HIV This Week

Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target. Walker LM, Phoga SK, Chan-Hui P-Y, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW, Protocol G Principal Investigators, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DL. Science. Published online September 3, 2009. Science DOI: 10.1126/science.1178746

Broadly neutralizing antibodies, which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, Walker and colleagues examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and selected donors for monoclonal antibody generation. They used a high-throughput neutralization screen of antibody-containing culture supernatants from approximately 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent monoclonal antibodies that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of broadly neutralizing antibody responses.

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Editors’ note: The two novel broadly neutralising antibodies described here are the first to be discovered in more than a decade and the first to be isolated from a donor in sub-Saharan Africa. They not only target multiple strains of HIV, i.e. they are broadly neutralising, but they are very potent, binding tightly to the virus and working at minute levels compared to previously discovered neutralising antibodies. As well, they reveal a new vulnerable easier-to-reach spot on the virus that no previously known antibody targets. The unusual features of these two monoclonal antibodies provide exciting new leads for the design of HIV vaccines that would stimulate the body to make potent antibodies that would be active against a broad range of strains of the virus when a person is exposed to the virus.

Household impacts of AIDS: using a life course analysis to identify effective, poverty-reducing interventions for prevention, tratment, and care. Loewenson R, Whiteside A, Hadingham J. Aids Care. 2009; 21:1032-1041

A life course approach was used to assess household level impacts and inform interventions around HIV risk and AIDS vulnerability across seven major age-related stages of life. The focus was sub-Saharan Africa. The authors provided a qualitative review of evidence from published literature, particularly multicountry reviews on impacts of AIDS, on determinants of risk and vulnerability, and reports of large surveys. Areas of potential stress from birth to old age in households affected by AIDS, and interventions for dealing with these specific stresses were identified. While specific interventions for HIV are important at different stages, achieving survival and development outcomes demands a wider set of health, social security, and development interventions. One way to determine the priorities amongst these actions is to give weighting to interventions that address factors that have latent impacts later in life, which interrupt accumulating risk, or that change pathways to reduce the risk of both immediate and later stress. This qualitative review suggests that interventions, important for life cycle transitions in generalized epidemics where HIV risk and AIDS vulnerability are high, lie within and outside the health sector, and suggests examples of such interventions.

Editors’ note: A life course concept views people as passing though various transitions and stages in life with events at one stage having effects at later stages. Points of stress in the life cycle that HIV can affect offer opportunities to influence pathways of accumulating vulnerability. These can range from the obvious example of preventing mother-to-child transmission by antiretroviral prophylaxis to broader interventions, such as promoting more open communication within families. HIV influences the number and quality of ‘buffers’ available to deal with stress, including the buffers of social support, financial resources, and good health. Household and individual resilience to shocks experienced in generalised epidemics can be supported through broader systems approaches within and beyond the health sector that help people to manage the interacting socioeconomic and health challenges of HIV. Examples include explicit interventions to strengthen social networks, increase spending on public services and community safety nets, introduce law reform and enforcement, invest in training and support for family carers, and increase access to education and employment opportunities.

Men who have sex with men and HIV/AIDS in sub-Saharan Africa. Smith AD, Tapsoba P, Peshu N, Sanders EJ, Jaffe H. Lancet. 2009;374: 416-422.

Globally, men who have sex with men continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of groups of men who have sex with men across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between men who have sex with men and heterosexual networks have been reported. Yet most African men who have sex with men have no safe access to relevant HIV information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV prevention and control programmes. The HIV community now has considerable challenges in clarifying and addressing the needs of men who have sex with men in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV requires improved strategic information about all risk groups, including men who have sex with men. The belated response to men who have sex with men with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

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 Editors’ note: Major barriers exist in access to effective HIV prevention, treatment, and care and support for men who have sex with men in sub-Saharan Africa. Not the least of these is the need for African political commitment to legal reforms and social protection for sexual minorities and those who work with them. It is not surprising that HIV subtypes in African men who have sex with men are similar to those occurring in the general population given that a high proportion of them report recent female sexual partners and many are married. What is surprising is how little is known about them. Only 17 of 52 African countries reported any information about risk knowledge and behaviour, HIV prevalence, and access to care among men who have sex with men in their 2008 reports of progress on the 2001 Declaration of Commitment. The silence must be broken to start to reverse the inaction that is so harmful to men who have sex with men, and to everyone else in Africa.

Health workers’ views on quality of prevention of mother-to-child transmission and postnatal care for HIV-infected women and their children. Nguyen TA, Oosterhoff P, Pham YN, Hardon A, Wright P. Hum Resour Health. 2009;13;7:39.

