avoid the overmedicalization that can do more harm than good. Most importantly, the unfinished agenda of reaching all women who are pregnant should be tackled.
All too often, antenatal care is still more a question of ritual than of effective interventions.
Many of the tests and procedures carried out during a traditional antenatal consultation have very little scientific merit Many ineffective interventions, such as routine weighing of the woman at each consultation to assess maternal well-being and fetal growth, could be dispensed with They take up valuable time which could be more usefully dedicated to counselling women on healthy lifestyles and health problems such as the detection and management of existing diseases. The potential for antenatal care to be much more far-reaching in this respect has not been fully exploited. WHO guidelines are readily available 42 to advise on care, prevention and treatment of diseases during pregnancy.
Moreover, pregnancy is a time when a dialogue about health and relevant social issues can be established between women and health services staff. Establishing communication with women and linking up the medical and social worlds will make care more human, and ultimately more responsive. A frequently forgotten issue is that of supply-driven overmedicalization of normal pregnancies, sometimes for reasons of financial gain.
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Overmedicalized care can needlessly damage the health of both mothers and babies and expose households to unnecessary expenditure. All too often, sophisticated investigations such as ultrasound scanning are performed without justification at every antenatal visit, while useful procedures such as blood pressure measurement are neglected and the establishment of birth plans and counselling on existing health problems are omitted. This has gone to extremes in some countries, where ultrasound is used to detect female fetuses for the purposes of sex-selective abortion.
In terms of coverage, there is some way to go to provide at least four care contacts during each pregnancy, starting early enough to ensure that effective interventions are used. Women need providers who are skilled enough to offer care that is linked into a health care system that has continuity with childbirth care. The barriers to extending coverage are twofold. First, in some areas no services are offered, implying the need for outreach or services that can be physically accessed. Second, services are often not responsive enough.
Complaints of unhelpful and rude health personnel, unexpected and unfair costs, unfriendly opening hours and the lack of involvement of male partners are not uncommon. Relatively straightforward changes to the arrangements of how antenatal care sessions are run for instance not limiting antenatal care to one session per week can sometimes make significant improvements to uptake. Adolescent girls are particularly vulnerable in this respect. Services that are responsive to them and young women will make a great contribution to the expansion of antenatal care.
The question should not be "why do women not accept the service that we offer? WHO systematic review of randomised controlled trials of routine antenatal care. Lancet, , — Antenatal care in developing countries. Promises, achievements, and missed opportunities. An analysis of trends, levels, and differentials — Geneva, World Health Organization, Effectiveness of antenatal care: a population based study. British Journal of Obstetrics and Gynaecology, , — Is routine antenatal care worth while? Measuring maternal mortality. In: Bere M, Ravindran T, eds. Safe motherhood initiatives: critical issues.
The postpartum period: the key to maternal mortality. International Journal of Gynecology and Obstetrics, , — Maternal mortality in Vietnam. Studies in Family Planning, , — Cairo, Ministry of Health and Population, Hospitalization for pregnancy complications, United States, and American Journal of Obstetrics and Gynecology, , — Tools for monitoring the effectiveness of district maternity referral systems. Health Policy and Planning, , — Maternal morbidity and mortality in two different populations of Senegal: a prospective study MOMA survey.
BJOG, , — Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Bleeding during the latter half of pregnancy. In: Chalmers I, Enkin M. Effective care in pregnancy and childbirth. Oxford, Oxford University Press, The burden of malaria in pregnancy in malaria-endemic areas. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy.
African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death. American Journal of Tropical Medicine and Hygiene, , — Predictors of mortality in Gambian children with severe malaria anaemia. Annals of Tropical Paediatrics, , — Severe anaemia in children living in a malaria endemic area of Kenya. Tropical Medicine and International Health, , — In-hospital morbidity and mortality due to malaria-associated severe anaemia in two areas of Malawi with different patterns of malaria infection.
Severe anaemia in Zambian children with Plasmodium falciparum malaria.
Effect of blood transfusion on survival among children in a Kenyan hospital. Indicators of life-threatening malaria in African children. New England Journal of Medicine, , — Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.
Insecticide-treated bednets and curtains for preventing malaria Cochrane Review. A Reference guide ISBN 92 4 6 that provides more technical and practical details than the counseling cards. Counsellors can use it as a handbook. An Orientation guide ISBN 92 4 4 that suggests ways for health care managers to train infant feeding counsellors on how to use these tools.
The new recommendations call for earlier initiation of antiretroviral therapy ART for adults and adolescents, the delivery of more patient-friendly antiretroviral drugs ARVs , and prolonged use of ARVs to reduce the risk of mother-to-child transmission of HIV. It reviews scientific evidence on the risk of HIV transmission through breastfeeding, the impact of different feeding options on child health outcomes, and conceivable strategies to reduce HIV transmission through breastfeeding with an emphasis on the developing world.
Facts for life - Breastfeeding - HIV - Safe Motherhood - Newborn Health The handbook, Facts for Life, provides vital messages and information for mothers, fathers, other family members and caregivers and communities to use in changing behaviours and practices that can save and protect the lives of children and help them grow and develop to their full potential.
Spotlight on PMTCT: Reducing Mother-to-Child Transmission of HIV among Women who Breastfeed The purpose of this issue of Spotlight is to provide decision makers, program managers, and health workers with guidance on how to support HIV-positive mothers who choose to breastfeed so that they can minimize the risk of transmission and protect their own health and the health of their infant.
For many HIV-positive mothers in resource-limited settings, breastfeeding is the only or the safest infant feeding strategy available. This guidance, based on the best information currently available, is for HIV-positive women who choose to transition from breastfeeding to replacement feeding at about 6 months. Modeling the effects of different infant feeding strategies on young child survival and mother-to-child transmission of HIV. Am J Pub Health ; This model is in Microsoft Excel. Author s : J.