HIV This Week

Welcome to the forty-seventh issue of HIV This Week!  In this issue, we cover sexually transmitted infections (making the case for Trichomonas vaginalis control to reduce HIV incidence), injecting drug use (reaching a harm reduction coverage tipping point cuts HIV incidence by 75% in cross-border China and Viet Nam; HIV is not far behind for pseudo-ephedrine injectors in the Ukraine ), treatment (a randomised controlled trial in Rwanda reveals why we all should exercise, whether living with HIV or not), resources/impact/development (HIV-related costs and impacts for businesses less damaging than expected in South Africa, Uganda, Kenya, Zambia, Ethiopia, and Rwanda; how much of total treatment costs in Haïti are for generic antiretroviral drugs?), malaria and HIV (read this if you need to be convinced about cotrimoxazole prophylaxis for infants born to HIV-positive mothers and insecticide-treated bed nets), HIV testing (mothers respond enthusiastically to offers of point–of-care HIV testing in child health clinics in Mombasa, Kenya; need for a national HIV testing policy and programming framework in Turkey), private sector responses (virological results in a South African workplace treatment programme comparable to high-income countries; why the public sector has to step up to the plate for HIV prevention in most workplaces in Kenya, Uganda and Tanzania), basic science (avoiding subtype D – which subtypes make a difference to HIV progression?; what is an elite controller and would you want to be one?), and refugees (transactional sex in Congolese refugees in Tanzania; health protection and promotion for government assisted refugees in Canada).

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For full pdf access of this issue: HIV This Week Issue#47

Cate Hankins	Tania Lemay	Nicolai Lohse
Chief Scientific Adviser	Interim Research Officer	Research Officer

Van Der Pol B, Kwok C, Pierre-Louis B, Rinaldi A, Salata RA, Chen PL, van de Wijgert J, Mmiro F, Mugerwa R, Chipato T, Morrison CS. Trichomonas vaginalis Infection and Human Immunodeficiency Virus Acquisition in African Women. J Infect Dis. 2008;197(4):548-554.

Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide, with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However, its impact as a cofactor for HIV acquisition is poorly understood. Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study  involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls). All samples underwent polymerase chain reaction  (PCR) analysis for Trichomonas vaginalis DNA. For cases, analyzed samples were from the visit in which HIV seroconversion was detected and the visit preceding detection of seroconversion; for controls, one analyzed sample was from the visit matched by follow-up duration to the cases’ seroconversion visit, and the other sample was from the visit immediately preceding the matched visit. The prevalence of Trichomonas vaginalis infection before HIV infection was 11.3% in cases and 4.5% in controls. In multivariable analysis controlling for hormonal contraception, other STIs, behavioural, and demographic factors, the adjusted odds ratio for HIV acquisition was 2.74 (95% confidence interval, 1.25-6.00) for Trichomonas vaginalis-positive cases. The presence of behavioural risk factors for HIV infection, study recruitment from a referral population at high-risk for HIV, primary sex partner-associated risk for HIV infection, and herpes simplex virus type 2 seropositivity were also predictive of incident HIV infection. Trichomonas vaginalis infection is strongly associated with an increased risk for HIV infection in this general population of African women. Given the high prevalence of Trichomonas vaginalis infection in HIV-endemic areas, Trichomonas vaginalis control may have a substantial impact on preventing HIV acquisition among women.

Editors’ note: This first longitudinal study to measure the association between prevalent trichomonal infection and risk of HIV acquisition in a general population of women in family planning clinics has produced findings applicable to women of reproductive age worldwide. The link between bacterial sexually transmitted infections and HIV acquisition is unclear and control of herpes simplex virus-2, the most significant sexually transmitted risk factor for HIV acquisition, remains illusive. Even in the absence of inexpensive and easy to perform wet mount microscopy to detect trichomonas, aggressive treatment in high prevalence areas may be warranted. Detecting and treating trichomonas vaginalis in areas of high HIV prevalence could result in significant reduction in HIV spread.

