HIV This Week

Nakakeeto ON , Kumaranayake L. The global strategy to eliminate HIV infection in infants and young children: a seven-country assessment of costs and feasibility. AIDS. 2009 May;23(8):987-95.

The objective of this study was to model the feasibility and affordability of the 2001 United Nations General Assembly Special Session on AIDS (UNGASS) goals to reduce mother-to-child transmission of HIV (MTCT) by 50% by 2010 and achieve 80% coverage of interventions to reduce it among women presenting for antenatal care. The cost and human resource needs of prevention of MTCT (PMTCT) and paediatric treatment were modelled for 2007-2015 and compared with the AIDS budgets and available health workforce in Burkina Faso, Cameroon, Cote d’Ivoire, Malawi, Rwanda, United Republic of Tanzania, and Zambia. Interventions used were promotion of family planning to people living with HIV, HIV testing and counselling, antiretroviral treatment to prevent MTCT and for HIV-infected children, and cotrimoxazole prophylaxis for mothers with advanced HIV infection and HIV-exposed children. The cumulative cost from 2007 to 2015 of the intervention in the seven countries combined amounted to US$587 688 291, 86% for PMTCT and 14% for paediatric treatment. Three out of the seven countries - Rwanda, Zambia, and Burkina Faso (almost) - were predicted to have sufficient AIDS funding, but only one - Zambia - was predicted to have also sufficient human resources to scale up the interventions by 2010 and sustain them up to 2015. The cost-effectiveness would be less than US$1150 per infection prevented in fully scaled-up programmes. Scaling up PMTCT will require more funds than currently available in many countries, but human resources appear to be a greater bottleneck than funding. The authors suggest that human resource capacity be assessed when increased funds for PMTCT are requested.

Editors’ note: Although these projections do not include primary prevention of HIV transmission to women of childbearing age, they do include the cost of addressing unmet family planning need among women with HIV who are of reproductive age and living in union. The model also estimated funding requirements to prevent mother-to-child transmission with antiretroviral prophylaxis, treat mothers in need of antiretroviral treatment for 9 months after the birth during breastfeeding, and treat infected children for 2 years. Although commodities (drugs, diagnostics, and supply chain management) represent 81% of the funds required and human resources represent 14%, it is the lack of sufficient numbers of health workers to implement the programme that is a major impediment in 6 of these countries striving to achieve the UNGASS goals of a 50% reduction in the incidence of HIV infection in infants by 2010.

The HIV epidemic continues to be a major issue facing Botswana, with overall adult HIV prevalence estimated to be 25.7 percent in 2007. This paper estimates the cost and impact of the draft Ministry of Health male circumcision strategy using the Decision-Makers' Programme Planning Tool (DMPPT). Demographic data and HIV prevalence estimates from the recent National AIDS Coordinating Agency estimations are used as input to the DMPPT to estimate the impact of scaling-up male circumcision on the HIV epidemic. These data are supplemented by programmatic information from the draft Botswana National Strategy for Safe Male Circumcision, including information on unit cost and program goals. Alternative scenarios were developed in consultation with stakeholders. Results suggest that scaling-up adult and neonatal circumcision to reach 80% coverage by 2012 would result in averting almost 70,000 new HIV infections through 2025, at a total net cost of US$47 million across that same period. This results in an average cost per HIV infection averted of US$689. Changing the target year to 2015 and the scale-up pattern to a linear pattern results in a more evenly-distributed number of male circumcisions required, and averts approximately 60,000 new HIV infections through 2025. Other scenarios explored include the effect of risk compensation and the impact of increasing coverage of general prevention interventions. Scaling-up safe male circumcision has the potential to reduce the impact of HIV in Botswana significantly; program design elements such as feasible patterns of scale-up and inclusion of counselling are important in evaluating the overall success of the program.

Editors’ note: Policy development and programme planning processes for the scale-up of safe male circumcision services for heterosexual men in high HIV prevalence settings are enhanced by the use of this decision-makers’ programme planning tool developed by the Futures Institute in collaboration with UNAIDS. Both Botswana and Namibia have used the tool and several other countries have already or are currently conducting the costing studies that provide key inputs to determine future costs and the impact of male circumcision service scale-up on their HIV epidemics.

