HIV This Week

Maternal mortality for 181 countries, 1980-2008: a systematic analysis of progress towards Millennium Development Goal 5.

Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, Makela SM, Lopez AD, Lozano R, Murray CJ. Lancet. 2010; April [Epub ahead of print].

Maternal mortality remains a major challenge to health systems worldwide. Reliable information about the rates and trends in maternal mortality is essential for resource mobilisation, and for planning and assessment of progress towards Millennium Development Goal 5 (MDG 5), the target for which is a 75% reduction in the maternal mortality ratio (MMR) from 1990 to 2015. The authors assessed levels and trends in maternal mortality for 181 countries. They constructed a database of 2651 observations of maternal mortality for 181 countries for 1980-2008, from vital registration data, censuses, surveys, and verbal autopsy studies. They used robust analytical methods to generate estimates of maternal deaths and the maternal mortality ratio for each year between 1980 and 2008. They explored the sensitivity of their data to model specification and show the out-of-sample predictive validity of their methods. They estimated that there were 342 900 (uncertainty interval 302 100-394 300) maternal deaths worldwide in 2008, down from 526 300 (446 400-629 600) in 1980. The global maternal mortality ratio decreased from 422 (358-505) in 1980 to 320 (272-388) in 1990, and was 251 (221-289) per 100 000 live births in 2008. The yearly rate of decline of the global maternal mortality ratio since 1990 was 1.3% (1.0-1.5). During 1990-2008, rates of yearly decline in the maternal mortality ratio varied between countries, from 8.8% (8.7-14.1) in the Maldives to an increase of 5.5% (5.2-5.6) in Zimbabwe. More than 50% of all maternal deaths were in only six countries in 2008 (India, Nigeria, Pakistan, Afghanistan, Ethiopia, and the Democratic Republic of the Congo). In the absence of HIV, there would have been 281 500 (243 900-327 900) maternal deaths worldwide in 2008. Substantial, albeit varied, progress has been made towards MDG 5. Although only 23 countries are on track to achieve a 75% decrease in maternal mortality ratio by 2015, countries such as Egypt, China, Ecuador, and Bolivia have been achieving accelerated progress.

For full text access click here:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60518-1/fulltext

Editors’ Note: Both early maternal mortality defined as the death of women during pregnancy, childbirth, or in the 42 days after delivery, and late maternal mortality in the period from 43 days to 1 year post-delivery are notoriously difficult to measure accurately. This study drew on every available data source, tried to correct for misclassification, and ran predictive validity tests on their modelling approach. Late maternal mortality and mortality due to Incidental causes such as motor vehicle accidents, drowning, etc. are not included in the calculation of the maternal mortality ratio (MMR). Thus the MMR includes early maternal deaths due to direct obstetric causes, indirect causes (aggravated by pregnancy), and HIV infection causes, and is calculated as the number of maternal deaths per 100,000 live births. The target for Millennium Development Goal (MDG) 5 is a 75% reduction in the MMR between 1990 and 2015 which would require a 5.5% annual decline in the MMR when it has fallen 1.8% per year from 1980 to 2008. We need to speed up the decline to get on target. This stocktaking analysis has striking findings. Analysis of the 1.5% annual rate of decline in the number of maternal deaths from 1980 to 2008 reveals a disturbing trend. The decline was 1.8% annually between 1980 and 1990, dropping to 1.4% from 1990 to 2008. In fact, had there been no HIV epidemic, the decline overall would have been 2.2% per year, not 1.5%. With the proportion of global maternal deaths occurring in sub-Saharan Africa having increased from 23% in 1990 to 52% in 2008, as the HIV epidemic in the region deepened, it is clear that initiating antiretroviral therapy for pregnant women with HIV infection worldwide, but particularly in sub-Saharan Africa, could help get us on track. At the same time, we need to continue to address factors that influence maternal mortality and HIV such as education for girls - it rose from 1.5 years in 1980 to 4.4 years in 2008 in sub-Saharan Africa. Continued reductions in the total fertility rate, which fell from 3.7 in 1980 to 2.6 in 2008, acceleration in the slow increases in the coverage of skilled birth attendance, and specific tracking of HIV-related maternal mortality are top priorities. Preventing HIV infection in women, preventing unintended pregnancy in women who have HIV infection, and putting pregnant women with HIV infection on antiretroviral therapy for their own health would have rapid and sustained effects on maternal mortality in high HIV prevalence settings.