Des Jarlais DC, Kling R, Hammett TM, Ngu D, Liu W, Chen Y, Binh KT, Friedmann P. Reducing HIV infection among new injecting drug users in the China-Vietnam Cross Border Project. AIDS. 2007;21 Suppl 8:S109-14.

Des Jarlais and colleagues aimed to assess an HIV prevention programme for injecting drug users (IDU) in the crossborder area between China and Vietnam. The project included peer educator outreach and the large-scale distribution of sterile injection equipment. Serial cross-sectional surveys with HIV testing of community recruited IDU were conducted at baseline (before implementation) and 6, 12, 18, 24 and 36 months post-baseline. HIV prevalence and estimated HIV incidence among new injectors (individuals injecting drugs for < 3 years) in each survey wave were the primary outcome measures. The percentages of new injectors among all subjects declined across each survey waves in both Ning Ming (China) and Lang Son (Vietnam). HIV prevalence and estimated incidence fell by approximately half at the 24-month survey and by approximately three quarters at the 36-month survey in both areas (all P < 0.01). The authors conclude that implementation of large-scale outreach and syringe access programmes was followed by substantial reductions in HIV infection among new injectors, with no evidence of any increase in individuals beginning to inject drugs. This project may serve as a model for large-scale HIV prevention programming for IDU in China, Vietnam, and other developing/transitional countries.

Editors’ note: Large-scale implementation of harm reduction programmes to reduce the risk of HIV exposure and transmission among injecting drug users (which include community outreach, needle and syringe access, and substitution treatment) have brought HIV epidemics under control in a number of high-income countries. This cross-border programme aimed to achieve public health scale implementation, considered as 7 to 10 syringes per injecting drug user per month, through direct syringe provision and no-cost vouchers to exchange for sterile injecting equipment and condoms in participating local pharmacies. Although the observed dramatic reduction in HIV incidence may be due in part to behaviour change motivated by the large number of AIDS deaths, increased access to sterile injecting equipment helped translate increased motivation into effective risk reduction. This study demonstrates that when harm reduction programmes are implemented at a scale commensurate to the size of the problem, they can turn around an HIV epidemic among injecting drug users in a developing or transitional country.

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Booth RE, Lehman WE, Kwiatkowski CF, Brewster JT, Sinitsyna L, Dvoryak S. Stimulant Injectors in Ukraine: The Next Wave of the Epidemic? AIDS Behav. 2008 Feb 9 [Epub ahead of print].

This study was designed to assess differences in drug and sex-related risk behaviours between injectors of opiates only, opiate/sedative mix only and stimulants only. Participants were current out-of-treatment injection drug users (IDUs), unaware of their HIV status, recruited through street outreach in Kiev, Odessa and Makeevka/Donetsk, Ukraine. Overall, 22% tested positive for HIV, including 39% among opiate/sedative injectors, 19% among opiate injectors and 17% among stimulant injectors. Despite these differences, stimulant injectors were at higher risk than other IDUs in sharing a used needle/syringe, always injecting with others, injecting a drug solution drawn from a common container, having an IDU sex partner, not using condoms during vaginal or anal sex and on composite measures of injection and sex risks. After controlling for age differences, stimulant injectors remained at higher risk in their needle and sex risk behaviours. Without intervention, it is likely that HIV will increase among stimulant injectors.

Editors’ note: Stimulant injectors in North America generally have higher HIV prevalence, second only to polydrug users, a population excluded from this study. Rather than cocaine, in the Ukraine context the stimulant is pseudo-ephedrine obtained through pharmacies and prepared for injection in a shared mixing container. Although they are younger and have lower HIV prevalence than other drug users, Ukrainian stimulant injectors have the sexual and injecting behaviours to set aflame the next wave of HIV in their country.

Mutimura E, Crowther NJ, Cade TW, Yarasheski KE, Stewart A.Exercise training reduces central adiposity and improves metabolic indices in HAART-treated HIV-positive subjects in Rwanda: a randomized controlled trial. AIDS Res Hum Retroviruses. 2008; 24(1):15-23.