Müller V, von Wyl V, Yerly S, Böni J, Klimkait T, Bürgisser P, Ledergerber B, Günthard HF, Bonhoeffer S; the Swiss HIV Cohort Study. African descent is associated with slower CD4 cell count decline in treatment-naive patients of the Swiss HIV Cohort Study. AIDS. 2009 May 20. [Epub ahead of print]

Miller and colleagues investigated the effect of descent (African versus European) on the progression of untreated HIV infections in a prospective cohort study of HIV-1-infected individuals. They estimated the linear rate of decline of the CD4 cell count and the setpoint viral load in patients with sufficient data points. The effect of descent was assessed by multivariate regression models including descent, sex, viral subtype, the earliest date of confirmed infection, age, and the baseline CD4 cell count; the rate of CD4 cell count decline was also analyzed with mixed-effect models and with matched comparisons between patients of African and European descent based on the baseline CD4 cell count. The authors found that the decline slope of the CD4 cell count was significantly less steep (+26.6 cells/mul per year; 95% confidence interval, 12.3-41.0; P < 0.001) in patients of African descent (n = 123) compared with patients of European descent (n = 463), and this effect was independent of differences in the infecting viral subtypes. Matched comparisons confirmed the effect of African descent (P < 0.001). Remarkably, the rate of CD4 cell count decline depended strongly on the viral setpoint in patients of European descent (-46.3 cells/microl per year/log10 RNA copies/ml; 95% confidence interval, -55.8 to -36.7; P < 0.001) but not in patients of African descent. Slower disease progression in patients of African descent might be related to host factors allowing better tolerance of high virus levels in patients of African descent compared with patients of European descent.

Editors’ note: Faster rates of HIV disease progression have been associated with immune activation. Even HIV-negative Africans have evidence of increased immune activation, likely due to prevalent co-infections. Comparing HIV–infected individuals of African and European descent who are exposed to the same low-antigen environment of Switzerland can narrow down differences in disease progression to viral and host factors. This study found no effect of viral sub-type suggesting that host factors must be key in the slower CD4 count decline observed in people of African origin living with HIV in Switzerland. Perhaps it is the lack of Duffy antigen receptors for chemokines (DARC-negative status) on the red blood cells in patients of African descent (see Weijing et al in HIV This Week issue 56).

Crum-Cianflone N, Eberly L, Zhang Y, Ganesan A, Weintrob A, Marconi V, Barthel RV, Fraser S, Agan BK, Wegner S. Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985-2007. Clin Infect Dis. 2009 May;48(9):1285-92.

Whether human immunodeficiency virus (HIV) seroconverters have been presenting with progressively lower CD4 cell counts over the course of the HIV epidemic is controversial. Additional data on whether HIV might have become more virulent on a population level (measured by post-seroconversion CD4 cell counts) may provide important insights regarding HIV pathogenesis. To determine whether post-seroconversion CD4 cell counts have changed over time, Crum-Cianflone and colleagues evaluated 2174 HIV seroconverters as part of a large cohort study during the period 1985-2007. Participants were documented antiretroviral-naive HIV seroconverters who had a CD4 cell count measured within 6 months after receiving a diagnosis of HIV infection. Multiple linear regression models were used to assess trends in initial CD4 cell counts. The mean initial CD4 cell count decreased during the study period from 632 cells/mm(3) in 1985-1990 to 553 cells/mm(3) in 1991-1995, 493 cells/mm(3) in 1996-2001, and 514 cells/mm(3) in 2002-2007. During those periods, the percentages of seroconverters with an initial CD4 cell count <350 cells/mm(3) were 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean decrease in CD4 cell count from 1985-1990 was 65 cells/mm(3) in 1991-1995 (P < .001), 107 cells/mm(3) in 1996-2001 (P < .001), and 102 cells/mm(3) in 2002-2007 (P < .001). Similar trends occurred with regard to CD4 cell percentage and total lymphocyte count. Similar decreases in initial CD4 cell counts were observed among African American and white persons during the epidemic. A significant decrease in initial CD4 cell counts among HIV seroconverters in the United States has occurred during the HIV epidemic. These data provide an important clinical correlate to suggestions that HIV may have adapted to the host, resulting in a more virulent infection.

