HIV This Week

Suicide in HIV-Infected Individuals and the General Population in Switzerland, 1988-2008.

Keiser O, Spoerri A, Brinkhof MW, Hasse B, Gayet-Ageron A, Tissot F, Christen A, Battegay M, Schmid P, Bernasconi E, Egger M; for the Swiss HIV Cohort Study and the Swiss National Cohort. Am J Psychiatry. 2010. 167:143-150.

High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of antiretroviral therapy has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-antiretroviral treatment (1988-1995) and antiretroviral treatment (1996-2008) eras in HIV-infected patients and the general population in Switzerland. The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. They calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide. From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0-17.0) in the pre-antiretroviral treatment era to 3.5 (95% CI=2.5-4.8) in the late antiretroviral treatment era. In women, ratios declined from 11.6 (95% CI=6.4-20.9) to 5.7 (95% CI=3.2-10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide. Suicide rates decreased significantly with the introduction of antiretroviral treatment, but they remain above the rate observed in the general population, and risk factors for suicide remain similar.

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Editors’ note: The results of this study, revealing encouraging declines in the suicide rate among people living with HIV in Switzerland since the advent of antiretroviral treatment, need to be seen in context. Swiss suicide rates are in the top-third in Europe and the top quintile, i.e the top 20%, in the world. Declines in the suicide rate have occurred in the general population too but not to the extent seen in surrounding countries. Switzerland has no national suicide prevention programme to address this important public health problem and the suicide rate among people living with HIV, despite the important declines documented here, may be higher than in other European countries. They are certainly higher than in the general Swiss population and are higher than those in other patients with life-threatening conditions. Although 75% of people with HIV who committed suicide had a diagnosis of mental illness, it is unclear to what extent stigma, discrimination, social isolation, drug toxicity, and other factors are playing roles. Understanding what is influencing decisions to commit suicide is the first step to preventing such unnecessary deaths among people living with HIV.

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.

Deschamps MM, Noel F, Bonhomme J, Dévieux JG, Saint-Jean G, Zhu Y, Wright P, Pape JW, Malow RM. Prevention of mother-to-child transmission of HIV in Haiti. Rev Panam Salud Publica. 2009;25:24-30.

Deschamps and colleagues set out to describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in a mother-to-child transmission prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. Complete data were available for 348 mother-infant pairs who completed the program to prevent mother-to-child transmission of HIV. The rate of mother-to-child transmission in the study was 9.2% (95% CI:6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early paediatric diagnosis and antiretroviral treatment. The mother-to-child transmission prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.

Editors’ note: Over the period from 1999 to 2004 the annual number of women who agreed to undergo HIV testing at the GHESKIO clinic more than doubled and the number of HIV-positive women who enrolled in the prevention of mother-to-child transmission (PMTCT) programme quadrupled. Overall 43,173 women at higher risk of HIV exposure were tested (18.3% were HIV-positive) and 5270 were pregnant (12.3% HIV-positive). Of the 650 HIV-positive pregnant women, 28.7% did not participate in the PMTCT programme, primarily because they returned to rural areas, and only 14% were able to bring their partners in for HIV testing. After delivery, 73.9% of the women were using family planning services at 18-month follow-up compared to national uptake data of 23%. Despite persistent instability and violence in Haiti, this programme in Port-au-Prince has successfully reduced HIV transmission to infants to one-third of the historical rate. With a 2007 adult (15-49 years) HIV prevalence of 2.2% (1.9-2.5), in a league with the Bahamas, Guyana, Suriname, and Belize in the Americas, Haiti clearly needs a nationwide programme integrating family planning, voluntary counselling and testing, and HIV treatment services with good referral links between centres.

Cailhol J, Jourdain G, Coeur SL, Traisathit P, Boonrod K, Prommas S, Putiyanun C, Kanjanasing A, Lallemant M; for the Perinatal HIV Prevention Trial Group. Association of Low CD4 Cell Count and Intrauterine Growth Retardation in Thailand. J Acquir Immune Defic Syndr. 2009; 50:409-413.

