Health care for women has been a challenge for thousands of years. It's even been a point of celebration as depicted in images of a woman giving birth in a barn, iconic of the holiday season.
But at the last IAS International AIDS Conference (AIDS 2018) there were no stars shining over Bethlehem in the Amsterdam horizon for tens of millions of HIV-positive women. Instead, studies at last year's AIDS 2018 show that women living with HIV are experiencing significant barriers to comprehensive treatment, statistical representation, and the retention in care needed to prevent and treat co-morbidities.
In fact, co-morbidities are increasingly becoming the most complex, expensive, and serious manifestations of HIV in the antiretroviral era.
In a thought-provoking presentation at AIDS 2018, David Malebranche MD, MPH, from Morehouse School of Medicine, demonstrated how the HIV continuum of care is failing key population often overlooked. A key point of Dr. Malebranche’s presentation was to stop solely blaming patients for difficulties existing in their maintaining consistent treatment and care, and examine how the biases of the medical community are contributing to these inconsistencies.
This failure is also driving single HIV-positive mothers living below the poverty line, who are experiencing co-morbidities relating to their HIV, to fall through the cracks of the current treatment paradigm. These women experience extreme difficulty getting into and staying retained in clinical studies and maintaining medical appointments. In many cases, this is due to clearly defined barriers: transportation, lack of childcare, conflicting schedules, and a lack of support from an economy allotting just enough to survive but not the dignity needed to surpass mere existence.
Continued lack of support for key populations of people living with HIV (PLWHA) and the unique obstacles they face, only hinder efforts to meet challenges to delivering treatment, particularly of HIV associated co-morbidities.
Data presented at AIDS 2018, as well as in peer reviewed literature, indicates HIV-positive single mothers living below the poverty line have a high incidence of long-term economic and personal challenges that are counterproductive to treatment. As a demographic, women and many of the diseases that affect them remain unrepresented in recent studies by The AIDS Clinical Trial Groups (ACTGs), ANRS, and other publicly sponsored research networks.
A recent study showed that HIV-positive women with chronic depressive symptoms are twice as likely to die, even after adjusting for mortality predictors such as CD4 count and age. Also identified was the importance of mental health issues on factors of co-morbidities like cardiovascular disease and co-infections.
Without HIV exposure, women show greater predisposition for CVD, IBD, and parasitic infections such as toxoplasmosis. Toxoplasmosis has been shown to facilitate the progression of HIV along with other diseases including CVD, as well as facilitate the permissiveness of co-morbidities. Taken together, these clinical concerns are undermining the premise of HIV being a chronic manageable condition in neglected key populations.
There’s a library of literature substantiating that women generally present high risk factors for developing cardiovascular disease, and unsurprisingly, CVD is the leading cause of mortality in HIV- positive women. HIV exacerbates inflammation and compounds traditional cardiovascular disease risk factors. HIV is associated with a 50 percent increased risk of AMI beyond that explained by recognized risk factors.
Additionally, drugs like Maryzime’s MB103 for AMI may offer a significant advancement in the treatment of HIV associated AMI. The success seen in the REPREIVE study, where Patavastatin showed benefit in the prevention and treatment of HIV-related CVD, show the need for more research on interventions such as MB103 to address the various forms of CVD in women, and all PLWHAs, are experiencing CVD.
Studies on ARV adherence and poly-pharmacy at AIDS 2018 demonstrated the absence of focus on clinical challenges HIV-positive single mothers experience in navigating the complexity of treatment landscapes. And while studies addressing drug resistance are plentiful, correlations of resistance and co-morbidities in HIV-positive single mothers, remain unaddressed.
A study published in the June online edition of the Journal of Acquired Immune Deficiency Syndromes examining poly-pharmacy in HIV-positive people, reported that half of people over 50 were at risk of drug interactions between ARVs and other medications.
Studies at the conference focused on Immune dysfunction due to elevated inflammation- which drives co-morbidities and contributes to cancers that disproportionately affect HIV- positive women -was sparse. We know seven out of 10 women develop an autoimmune disease such as Crohn’s and IBS — comorbidities that occur more frequently in the context of HIV.
We also know that low CD4 lymphocytes affect severity in both HIV and IBD. The incidence of ulcerative colitis in HIV is about double that of what is expected in a normal population. Use of several drugs for autoimmune diseases that affect women most, such as IBD and Crohn’s, are known to increase risk of lymphoma. Two of the leading drugs approved for such conditions, Remicade and Humira, are immune suppressive and a third, Entyvio, increases risk for Progressive Multifocal Leukoencephalopathy (PML).
Lodonal, a formulation of low-dose Naltrexone in phase IIB/III development by Immune Therapeutics, demonstrated significant improvements in symptom relief in Crohn’s, reduction of inflammation, and could be an option for these women and many conditions that disproportionately affect them.
HIV-related diarrhea was reported at AIDS 2018 to still be occurring at the same rate as it was 17 years ago. According to a poster presentation, a review of 38 ARV focused clinical trials found that the rate of non- infectious diarrhea has remained at 17-18 percent despite the widespread use of ARVs. Mytesi, the only FDA approved treatment for HIV-related diarrhea, continues to be under-prescribed. This troubling condition is linked to ARV non-adherence, malnutrition, depression and isolation conditions many HIV-positive women struggle with.
The AIDS 2018 and HIV Glasgow 2018 conferences demonstrated how far we’ve come over the course of the epidemic in advancements of ART and the HIV prevention toolbox.
Atreca published data on their BNAB immune capture platform showing exceptional activity directed against HIV from individuals with serum activity capable of potently neutralizing genetically diverse strains of HIV. So, while we’re waiting in the purgatory of balancing the marginal, incremental advances of small molecule antiretroviral drug development for therapeutic vaccines like the phase 2B Vacc-C5 from Bionor Pharma, early stage BNABS by Atreca, and with long acting ARV’s just on the horizon, that could transform the course of epidemic, poz patients continue to die from preventable co-morbidities driven by elevated inflammation.
The HIV pandemic is changing and the community needs to support prioritizing agendas at the ACTG’s, MHRP, and the CTN to address the emerging risks of GI co-morbidities like Crohn’s and IBS, HIV-related CVD manifestations of AMI and A-Fib. Not to mention, accelerated aging with HIV along with the concerns that co-infection with toxoplasmosis, HPV, and other pathogens represent to morbidity — not just for women and single HIV-positive mothers, but on a global scale.
AIDS 2018 should have been a turning point for a new scientific agenda that created room at the table for overlooked HIV key populations. The upcoming 2019 HIV Science Conference in Mexico City in July is our next best chance to make that priority a reality.