Treatment with antiretroviral therapy is not associated with increased sexual risk behaviour in Kenyan female sex workers.

McClelland RS, Graham SM, Richardson BA, Peshu N, Masese LN, Wanje GH, Mandaliya KN, Kurth AE, Jaoko W, Ndinya-Achola JO. AIDS. 2010; 24:891-7.

The objective of this study was to test the hypothesis that sexual risk behaviour would increase following initiation of antiretroviral therapy. A prospective cohort of Kenyan female sex workers were recruited in Mombasa, Kenya between 1993-2008. Eight hundred and ninety-eight women contributed HIV-1-seropositive follow-up visits, of whom 129 initiated antiretroviral therapy. Beginning in March 2004, antiretroviral therapy was provided to women qualifying for treatment according to Kenyan National Guidelines. Participants received sexual risk reduction education and free condoms at every visit. Main outcome measures included unprotected intercourse, abstinence, 100% condom use, number of sexual partners, and frequency of sex. Outcomes were evaluated at monthly follow-up visits using a 1-week recall interval. Compared with non-antiretroviral therapy-exposed follow-up, visits following antiretroviral therapy initiation were not associated with an increase in unprotected sex [adjusted odds ratio (AOR) 0.86, 95% confidence interval (CI) 0.62-1.19, P = 0.4]. There was a nonsignificant decrease in abstinence (AOR 0.81, 95% CI 0.65-1.01, P = 0.07), which was offset by a substantial increase in 100% condom use (AOR 1.54, 95% CI 1.07-2.20, P = 0.02). Numbers of sex partners and frequency of sex were similar before versus after starting antiretroviral therapy. A trend for decreased sexually transmitted infections following antiretroviral therapy initiation provides additional support for the validity of the self-reported behavioural outcomes (AOR 0.67, 95% CI 0.44-1.02, P = 0.06).  In the setting of ongoing risk reduction education and provision of free condoms, initiation of antiretroviral therapy was not associated with increased sexual risk behaviour in this cohort of Kenyan female sex workers.

For abstract access click here:

http://www.ncbi.nlm.nih.gov/pubmed/20179576

Editors’ note: This finding of no risk enhancement/risk compensation behaviour in these Nairobi sex workers after they started on antiretroviral treatment stands on firm ground. In fact, a highly significant increase of more than 50% in consistent condom use was reported. This prospective study collected considerable amounts of data on sexual behaviour before antiretroviral therapy was initiated, followed women for a median of more than 2 years after treatment started, had similar intensity risk-reduction counselling before and after treatment began, and was large enough to control for multiple potential confounding factors. As well, biological indicators such as the presence of sperm in genital secretions indicating recent unprotected sexual intercourse and incident sexually transmitted infections suggesting inconsistent condom use helped validate self-reports of sexual behaviour. There has been concern that the benefits of treatment scale-up in decreasing viral loads and reducing HIV transmission might be shot out of the water by increased sexual risk taking as people feel better but this study of Nairobi sex workers confirms findings from the majority of African studies demonstrating no increase in risk behaviour when people start on antiretroviral therapy.

Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults.