Prevention of mother-to-child transmission has been considered as not a simple intervention but a comprehensive set of interventions requiring capable health workers. Viet Nam’s extensive health care system reaches the village level, but still HIV-infected mothers and children have received inadequate health care services for prevention of mother-to-child transmission. Nguyen and colleagues report here the health workers’ perceptions on factors that lead to their failure to give good quality prevention of mother-to-child transmission services. Semistructured interviews with 53 health workers and unstructured observations in nine health facilities in Hanoi were conducted. Selection of respondents was based on their function, position and experience in the development or implementation of prevention of mother-to-child transmission policies/programmes. Factors that lead to health workers’ failure to give good quality services for prevention of mother-to-child transmission include their own fear of HIV infection; lack of knowledge on HIV and counselling skills; or high workloads and lack of staff; unavailability of HIV testing at commune level; shortage of antiretroviral drugs; and lack of operational guidelines. A negative attitude during counselling and provision of care, treating in a separate area, and avoidance of providing service at all were seen by health workers as the result of fear of being infected, as well as distrust towards almost all HIV-infected patients because of the prevailing association with antisocial behaviours. Additionally, the fragmentation of the health care system into specialized vertical pillars, including a vertical programme for HIV, is a major obstacle to providing a continuum of care. Many hospital staff were not able to provide good care or were even unwilling to provide appropriate care for HIV-positive pregnant women The study suggests that the quality of prevention of mother-to-child transmission service could be enhanced by improving communication and other skills of health workers, providing them with greater support and enhancing their motivation. Reduction of workload would also be important. Development of a practical strategy is needed to strengthen and adapt the referral system to meet the needs of patients.

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Editors’ note : This study was undertaken to find out the opinions of health care workers, who are subjected to many accusations about gaps and weaknesses in their performance, in Hanoi’s programme to prevent mother-to-child HIV transmission. The fragmentation of the health system, their own stigma from colleagues and family because of their exposure to HIV-infected patients, and their personal fear of HIV exposure in the absence of protective clothing and post-exposure kits all combine to reduce their motivation. They identified specific problems in their training and skills updating, a heavy workload, and a lack of equipment and materials. Remedying these will take varying lengths of time but seeking pragmatic solutions in the short term to produce tangible results could improve both the quality of patient care and the job satisfaction of health care personnel looking after them.

Early assessment of the implementation of a national programme for the prevention of mother-to-child transmission of HIV in Cameroon and the effects of staff training: a survey in 70 rural health care facilities. Labhardt ND, Manga E, Ndam M, Balo JR, Bischoff A, Stoll B. Trop Med Int Health 2009; 14: 288-93.

Labhardt and colleagues set out to assess the availability of equipment and the staff’s knowledge to prevent mother-to-child Transmission (PMTCT) in rural healthcare facilities recently covered by the national PMTCT programme in Cameroon. In eight districts inventories of antiviral drugs and HIV test kits were made on site, using a standardised check-list. Knowledge of HIV and PMTCT was evaluated with a multiple-choice questionnaire based on typical clinical PMTCT cases. Staff participated subsequently in a 2-day training on HIV and the Cameroon PMTCT guidelines. Immediately after training and after 7 months, retention of knowledge was tested with the same questions but in different order and layout. Sixty two peripheral nurse-led clinics and the eight district hospitals were assessed. Whereas all district hospitals presented complete equipment, only six of the peripheral clinics (10%) were equipped with both complete testing materials and a full set of drugs to provide PMTCT. Thirty six peripheral facilities (58%) possessed full equipment for HIV-testing and 8 (13%) stocked all PMTCT drugs. Of 137 nurses, 102 (74%) agreed to the two knowledge tests. Fewer than 66% knew that HIV-diagnosis requires positive results in two different types of rapid tests and only 19% chose the right recommendation on infant-feeding for HIV-positive mothers. Correct answers on drug regimens in different PMTCT settings varied from 25% to 56%. All percentages of correct answers improved greatly with training (P < 0.001) and retention remained high 7 months after training (P < 0.001). Programmes to prevent mother-to-child transmission in settings such as rural Cameroon need to be adapted to the special needs of peripheral nurse-led clinics. Appropriate short training may considerably improve nurses’ competence in PMTCT. Other important components are regular supervision and measures to guarantee supply of equipment in rural areas.

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Editors’ note: Cameroon has set an ambitious objective of increasing the proportion of pregnant women who have access to HIV counselling and testing services from 10% to 50% by 2010. This study, conducted four to eight months after HIV test kits and antiretroviral drugs were distributed to health districts, found inadequate supplies of materials and low levels of staff awareness and knowledge of proper procedures. A two-day training programme including case-based interactive discussions led to sustained improvement in assessment scores. Guaranteeing the flow of equipment to peripheral clinics and maintaining health care worker competence through training and supportive supervision, will be key if Cameroon is to meet its 2010 objective.