HIV This Week

Factors influencing global antiretroviral procurement prices.

Wirtz VJ, Forsythe S, Valencia-Mendoza A, Bautista-Arredondo S. BMC Public Health. 2009. 9 Suppl 1:S6.

Antiretroviral medicines are one of the most costly parts of HIV treatment. Many countries are struggling to provide universal access to antiretroviral medicines for all people living with HIV. Although substantial price reductions of antiretroviral medicines have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global antiretroviral prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on antiretroviral procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to antiretroviral treatment programs. An antiretroviral medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 antiretrovirals, global median prices and price variation were calculated. Linear regression models for each antiretroviral were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country's antiretroviral prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan for AIDS Relief. One of the principal mechanisms that can help to lower prices for antiretroviral medicines over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

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Editors’ note: There has been an unprecedented global effort to increase antiretroviral drug price transparency, including through the requirements of the Global Fund, the Clinton Initiative, and others for countries to report their pricing data. The Global Price Reporting Mechanism (GPRM) provides information on the prices that countries actually paid for antiretroviral medications through its publicly accessible database http://www.who.int/hiv/amds/gprm/en/. Analysis of the GPRM data debunks the assumptions that procuring larger volumes will reduce prices (that was true for only 2 of the 12 drugs studied) and that generic competition leads to equivalent innovator prices (only the second line innovator product lopinavir/ritonavir was associated with lower prices than generic products). Since there is tiered pricing or discounts for most antiretroviral drugs bought by low- and low-middle-income countries, with the exception of the entry inhibitor maraviroc, continued expansion of the GPRM to include data from all countries will increase long-term efficiency (best value for money) in antiretroviral drug procurement.

Galárraga O, Colchero MA, Wamai RG, Bertozzi SM. BMC Public Health. 2009. 9 Suppl 1:S5.

After more than 25 years, public health programs have not been able to sufficiently reduce the number of new HIV infections. Over 7,000 people become infected with HIV every day. Lack of convincing evidence of cost-effectiveness may be one of the reasons why implementation of effective programs is not occurring at sufficient scale. This paper identifies, summarizes and critiques the cost-effectiveness literature related to HIV-prevention interventions in low- and middle-income countries during 2005-2008. Systematic identification of publications was conducted through several methods: electronic databases, internet search of international organizations and major funding/implementing agencies, and journal browsing. Inclusion criteria included: HIV prevention intervention, year for publication (2005-2008), setting (low- and middle-income countries), and cost-effectiveness estimation (empirical or modeling) using outcomes in terms of cost per HIV infection averted and/or cost per disability-adjusted life year(DALY) or quality-adjusted life year (QALY). The authors found 21 distinct studies analyzing the cost-effectiveness of HIV-prevention interventions published in the past four years (2005-2008). Seventeen cost-effectiveness studies analyzed biomedical interventions; only a few dealt with behavioural and environmental/structural interventions. Sixteen studies focused on sub-Saharan Africa, and only a handful on Asia, Latin America and Eastern Europe. Many HIV-prevention interventions are very cost effective in absolute terms (using costs per DALY averted), and also in country-specific relative terms (in cost per DALY measured as percentage of GDP per capita). There are several types of interventions for which cost-effectiveness studies are still not available or are insufficient, including surveillance, abstinence, school-based education, universal precautions, prevention for positives and most structural interventions. The sparse cost-effectiveness evidence available is not easily comparable; thus, not very useful for decision making. More than 25 years into the HIV epidemic and billions of dollars of spending later, there is still much work to be done both on costs and effectiveness to adequately inform HIV prevention planning.

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Editors’ note: Cost-effectiveness analyses in HIV prevention can provide part of the information that decision-makers use to decide on the optimal mix of interventions to tailor to their epidemic context. Although available cost-effectiveness data show that many HIV prevention interventions are cost-effective, there are huge gaps in our knowledge. For example, there are no cost-effectiveness studies on prevention for and with positive people, for key populations at higher risk of HIV exposure in concentrated epidemics around the world, and for inmates or other captive populations. We lack cost-effectiveness data by epidemic type and scale-up scenario, as well as for a number of HIV prevention interventions that are considered standard components of national strategies. Cost-effectiveness analysis has several limitations and is not the ‘be all, end all’ in decision-making but it can usefully inform difficult choices.

Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples.

Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, Manongi R, Vwalika B, Celum C; for the Partners in Prevention HSV/HIV Transmission Study Team. AIDS. 2009. Dec [Epub ahead of print].

Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision. Data were collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used. A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, the authors observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1.

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Editors’ note: The trend seen here among 1096 couples toward a protective effect of male circumcision for HIV-negative women in discordant partnerships is intriguing. Sexual behaviours of couples with circumcised men were similar to those in which the man was not circumcised, only genetically-linked transmissions (i.e. transmissions within the couple) were considered (incidence 3.0 per 100 person years), and follow-up time after initiation of antiretroviral treatment (when viral loads presumably fell) was excluded. The result was a borderline statistically significant 47 per cent reduced risk of HIV-1 acquisition in women. Possible mechanisms that might explain lower risk for women are reduced risk of sexually transmitted infections in circumcised men or reduced likelihood of direct HIV transmission that would have otherwise occurred as a result of microtrauma or inflammation of the foreskin.

Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, Ravel J, Keim PS, Serwadda D, Wawer MJ, Gray RH., PLoS One. 2010. 5:e8422.

Circumcision is associated with significant reductions in HIV, HSV-2, and HPV infections among men and significant reductions in bacterial vaginosis among their female partners. The authors assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significantdecrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families they identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

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Editors’ note: Although molecular analyses have been used to characterise the microbiota or microbial community in the vagina, this is the first molecular assessment of the bacterial diversity found in the male genital mucosa. This pre-post circumcision study of 12 men shows that removing the foreskin removes the oxygen-poor environment of the mucosa under the foreskin that provides a warm, moist home for bacteria, many of which are anaerobic and are associated with bacterial vaginosis in women. This helps explain why the female partners of circumcised men have fewer sexually transmitted infections and less bacterial vaginosis. Getting rid of these bacteria through circumcision reduces mucosal inflammation and may provide part of the explanation for the reduced risk of HIV, herpes simplex-2, and human papilloma virus (HPV) infections in circumcised men.

Utility of a Point-of-Care Malaria Rapid Diagnostic Test for Excluding Malaria as the Cause of Fever among HIV-Positive Adults in Rural Rakai, Uganda.

Mills L, Kagaayi J, Nakigozi G, Galiwango R, Ouma J, Shott J, Ssempijja V, Gray R, Wawer M, Serwadda D, Quinn T, and Reynolds S. Am. J. Trop. Med. Hyg. 2010. 82:145-147.

Mills and colleagues compared results of a malaria rapid diagnostic test (Binax Now ® Malaria, Binax-M, Inverness Medical Innovations, Inc., Waltham, MA) performed at rural mobile clinics in Uganda by clinicians evaluating febrile adult HIV patients to thick smear evaluated at a central laboratory by trained microscopists. Two hundred forty-six samples were analyzed, including 14 (5.7%) which were thick-smear positive for falciparum malaria. Sensitivity of Binax-M compared with thick smear was 85.7% (95% CI: 57.2–98.2), specificity 97.8% (95% CI: 94.9–99.3), positive and negative predictive values were 70.6% (95% CI: 44.0–89.7) and 99.1% (95% CI: 96.8–99.9), respectively. The rapid diagnostic test accurately ruled malaria "in or out" at the point-of-care, facilitating appropriate clinical management and averting unnecessary anti-malarial therapy.

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Editors’ note: Through a PEPFAR-funded mobile HIV clinic programme, most participants in this study in a falciparum malaria endemic district in Uganda had received insecticide treated bed nets, cotrimoxasole prophylaxis regardless of CD4 count, and antiretroviral treatment if their CD4 counts fell below 250 cells/ µ l. With malaria suspected in 41.5% of general out-patient visits in this district, use of this point-of-care test in people living with HIV who presented with fever allowed health care providers to focus on other urgent causes of fever. The test had a high negative predictive value, meaning that a negative test was highly likely to mean that the person did not have malaria.

Effect of provider-initiated testing and counselling and integration of ART services on access to HIV diagnosis and treatment for children in Lilongwe, Malawi: a pre- post comparison.

Weigel R, Kamthunzi P, Mwansambo C, Phiri S, Kazembe PN. BMC Pediatr. 2009. 9(1):80.