As HAART becomes more accessible in sub-Saharan Africa, metabolic syndromes, body fat redistribution, and cardiovascular disease may become more prevalent. Mutimura and colleagues conducted a 6-month, randomized controlled trial to test whether cardiorespiratory exercise training (CET), improves metabolic, body composition and cardiorespiratory fitness parameters in HAART-treated HIV(+) African subjects with body fat redistribution (BFR). Persons with HIV and body fat redistribution were randomly assigned to exercise (HIV(+)BFR(+)EXS, N=50) or no exercise (N=50). These groups were compared with a group of persons with HIV but without BFR (N=50) and a group of persons without HIV (N=50). Six months of cardiorespiratory exercise training reduced waist circumference (-7.13 +/- 4.4 cm, p < 0.0001), waist-hip ratio (-0.10 +/- 0.1, p < 0.0001), sum skinfold thickness (-6.15 +/- 8.2 mm, p < 0.0001) and % body fat mass (-1.5 +/- 3.3, p < 0.0001) in HIV(+)BFR(+)EXS. Hip circumference was unchanged in non-exercise control groups.  Cardiorespiratory exercise training reduced fasting total cholesterol (-0.03 +/- 1.11 mM, p < 0.05), triglycerides (-0.22 +/-0.48 mM, p < 0.05) and glucose levels (-0.21 +/- 0.71 mM, p < 0.05) (p < 0.0001). HDL-, LDL-cholesterol and homeostasis model assessment values were unchanged after CET. Interestingly, HIV(+) subjects randomized to non-exercising groups experienced increases in fasting plasma glucose levels, whereas HIV seronegative  controls did not (p < 0.001). Predicted VO(2) peak increased more in the HIV(+)BFR(+)EXS than in all other groups (4.7 +/- 3.9 ml/kg/min, p < 0.0001). Exercise training positively modulated body composition and metabolic profiles, and improved cardiorespiratory fitness in HAART-treated HIV(+) Africans. These beneficial adaptations imply that exercise training is a safe, inexpensive, practical, and effective treatment for evolving metabolic and cardiovascular syndromes associated with HIV and HAART exposure in resource-limited sub-Saharan countries, where treatment is improving, morbidity and mortality rates are declining, but where minimal resources are available to manage HIV- and HAART-associated cardiovascular and metabolic syndromes.

Editors’ note: Minimal resources and medications (anti-hypertensives, anti-diabetics, anti-hyperlipidemics) are available to manage HIV-related and antiretroviral drug-associated metabolic syndromes and increased risk of cardiovascular disease in the many countries where antiretroviral treatment access is improving. This randomised controlled trial found that cardio-respiratory exercise led to considerable reductions in waist circumference, increases in lean body mass, and improved cardiovascular fitness in Rwandans with body fat alterations due to antiretroviral drugs. Exercise training is safe, practical, and efficacious ― we should all be doing more of it, whether we have HIV or not!

Rosen S, Feeley F, Connelly P, Simon J. The private sector and HIV/AIDS in Africa: taking stock of 6 years of applied research. AIDS 2007;21 Suppl 3:S41-51.

Until recently, little was known about the costs of the HIV epidemic to businesses in Africa or about business responses to the epidemic.  This paper synthesizes the results of a set of studies conducted between 1999 and 2006. Data for the studies included were drawn from human resource, financial, and medical records of 16 large companies and from 7 surveys of small, medium-sized, and large companies in South Africa, Uganda, Kenya, Zambia, Ethiopia, and Rwanda. The estimated workforce HIV prevalence ranged from 5 to 37%. The average cost per employee lost to AIDS varied from 0.5 to 5.6 times the average annual compensation of the employee affected. Labour cost increases were estimated at 0.6-10.8% but exceeded 3% at only two of 14 companies. Antiretroviral treatment at a cost of US$360/patient per year was found to have positive financial returns for most but not all companies. Managers of small and medium-sized enterprises (SME) reported low HIV-related employee attrition, little concern about the impacts of HIV, and relatively little interest in taking action. HIV was estimated to increase the average operating costs of small and medium-sized enterprises by less than 1%. In conclusion, for most companies, HIV is causing a moderate increase in labour costs, with costs determined mainly by HIV prevalence, employee skill level, and employment policies. Treatment of HIV-positive employees is a good investment for many large companies. Small companies have less capacity to respond to workforce illness and little concern about it. Research on the effectiveness of workplace interventions is needed.