Siegfried N, Uthman OA, Rutherford GW. Cochrane Database Syst Rev. 2010;3:CD008272

According to consensus, initiation of therapy is best based on CD4 cell count, a marker of immune status, rather than on viral load, a marker of virologic replication. For patients with advanced symptoms, treatment should be started regardless of CD4 count. However, the point during the course of HIV infection at which antiretroviral therapy is best initiated in asymptomatic patients remains unclear. Guidelines issued by various agencies provide different initiation recommendations according to resource availability. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing the initiation of antiretroviral therapy is clearly complex and must, therefore, be balanced between individual and broader public health needs. The objective of the study was to assess the evidence for the optimal time to initiate antiretroviral therapy in treatment-naive, asymptomatic, HIV-infected adults. The authors formulated a comprehensive and exhaustive search strategy in an attempt to identify all relevant studies regardless of language or publication status (published,unpublished, in press, and in progress). In August 2009, they searched the following electronic journal and trial databases: MEDLINE, EMBASE, and CENTRAL. They also searched the electronic conference database of NLM Gateway, individual conference proceedings and prospective trials registers. They contacted researchers and relevant organizations and checked reference lists of all included studies. Randomized controlled trials that compared the effect of antiretroviral therapy consisting of three drugs initiated early in the disease at high CD4 counts as defined by the trial were selected. Early initiation could be at levels of 201-350, 351-500, or >500 cells/microL, with the comparison group initiating antiretroviral therapy at CD4 counts below 200 x 10(6) cells/microL or as defined by the trial. Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Where clinically meaningful to do so, they meta-analysed dichotomous outcomes using the relative risk (RR) and report the 95% confidence intervals (95% CIs).  They found that one completed trial (N = 816) and one sub-group (N = 249) of a larger trial met inclusion criteria. They combined the mortality data for both trials comparing initiating antiretroviral therapy at CD4 levels at 350 cells/microL or between 200 and 350 cells/microL with deferring initiation of antiretroviral therapy to CD4 levels of 250 cells/microL or 200 cells/microL. There was a statistically significant reduction in death when starting antiretroviral therapy at higher CD4 counts. Risk of death was reduced by 74% (RR = 0.26; 95% CI: 0.11, 0.62; P = 0.002). Risk of tuberculosis was reduced by 50% in the groups starting antiretroviral therapy early; this was not statistically significant, with the reduction as much as 74% or an increased risk of up to 12% (RR = 0.54; 95% CI:0.26, 1.12; P = 0.01). Starting antiretroviral therapy at enrolment (when participants had CD4 counts of 350 cells/microL) rather than deferring to starting at a CD4 count of 250 cells/microL reduced the risk of disease progression by 70%; this was not statistically significant, with the reduction in risk as much as 97% or an increased risk of up to 185% (RR = 0.30; 95% CI: 0.03, 2.85; P = 0.29).One randomised controlled clinical trial found no statistically significant difference in the number of independent Grade  3 or 4 adverse events occurring in the early and standard antiretroviral therapy groups when the authors conducted an intention-to-treat analysis (RR = 1.72; 95% CI: 0.98, 3.03; P = .06). However, when analyzing only participants who actually commenced antiretroviral therapy in the deferred group (n = 160), the trial authors report a statistically significant increase in the incidence of zidovudine-related anaemia (8.1%) compared with those in the early initiation group (3.4%) (RR = 0.42; 95% CI: 0.20, 0.88; P = 0.02). The authors conclude that there is evidence of moderate quality that initiating antiretroviral therapy at CD4 levels higher than 200 or 250 cells/microL reduces mortality rates in asymptomatic, antiretroviral therapy-naive, HIV-infected people. Practitioners and policy-makers may consider initiating antiretroviral therapy at levels </= 350 cells/microL for patients who present to health services and are diagnosed with HIV early in the infection.

