This is the first article to present population trends in HIV mortality across selected Latin American countries. Results suggest that six out of the eleven countries examined show a decline in HIV mortality after the initiation of national policies providing free public-sector access to ART. The analysis also illustrates how men and women are affected and vulnerable with regards to HIV: adult men had consistently higher mortality due to HIV while women showed less improvement in rates over time and lower mean age at death.
The shift in mean age at HIV death, as measured in our data, ranged from 2 to 8 years. Many factors, including changes during the study period in HIV incidence overall and among specific age groups, an increase in HIV incidence among older adults [41–43], increase in life expectancy among HIV patients, access to and quality of ART, and patients' perceptions of ART availability and effectiveness, are likely to have influenced mortality rates during the period examined by this analysis. Our finding that introduction of national policies for public ART provision coincided with an increase in the mean age of death from 2 to 8 years requires further investigation to better understand the underlying factors. Among many possible explanations, an increase in survival of HIV-infected patients may be related to improved access and quality of ART and in the management and prophylaxis of opportunistic infections, as previously demonstrated in several cohort studies [44–46].
Mortality rates in this study were calculated relative to the census population so that observed changes may capture not only improvements in ART but also changes in epidemic dynamics. For example, decreasing HIV incidence with all other factors stable could, in theory, lead to mortality declines. However, estimated HIV cases and ART treatment caseloads increased, rather than decreased, in all countries included in this analysis during the period [13, 47]. Similarly, an increase in the age distribution of incident cases could theoretically explain the increase in age of death observed in this study. Yet, this is unlikely to be the case as younger individuals continue to comprise the majority of reported HIV and AIDS cases .
The consistently elevated levels of mortality among men compared to women is most likely explained by the fact that men who have sex with men (MSM) continue to be one of the populations with the highest prevalence throughout Latin America ; and may also reflect prevalent gender norms, socioeconomic roles and structures that translate to gender inequities in access to timely diagnosis and treatment in Latin America, including homophobia and machismo [49, 50].
Differentials in access to HIV services between men and women could contribute to differences in mortality, however the direction of this effect is unclear. Some studies in Latin America have found that women tend to start ART with higher CD4 counts than men, which could be attributed to the scale-up of HIV screening in pregnant women as an entry point to HIV care and treatment. This delay in the HIV detection in the male group could partially explain a higher HIV related mortality. On the other hand, socioeconomic disparities may affect women's ability to access adequate HIV treatments and services more than men both in the US and LA [51–53]. Our findings concurred with these previous publications.
The reduction in HIV mortality rates in the population appears remarkable. This begs the question of how, and how much, HIV mortality could be reduced further? In the United States, the age-adjusted HIV death rate fell by 28% from 1995 to 1996, by 46% from 1996 to 1997, and by 18% from 1997 to 1998. After 1998, the rate leveled off at around 5 per 100,000, which is similar to the level reported in Brazil, Argentina and Costa Rica for the same period [54, 55]. Other factors also affect HIV mortality such as the unrelenting occurrence of new infections, lagging ART coverage in some areas, late presentation for HIV care with delayed ART uptake, suboptimal treatment and adherence and lack of treatment options . Specific age, sex and gender identity subgroups may still be experiencing higher HIV mortality even within countries that have substantially lowered their rates. At the regional level this information is not available to conduct more in-depth analysis. National institutions, particularly those where mortality has remained stable or increased, should engage in operational research to identify lost opportunities in the response effort and address inequities in services' access that further reduce HIV mortality.
ART coverage and rate of scale-up, which were not captured in the models, differed among countries and were likely to influence HIV mortality trends. ART coverage may have been too low in some countries to reduce HIV mortality levels. This may be the case in Ecuador where ART scale-up was limited until 2006, when international funds became available [57, 58].
Moreover, the rise in HIV mortality seen in some countries may have resulted from a gap in primary and secondary prevention and including late HIV testing and diagnosis, low adherence and issues in treatment quality despite relatively high ART coverage [13, 16, 46].
An effective universal ART coverage is one goal for controlling the HIV/AIDS epidemic. The introduction of policies that make the access of ART universal and free are key to fulfill this goal, but in reality their coverage varied greatly among the different countries. Furthermore, there are countries with low coverage and this issue could explain the mortality trends differences found in the study.
The principal limitations of the study are associated with the source and quality of the data. Errors in registered mortality could occur during data reporting collection and processing as well as by limitations in medical knowledge, diagnostic errors and deficiencies in the death certification. The validity of the distribution by cause is also affected by under reporting of deaths and cause of death certification, even when conducted by physicians. In many Latin American countries, registration of death is not performed by physicians, particularly in remote and rural areas, which can compromise the accuracy of cause of death classification. Physicians may also prefer certain kinds of diagnoses, introducing biases that may vary from country to country and over time . In addition, legal and societal concerns may lead to the underreporting of causes of a sensitive nature, such as HIV, on the death certificate . Another limitation of the study is the difference in the time of follow up after public ART introduction. Some like Brazil had 11 years of follow up while others, like El Salvador, had only 2 years of follow up post public ART provision.
We also expect some degree of bias due to variation in correct HIV diagnosis and cause of death registration over time. Tendencies to misclassify as well as intentionally replace the registered cause of death may change over time. For example, opportunistic infections and cancers may be more frequently recorded as cause of death in lieu of HIV [7, 60–62]. The degree, to which such effects occur, however, is unclear and should be examined further.