Editors’ note: This synthesis suggests that well-designed interventions can achieve the double benefit of reducing costs to employers while improving the welfare of individual employees. Small and medium-sized companies face business challenges such as power failures, unpredictable taxes, and political instability, and are unable to benefit from economies of scale. Their HIV workplace programmes require support from business associations or external funders for HIV prevention activities and must rely on governments and non-governmental organizations for healthcare provision.

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Koenig SP, Riviere C, Leger P, Severe P, Atwood S, Fitzgerald D, Pape JW, Schackman BR. The cost of antiretroviral therapy in Haiti. Cost Eff Resour Alloc. 2008; 14;6(1):3.

Koenig and colleagues determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti. The authors examined data from 218 treatment-naive adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labour $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year.  The authors estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.

Editors’ note: Costing studies such as this one provide key information for programme management and budgeting, as well as hard data to feed into national, regional, and global cost estimates. Equity in treatment scale-up in Haiti and elsewhere will depend on keeping costs for first-and-second-line antiretroviral drugs low and developing innovative task-shifting scenarios for rural areas.

Malamba S, Hladik W, Reingold A, Banage F, McFarland W, Rutherford G, Mimbe D, Nzaro E, Downing R, Mermin J. The effect of HIV on morbidity and mortality in children with severe malarial anaemia. Malar J 2007;6:143.

Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed. In the study methods, children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children.  Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders. Results showed that, of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). Children living with HIV were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30-6.29, P=0.009) and within 28 days (HR = 3.70, 95% CI 1.91-7.17, P<0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54-9.16, P<0.001) compared to HIV-uninfected children.  Children living with HIV had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41-9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 - 6.07, P = 0.02) post-transfusion than HIV-uninfected children. In conclusion, children living with HIV with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.

Editors’ note: Repeated childhood exposures to malaria act on cellular immune function to generate partial immunity. Impaired cellular immunity due to HIV infection impedes clearance of malaria parasites and increases the risk of complications requiring hospitalization. With 90% of the world’s children living with HIV residing in Africa, many in malaria endemic areas, action is required to initiate cotrimoxazole prophylaxis at birth for all babies born to HIV-positive mothers, to educate parents about febrile episodes in their HIV-infected children, and to ensure that they benefit from the insecticide-treated bed nets that reduce malaria by 50%.

Chersich MF, Luchters SM, Othigo MJ, Yard E, Mandaliya K, Temmerman M. HIV testing and counselling for women attending child health clinics: an opportunity for entry to prevent mother-to-child transmission and HIV treatment. Int J STD AIDS. 2008 Jan;19(1):42-6.

This study assessed the potential for HIV testing at child health clinics to increase knowledge of HIV status, and entry to infant feeding counselling and HIV treatment. At a provincial hospital in Mombasa, Kenya, HIV testing and counselling were offered to women bringing their child for immunization or acute care services. Most women said HIV testing should be offered in these clinics (472/493, 95.7%), with many citing the benefits of regular testing and entry to prevent mother-to-child transmission. Of 500 women, 416 (83.4%) received test results, 97.6% on the same day. After 50 participants, point-of-care testing replaced laboratory-based rapid testing. Uptake increased 2.6 times with point-of-care testing (95% confidence interval = 1.4-5.1; P = 0.003). Of 124 women who had not accessed HIV testing during pregnancy, 98 tested in the study (79.0%). Measured by uptake and attitudes, HIV testing in child health clinics is acceptable. This could optimize entry into HIV treatment, infant feeding counselling and family planning services.