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Editors’ note: Why do people say that there is equipoise (meaning that we really don’t know which way the answer will go) for the trials that are currently underway to determine whether it is beneficial to start antiretroviral treatment at even higher CD4 counts than the 350 cells/µl currently recommended by WHO? It is because the two small trials described here only looked at CD4 counts under 350 cells/µl. Pooled data from the Haiti study (816 people) and the antiretroviral treatment naive sub-sample from the SMART study (248 people) found that starting antiretroviral treatment between 200-250 and 350 CD4+ cells/µl compared with under 200 cells/µl reduces mortality in treatment-naïve people living with HIV who have no symptoms. A small proof of concept trial http://clinicaltrials.gov/ct2/show/NCT00491556 is recruiting 100 people aged 18-24 to start treatment above 350 cells or wait until their CD4 counts fall below 350 cells while a large trial, Strategic Timing of Antiretroviral Treatment (START) http://clinicaltrials.gov/ct2/show/NCT00867048, is  enrolling 4000 antiretroviral-naive people with CD4 counts greater than 500 cells/µl at 87 sites in 23 countries. Participants will be randomized to start antiretroviral treatment immediately or wait until their first CD4 count of less than 350 cells/µl or clinical signs of AIDS. At issue is whether adherence challenges, long-term side-effects, chances of developing other illnesses, resistance to HIV medicines, frequency of doctor visits, and cost of medical care associated with early antiretroviral treatment are outweighed by reduced risk of HIV disease progression conferred by these medicines. The bottom line for most people is which strategy improves general health, quality of life, and satisfaction.

Changes in sexual behaviours: from secular trends to public health policies.

Bajos N, Bozon M, Beltzer N, Laborde C, Andro A, Ferrand M, Goulet V, Laporte A, Le Van C, Leridon H, Levinson S, Razafindratsima N, Toulemon L, Warszawski J, Wellings K. AIDS. 2010; 24:1185-91.

The objective of the study was to explore the relative contribution of secular trends and public health policies to changes in sexual behaviour. Three random probability surveys of the sexual behaviour of people aged 18-69 years were conducted in 1970, 1992 and 2006 in France. Data of the 2006 survey (n = 12 364) were compared with those from two surveys carried out in 1970 (n = 2625) and 1992(n = 20 055). Over the last decades, median age at first intercourse has decreased by 4 years for women (22.0 in the 1930s vs. 17.6 in the 2000s) and 1 year for men (18.1 vs. 17.2). Lifetime number of sexual partners increased for women (1.8 in 1970 vs. 4.4 in 2006), but not for men (11.8 vs. 11.6). At the same time, the proportion of respondents, especially women, who reported nonpenetrative sexual practices and considered sexual intercourse essential to well being was on the increase. These changes are mainly attributed to an increase in women's social status. A marked increase in condom use was observed following the first HIV prevention campaigns in the 1980s. Public health interventions that are synergistic with trends in social norms are likely to be more effective than those that run counter to them. In France, sexual health and HIV prevention policies aimed at harm limitation appear to have chimed with secular trends. The evidence of greater diversification of sexual practices offers potential to increase the range of safer sex messages used in public health interventions.

For abstract access click here:

http://www.ncbi.nlm.nih.gov/pubmed/20299962

Editors’ note: This fascinating retrospective analysis of trends in sexual behaviours in France over almost three quarters of a century reveals dramatic changes, particularly among women. The gap between age at first sex between men and women has fallen from 4 years to 4 months while use of any contraceptive method rose steadily from 37% in the early 1940s to 92.9% by 2005. Lifetime numbers of sexual partners remained stable for men of all ages but increased for women from 1.8 in 1970 to 4.4 in 2006. Condom use at first sex was below 10% for those starting sex before 1960 but rose to more than 80% by the mid-1990s. Although it is difficult to sort out whether changes in sexual behaviour were the result of public health interventions or the result of changes in the broader social context, the fact that condom use at first sex became normalised was likely the result of a focus on the routinization of condom use in HIV public education campaigns. From the HIV perspective, the findings about increasing nonpenetrative sexual practices are striking: lifetime reported masturbation increased three-fold for women aged 20-49 years from 19% in 1970 to 62% in 2006 and for men from 71% to 92%. Lifetime experience of oral sex increased from 51% to 91% for women and 55% to 94% for men. This suggests that the UNAIDS term ‘abstinence from penetrative sex’ as an HIV prevention strategy could have public health significance equivalent to condom promotion among young people in some settings.