Editors’ note: The findings for this large incident cohort (i.e. with a known date of seroconversion), in which 93% had a CD4 cell count measured within 3 months of seroconversion, suggest that initial CD4 counts among seroconverting military men (96% of the cohort were men) declined early in the HIV epidemic in the USA. Possible explanations include changes in the host, virus, or environment over time. Because the decline stabilized after introduction of potent antiretroviral therapy in 1996, it is plausible that treatment has stimulated a loss of viral fitness and diversity. The findings in the literature are conflicting and there are insufficient data to warrant a change in the assumptions about disease progression used in epidemiological modelling. Therefore further studies of the complexities of HIV virulence and host susceptibility are clearly warranted.

Mate KS, Bennett B, Mphatswe W, Barker P, Rollins N. Challenges for routine health system data management in a large public programme to prevent mother-to-child HIV transmission in South Africa. PLoS ONE. 2009;4(5):e5483. 

Recent changes to South Africa’s prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. Mate and colleagues assessed the completeness and accuracy of routine PMTCT data submitted to the District Health Information System in three districts of Kwazulu-Natal province, South Africa. They surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, they reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the District Health Information System. Data elements were reported only 50.3% of the time and were “accurate” (i.e. within 10% of reconstructed values) 12.8% of the time. The data element “Antenatal Clients Tested for HIV” was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while “HIV PCR testing of baby born to HIV positive mother” was the least accurate with only 5.3% of clinics meeting the definition of accuracy. Data collected and reported in the public health system across three large, high HIV-prevalence districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality.

Editors’ note: Beyond the finding of data missing at source, the weakest link in this data chain is the actual data collation at the clinic level, followed by lack of submission of data to the district level. Unless health workers are supported and supervised in the execution of data management tasks and unless data collection is designed in the first instance to be used locally to improve patient care, front line staff will not have the capacities nor perceive the value of data collection. Effective health information systems are simple, acceptable, timely, accurate, flexible, and useful. Only then do staff, who can improve clinical practice locally through analysis of performance and outcomes data, truly value them. This foundation stone is key to a health information system that helps national health systems assess progress towards established goals and plan future resource allocations.

Buse K, Lalji N, Mayhew SH, Imran M, Hawkes SJ. Political feasibility of scaling-up five evidence-informed HIV interventions in Pakistan: a policy analysis. Sex Transm Infect. 2009 Apr;85 Suppl 2:ii37-42.

Drawing on policy theories, an assessment was made of the perceived political feasibility of scaling-up five evidence-based interventions to curb Pakistan's HIV epidemic: needle and syringe exchange programmes; targeted behaviour change communication; sexual health care for male and transgender sex workers; sexual and reproductive health care for female sex workers; and promoting and protecting the rights of those at greatest risk. A questionnaire was emailed to 40 stakeholders and completed by 22. They expressed their level of agreement with 15 statements for each intervention (related to variables associated with policy success). Semi-structured interviews were conducted with 12 respondents. The interventions represent considerable change from the status quo, but are perceived to respond to widely acknowledged problems. These perceptions, held by the HIV policy elite, need to be set in the context of the prevailing view that the AIDS response is not warranted given the small and concentrated nature of the epidemic and that the interventions do not resonate closely with values held by society. The interventions were perceived to be evidence-based, supported by at least one donor and subject to little resistance from frontline staff as they will be implemented by contracted non-government organisations. The results were mixed in terms of other factors determining political feasibility, including the extent to which interventions are easy to explain, exhibit simple technical features, require few additional funds, are supported and not opposed by powerful stakeholders. The interventions stand a good chance of being implemented although they depend on donor support. The prospects for scaling them would be improved by ongoing policy analysis and strengthening of domestic constituencies among the target groups.

Editors’ notes: The complex interactions among institutions, interest groups, and ideas that result in policy and policy change are the subject of policy analysis. It explains why some issues, problems, or solutions grab the attention of policy-makers. This policy analysis based on a key-informant survey suggests that while evidence contributing to the knowledge base is important, often it is superseded by the arguments and stories that resonate with decision-makers and influence their values and beliefs. Supporting the development of constituencies among highly stigmatised key populations most in need of HIV prevention and treatment services could provide a voice for the stories that can change the minds of decision-makers in Pakistan.