Editors’ note: One in four women in this study had not accessed HIV testing during pregnancy, limiting their access to antenatal, perinatal, and post-partum HIV prevention services. Offering HIV testing for mother and father at well-baby clinics and paediatric acute care services can identify babies that have been exposed to HIV infection for cotrimoxazole prophylaxis and assist parents with unmet needs for family planning, an important component (prong 2) of prevention of mother-to-child transmission programmes. If current trials of antiretroviral prophylaxis during breastfeeding prove it is effective, there will be yet another benefit of post-partum HIV testing and counselling.

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Ersoy N, Akpinar A. Attitudes about prenatal HIV testing in Turkey. Nurs Ethics. 2008 Mar;15(2):222-33.

The aim of this study was to assess the attitudes of Turkish pregnant women and antenatal health care providers towards prenatal HIV testing. A self-administered questionnaire was used. The relationships between the different groups’ knowledge and attitudes were analysed by using the chi-squared statistic. A total of 494 pregnant women and 181 care providers participated. Forty-four per cent of the pregnant women thought that prenatal HIV testing should be mandatory, and 84% of the health care providers thought it should be performed routinely or be mandatory. The majority of the pregnant women (74%) and half of the care providers agreed that the test results should be disclosed first to the pregnant woman. The study results also revealed that most of the prenatal care providers would not protect pregnant women’s autonomy and privacy, contrary to the pregnant women’s own preferences. It is essential to establish national prenatal HIV testing policies in order to prevent unethical practices and ensure satisfaction for pregnant women and health care providers.

Editors’ note: These discrepancies in the attitudes of prenatal care providers and pregnant women are striking and underscore the importance of Turkey moving now to establish a national policy and programming framework for client-initiated and provider-initiated HIV testing. Protecting the autonomy and privacy of pregnant women, preventing discrimination and stigmatisation of those found to be HIV-positive, providing treatment and care, and agreeing on choices for serostatus disclosure are among the key elements of such a framework.

Charalambous S, Innes C, Muirhead D, Kumaranayake L, Fielding K, Pemba L, Hamilton R, Grant A, Churchyard GJ. Evaluation of a workplace HIV treatment programme in South Africa. AIDS 2007;21 Suppl 3:S73-8.

Charalambous and colleagues aimed to review the experience of implementing a workplace HIV care programme in South Africa and describe treatment outcomes in sequential cohorts of individuals starting antiretroviral therapy (ART). The authors reviewed an industrial HIV care and treatment programme. Between October 2002 and December 2005, 2262 patients enrolled in the HIV care programme. CD4 cell counts increased by a median of 90, 113 and 164 cells/microl by 6, 12 and 24 months on treatment, respectively. The viral load was suppressed below 400 copies/ml in 75, 72 and 72% of patients at 6, 12 and 24 months, respectively, at an average cost of US$1654, 3567 and 7883 per patient virally suppressed, respectively. Treatment outcomes in sequential cohorts of patients were consistent over time. A total of 93.6% of patients at 14,752 clinic visits reported missing no tablets over the previous 3 days. Almost half the patients (46.8%) experienced one or more adverse events, although most were mild (78.7%). By the end of December 2005, 30% of patients were no longer on ART, mostly because of defaulted or stopped treatment (12.8%), termination of employment (8.2%), or death (4.9%). The authors conclude that this large workplace programme achieved virological results among individuals retained in the programme comparable to those reported for developed countries and that  more work is needed to improve retention. Monitoring treatment outcomes in sequential cohorts is a useful way of monitoring programme performance. As the programme has matured, the costs of programme implementation have reduced. Counselling is a central component of an ART programme. Challenges in implementing a workplace ART programme are similar to the challenges of public-sector programmes.

Editors’ note: Cohort studies such as this one can provide valuable information on retention rates and treatment outcomes over time which can be used to improve programme performance. Although virological outcomes in this large workplace programme were comparable with those of programmes in resource-poor and resource-rich countries, termination of employment led 8% of patients to stop antiretroviral treatment. Providing bridging treatment until patients are transferred to another HIV treatment programme ensures continuity of care without the unstructured treatment interruptions that can encourage disease progression and drug resistance.