Each year, intrauterine growth retardation affects 20-30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with intrauterine growth retardation. Some studies have suggested that HIV infection could increase the risk of intrauterine growth retardation. To confirm this hypothesis, Cailhol and colleagues examined the association between HIV-related factors and the risk of intrauterine growth retardation in Thailand. Data from a cohort of 1436 HIV-infected pregnant women enrolled in the « Perinatal HIV Prevention Trial-1 », a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with intrauterine growth retardation. The rate of intrauterine growth retardation was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with intrauterine growth retardation (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03). The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of intrauterine growth retardation. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of intrauterine growth retardation.

Editors’ note: Intrauterine growth retardation (IUGR) is the second cause of perinatal mortality after prematurity. It is associated with higher susceptibility to various conditions in the neonatal period as well as with diseases in adulthood such as diabetes, obesity, and hypertension. This Thai study used the stringent definition of IUGR of ‘birth weight below the 10 th percentile of weight for the corresponding gestational age’, rather than the low birth weight cut-off of 2500 g which can indicate prematurity. Also it used CD4 percentage which is less variable than absolute CD4 count. The finding that CD4 percentage below the median contributed 28% of the risk of IUGR in this population gives added support to the recommendation to initiate antiretroviral treatment (as opposed to antiretroviral prophylaxis) in pregnancy for women with low CD4 counts.

Stringer EM, Levy J, Sinkala M, Chi BH, Matongo I, Chintu N, Stringer JS. HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial. AIDS. 2009 ;23(11):1377-82 14.

HIV-infected women need access to safe contraception. Stringer and colleagues hypothesized that women using depomedroxyprogesterone acetate (DMPA) contraception would have faster HIV disease progression than women using oral contraceptive pills and nonhormonal methods. In a previously reported trial, the authors randomized 599 HIV-infected women to the intrauterine device (IUD) or hormonal contraception. Women randomized to hormonal contraception chose between oral contraceptive pills and DMPA. This analysis investigates the relationship between exposure to hormonal contraception and HIV disease progression [ defined as death, becoming eligible for antiretroviral therapy, or both]. Of the 595 women not on antiretroviral therapy at the time of randomization, 302 were allocated to hormonal contraception, of whom 190 (63%) initiated DMPA and 112 (37%) initiated oral contraceptive pills. Women starting IUD, oral contraceptive pills, or DMPA were similar at baseline. Compared with women using the IUD, the adjusted hazard of death was not significantly increased among women using oral contraceptive pills [1.24; 95% confidence interval (CI) 0.42-3.63] or DMPA (1.83; 95% CI 0.82-4.08). However, women using oral contraceptive pills (adjusted hazard ratio (AHR) 1.69; 95% CI 1.09-2.64) or DMPA (AHR 1.56; 95% CI 1.08-2.26) trended toward an increased likelihood of becoming eligible for antiretroviral therapy. Women exposed to oral contraceptive pills (AHR 1.67; 95% CI 1.10-2.51) and DMPA (AHR 1.62; 95% CI 1.16-2.28) also had an increased hazard of meeting this study’s composite disease progression outcome (death or becoming antiretroviral therapy eligible) than women using the IUD. In this secondary analysis, exposure to oral contraceptive pills or DMPA was associated with HIV disease progression among women not yet on antiretroviral therapy. This finding, if confirmed elsewhere, would have global implications and requires urgent further investigation.

Editors’ note: The relationship between hormonal contraception and disease progression was not an a priori hypothesis of this trial and 47% of the participants switched contraceptive methods, withdrew from the study, or were lost to follow-up. The researchers addressed the switching by treating contraceptive method as a time-varying exposure but the fact that women assigned to the contraceptive arm could choose either DMPA or oral contraceptives could have introduced confounding. Given that the risk of maternal mortality increases with each subsequent pregnancy, with a women’s lifetime risk of dying in pregnancy as high as one in 22 in sub-Saharan Africa, women need safe and effective contraception when they want it. These results are by no mean definitive but they support the urgent call for a trial evaluating the potential relationship between HIV disease progression and hormonal contraception.