The HIV prevalence in Malawi is 12 % and Kamuzu Central Hospital, in the capital Lilongwe, is the main provider of adult and paediatric HIV services in the central region. The Lighthouse at Kamuzu Central Hospital offers voluntary HIV testing and counselling for adults and children. In June 2004, Lighthouse was the first clinic to provide free antiretroviral treatment in the public sector, but few children accessed the services. In response, provider-initiated HIV testing and counselling and an antiretroviral treatment clinic were introduced at the paediatric department at Kamuzu Central Hospital in Quarter 4 (Q4) 2004. The authors analysed prospectively collected, aggregated data of quarterly reports from Q1 2003 to Q4 2006 from opt-in HIV testing and counselling centre registers, antiretroviral treatment registers and clinic registrations at the antiretroviral treatment clinics of both Lighthouse and the paediatric department. By comparing data of both facilities before (Q1 2003 to Q3 2004), and after the introduction of the services at the paediatric department (Q4 2004 to Q4 2006), they assessed the effect of this intervention on the uptake of HIV services for children at Kamuzu Central Hospital. Overall, 3971 children were tested for HIV, 2428 HIV-infected children were registered for care and 1218 started antiretroviral treatment. Between the two periods, the median (IQR) number of children being tested, registered and starting antiretroviral treatment per quarter rose from 101 (53-109) to 358 (318-440), 56 (50-82) to 226 (192-234) and 18 (8-23) to 139 (115-150), respectively. The median proportion of tested clients per quarter that were children rose from 3.8% (2.7-4.3) to 9.6% (8.8 to 10.0) (p=0.0009) and the proportion of antiretroviral treatment starters that were children rose from 6.9% (4.9-9.3) to 21.1% (19.2-24.2) (p=0.0036). The proportion of registered children and adults starting antiretroviral treatment each quarter increased similarly, from 26% to 53%, and 20% to 52%, respectively. Implementation of provider-initiated HIV testing and counselling and integration of antiretroviral treatment services within the paediatric ward are likely to be the main reasons for improved access to HIV testing and counselling and antiretroviral treatment for children at Kamuzu Central Hospital, and can be recommended to other hospitals with paediatric inpatients in resource limited settings with high HIV prevalence.

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Editors’ note: Even though providers initiated an offer of HIV testing and counselling with the caregivers of only 10% of admitted children at the Kamazu Central Hospital, there was a marked increase in the absolute numbers and proportions of children tested for HIV and started on antiretroviral treatment at this facility, compared to the era of parent/caregiver-initiated voluntary testing and counselling. It is unclear whether this modest increase in provider-initiated testing and counselling made the difference or whether it was the advent of free antiretroviral treatment that changed both client and health worker attitudes towards HIV counselling and testing. In any case, 41% of all children tested at the hospital were tested through the paediatric ward and the yield there was high, providing an additional entry point to antiretroviral treatment for children in Lilongwe.

"It's better not to know": perceived barriers to HIV voluntary counseling and testing among sub-Saharan African migrants in Belgium.

Manirankunda L, Loos J, Alou TA, Colebunders R, Nöstlinger C. AIDS Educ Prev. 2009. 21:582-93.

This study explored perceptions, needs, and barriers of sub-Saharan African migrants in relation to HIV voluntary counselling and testing. Using an inductive qualitative methodological approach, data were obtained from focus group discussions. Results showed that participants were in principle in favour of voluntary counselling and testing. However, they indicated that barriers outweighed advantages. Such barriers included fear of positive test results and its related personal and social consequences, lack of information, lack of preventive health behaviour, denial of HIV risk, and missed opportunities. Limited financial resources were only a concern for some subgroups like young people, asylum seekers, and recent migrants. This study identified multiple and intertwined barriers to voluntary counselling and testing from a community perspective. In order to promote voluntary counselling and testing, interventions such as raising awareness through culturally sensitive education should be adopted at community level. At level of service provision, provider initiated HIV testing including target group tailored counselling should be promoted.

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Editors’ note: This first qualitative community-based study of the barriers to uptake of voluntary counselling and testing among sub-Saharan migrants in Belgium found that previously acquired experiences in their countries of origin negatively influenced testing uptake. The images of relatives or friends, who had been ill and died of AIDS, shaped attitudes toward knowledge of serostatus, as did the considerable responsibilities that many recent migrants have toward family and community members back home. Focus group participants indicated that provider-initiated discussions of HIV testing, combined with the testimonies of people living with HIV and in good health on how to live with HIV, would help reduce fears of HIV testing and counselling. Efforts to reduce stigma, increase social support, and increase testing uptake in a culturally sensitive manner will increase the proportion of migrants wanting to learn their HIV status.