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Ramachandran V, Shah MK, Turner GL. Does the private sector care about AIDS? Evidence from firm surveys in East Africa. AIDS 2007;21 Suppl 3:S61-72.

Ramachandran and colleagues aimed to identify determinants of HIV prevention activity and pre-employment health checks by private firms in Kenya, Uganda and Tanzania. The authors used data from the World Bank Enterprise Surveys for Uganda, Kenya and Tanzania, encompassing 860 formally registered firms in the manufacturing sector. Econometric analysis of firm survey data was used to identify the determinants of HIV prevention including condom distribution and voluntary counselling and testing (VCT). Multivariate regression analysis was the main tool used to determine statistical significance. The results showed that approximately a third of enterprises invest in HIV prevention. Prevention activity increases with size, most likely because larger firms and firms with higher skilled workers have greater replacement costs. Even in the category of larger firms, less than 50% provide VCT. The authors found that the propensity of firms to carry out pre-employment health checks of workers also varies by the size of firm and skill level of the workforce. Finally, data from worker surveys showed a high degree of willingness on the part of workers to be tested for HIV in the three East African countries.

Editors’ note: This study found that larger firms, those with trained workers or workers with higher skill levels, or those with unionized workers do more to prevent HIV. Given the high proportion of small companies compared to large ones in African countries, the public sector needs to take the lead on HIV prevention in most workplaces.

Kiwanuka N, Laeyendecker O, Robb M, Kigozi G, Arroyo M, McCutchan F, Eller LA, Eller M, Makumbi F, Birx D, Wabwire-Mangen F, Serwadda D, Sewankambo NK, Quinn TC, Wawer M, Gray R. Effect of Human Immunodeficiency Virus Type 1 (HIV-1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV-1 Infection. J Infect Dis. 2008 Feb 11 [Epub ahead of print].

Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. Kiwanuka and colleagues determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4(+) cell count were determined. Cox proportional hazards regression modelling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4(+) cell count of </=250 cells/mm(3)) and to AIDS-associated death. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years). Relative to subtype A, adjusted hazard rations of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71-11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. HIV disease progression is affected by HIV-1 subtype. This finding may affect decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression.

Editors’ note: Subtype does matter ― subtype D has a higher frequency of syncytium formation and of the CXCR4 receptor use which is associated with more rapid decreases in CD4 cell count. Infection with multiple subtypes also was associated with faster disease progression compared to infection with a single subtype, emphasising the importance of positive prevention to avoid super-infection. Future therapeutic HIV vaccine trials should assess subtype specific responses; however, current treatment programmes, with subtype analysis remaining a research and surveillance tool, will have to continue to initiate antiretroviral treatment using standard thresholds for everyone, regardless of subtype.

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Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, Baker B, Trocha A, Rosenberg R, Mackey E, Ueda P, Lu Z, Cohen D, Wrin T, Petropoulos CJ, Rosenberg ES, Walker BD. Genetic and Immunologic Heterogeneity among Persons Who Control HIV Infection in the Absence of Therapy. J Infect Dis. 2008 Feb 15;197(4):563-571.

Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies. HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIV-infected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of < 50 RNA copies/mL (elite controllers), those with levels of 50-2000  copies/mL (viremic controllers). Pereyra and colleagues also examined HIV-specific T cell and antibody responses as well as host genetics for patients with levels of >10,000 copies/mL (chronic progressors). CD8+ T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-gamma and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia. Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.

Editors’ note: The CD8 T cells of elite controllers appear to have enhanced ability to inhibit virus replication in vitro. Elite controllers have the highest ratio of functional CD4 to CD8 T cells (chronic progressors have the lowest). Whether this association between T cell function and HIV is cause or effect is unclear. The lower neutralising antibody activity seen in elite controllers suggests that neutralising antibodies do not play a major role in maintaining viral suppression in people who spontaneously control viral replication.

