July 8, 2016
This week, HIV experts argue for an HIV prevention cascade -- a counterpart to the established HIV treatment cascade -- with emphasis on treatment-as-prevention strategies. Another study finds that protease inhibitors may cause greater bone loss than other classes of HIV drugs. To beat HIV, you have to follow the science!
Global goals for reducing the number of people living with HIV can only be met if treatment-as-prevention strategies are combined with greater efforts to prevent people from being infected in the first place, write researchers from the U.S. and sub-Saharan Africa in a comment in The Lancet.
They argue a prevention cascade is an excellent tool for achieving higher rates of primary HIV prevention than are now common in southern and eastern Africa. Such an approach must address biomedical, behavioral and structural factors that may keep those at risk of acquiring HIV from consistently applying proven prevention techniques, such as voluntary medical male circumcision, condom use, early antiretroviral treatment, and pre-exposure prophylaxis.
Data from evidence-driven, outcome-oriented prevention programs also helps policymakers determine how to best allocate resources for the greatest benefit. Given the demographic shifts underway in many African countries, ambitious goals for reducing the burden of HIV can only be achieved if programs to prevent young people in those countries from acquiring HIV become much more rigorous, the authors warn.
The paper was published online in The Lancet.
The bone loss experienced by people living with HIV who take protease inhibitors (PIs) is greater on average than that of people taking combination antiretroviral regimens based on non-nucleoside reverse transcriptase inhibitors or nucleoside reverse transcriptase inhibitors, a recent review of relevant studies showed.
In a meta-analysis examined by this review, the odds ratio (OR) of experiencing osteoporosis was 1.57 for people taking PIs compared to those taking other classes of antiretrovirals. However, data from other studies reviewed suggested that the combination of PIs with tenofovir disoproxil fumarate (TDF, Viread) may be partly to blame for lower bone mineral density (BMD).
PIs directly affect bone cells and inhibit a person's vitamin D metabolism, which likely contributes to the BMD loss experienced by people who are taking a medication in this class, the study concluded. These effects exacerbate the BMD loss that people living with HIV experience during the first two years of any combination antiretroviral therapy.
The study was published online in Current Opinion in HIV and AIDS.
Impairing the interaction of HIV virions with endosomal sorting complexes required for transport (ESCRTs) -- machinery vital to many cellular processes within the body -- does not entirely stop the virions from growing out of the HIV-infected cells , but does cause a delay in that budding, according to a study published online in PLOS Pathogens.
In addition, activating the cells' release of protease during that delay causes the production of low- or non-infectious viral particles, further curbing the spread of HIV through the body.
Researchers used genetically engineered Gag proteins to interfere with two ESCRT proteins in human skin cells grown in a lab. Such interference delayed budding of the virus by 75 minutes and 10 hours, depending on the Gag protein used, and reduced the infectious power of the released viral particles by half or even turned them non-infectious.
The experiments further showed that the relatively large enzyme cargo carried by HIV requires more interaction with ESCRTs in order to release the virus from an infected cell than does a virus with a smaller cargo. The study shows that inhibiting ESCRTs is a promising approach for HIV drugs, according to its authors.
Barbara Jungwirth is a freelance writer and translator based in New York.
Follow Barbara on Twitter: @reliabletran.
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