Tanaka Y, Kunii O, Hatano T, Wakai S. Knowledge, attitude, and practice (KAP) of HIV prevention and HIV infection risks among Congolese refugees in Tanzania. Health Place. 2007 Sep 21; [Epub ahead of print].

Little is known about HIV infection risks and risk behaviours of refugees living in resource-scarce post-emergency phase camps in Africa. This study at Nyarugusu Camp in Tanzania, covering systematically selected refugees (n=1140) and refugees living with HIV (PLHIV) (n=182), revealed that the level of HIV risk of systematically selected refugees increased after displacement, particularly regarding the number having transactional sex for money or gifts, while radio broadcast messages are perceived to promote a base of risk awareness within the refugee community. While condoms are yet to be widely used in the camp, some refugees having transactional sex tended to undertake their own health initiatives such as using a condom, under the influence of peer refugee health workers, particularly health information team members. Nevertheless, PLHIV were less faithful to one partner and had more non-regular sexual partners than the group without HIV. The study revealed that community-based outreach by refugee health workers is conducive to risk behaviour prevention in the post-emergency camp setting. It is recommended to increase the optimal use of « radio broadcast messages » and « health information team, » which can act as agents to reach out to wider populations, and to strengthen the focus on safer sex education for PLHIV; the aim being to achieve dual risk reduction for both refugees living with and without HIV.

Editors’ note: This study found that 18.8% of female refugees and 24.7% of male refugees were involved in transactional sex in the preceding 12 months. Fellow Congolese refugees represented the principal transactional sex partners for both males and females, with persons from local Tanzanian communities ranking second for men while police and humanitarian workers ranked second and third, respectively, in the case of women and adolescent girls 15 years of age and older. Condom use was low but significantly more likely in transactional sex, suggesting that the community outreach and peer education, which are having effect in this post emergency phase refugee camp, should be reinforced.

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Pottie K, Janakiram P, Topp P, McCarthy A. Prevalence of selected preventable and treatable diseases among government-assisted refugees: Implications for primary care providers. Can Fam Physician 2007;53:1928-34.

This retrospective cohort study aimed to discover the prevalence of 4 preventable and treatable diseases among newly arriving refugees. The study was, conducted at an immigrant-friendly family medicine centre in Ottawa, Ontario, Canada that offers newly arriving refugees a clinical preventive programme following a specially designed protocol. A total of 112 adult government-assisted refugees seen during 2004 and 2005, within 6 months of their arrival, were included. The main outcome measures were demographic information and prevalence of HIV infection, latent tuberculosis (TB), chronic hepatitis B surface antigen-positive status, and intestinal parasites. 71% of the adults were younger than 35 years and 83% of them had come from sub-Saharan Africa. Disease prevalence rates were 6.3% for HIV (95% confidence interval [CI] 1.8 to 10.8), 49.5% for latent TB (95% CI 39.5 to 49.8), 5.4% for chronic hepatitis B surface antigen-positive status (95% CI 1.2 to 9.5), and 13.6% for intestinal parasites (95% CI 7.2 to 20.0). Most refugees (83%) successfully completed the preventive care programme. Performing chi squared analysis revealed a statistically significant higher risk of latent TB among the men (P < .032). Most of the women had never had a Papanicolaou test. In conclusion, refugees are a vulnerable population with unique, but often preventable or treatable, health issues. This study demonstrated substantial differences in the prevalence of HIV, TB, chronic hepatitis B, and intestinal parasites between government-assisted refugees and Canadian residents. These health disparities and the emerging field of health settlement are new challenges for family physicians and other primary health care providers.

Editors’ note: In 2002 Canada waived the burden-of-illness barriers for refugees who have fled their countries of origin because of well-grounded fears of persecution. Such refugees have higher disease prevalences than the recipient population for HIV, latent TB, chronic hepatitis B surface antigen, and intestinal parasites, reflecting rates in their countries of origin. Health assessments, immunization, and health promotion, including cervical screening for cancer, are key to enhancing the health of all populations, including the government-assisted refugees described in this study.