Current HIV/AIDS Reports

Highly active antiretroviral therapy (HAART) has signi ficantly improved the prognosis of patients with HIV infection; however, the use of protease inhibitors has been associated with increased cardiovascular events and worsening of multiple coronary heart disease risk factors including dyslipidemia, insulin resistance, and endothelial dysfunction. Endothelial dysfunction may be caused by the infection itself, the immunologic responses due to the HIV virus, and also by the effects of HAART through their effects on both lipid and glucose metabolism. The study of endothelial function in HIV infection and its modifications by HAART is an exciting new field in clinical research, limited by multiple factors such as viral factors, immunologic conditions, and metabolic drug effects that could affect the interpretation of endothelial impairment. Further studies are still needed to understand the significance of endothelial dysfunction in the cardiovascular risk assessment of patients with HIV infection.

While antiretroviral therapy (ART) has had a tremendous impact on the morbidity and mortality of patients with HIV, there is evidence that many HIV-infected women experience treatment challenges that are different from men and these challenges are often associated with poorer outcomes. In the United States, blacks and Latino women are disproportionately affected by the HIV epidemic related to lack of access to high-quality HIV care, and socioeconomic factors. In Africa and Asia, HIV infection in women is affected by gender norms that often leave women dependent upon men (either emotionally or financially) and vulnerable in relationships. These gender norms and, in some cases, fears of violence make it difficult for women to refuse unprotected sex, and can contribute to higher infection rates in women and delayed entry to care. Many African migrants in Europe and Australia may feel stigmatized and fear discrimination when accessing care. As a consequence, despite the availability of highly active antiretroviral therapy, women with HIV often have delayed entry into care and experience poor outcomes. With the notable exception of treatment during pregnancy, there is little in the published literature to suggest that the treatment of choice for treatment-naïve patients should be determined by the patient’s sex. While virologic efficacy of ART may be similar in large clinical trials, differences in the frequency of treatment-related side effects and the impact of pregnancy and/or child-bearing status on treatment choice is well documented. In this paper we aim to discuss antiretroviral therapy in HIV-infected women, the sex-specific barriers to starting care, the differences in outcomes, and complications.

Highly active antiretroviral therapy (HAART) delays clinical progression by suppressing viral replication, measured by a substantial reduction in HIV RNA, allowing the immune system to reconstitute, measured in most studies by an increase in CD4 cells. These virologic and immunologic consequences do not occur uniformly among HAART users. Markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while receiving HAART. In this report, we review studies describing the heterogeneous virologic and immunologic progression after the initiation of HAART, discuss methodologic concerns in the study of the response of biomarkers, and update findings obtained in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of antiretroviral therapy, and age at the time of initiation are independent determinants of response.

This review focuses on the cerebrospinal fluid (CSF) findings in connection to the central nervous system (CNS) reservoir in treatment-naïve and virally suppressed PLWH, followed by the findings in CSF HIV-1 escape and analytical treatment interruption studies. Compared to chronic infection, initiating antiretroviral therapy (ART) during acute HIV-1 infection results in more homogeneous longitudinal benefits in the CNS. Viral variants in CSF HIV-1 escape are independently linked to infected cells from the systemic reservoir and in the CNS, highlighting the phenomenon as a consequence of different mechanisms. HIV-infected cells persist in CSF in nearly half of the individuals on stable ART and are associated with worse neurocognitive performance. Future studies should probe into the origin of the HIV-infected cells in the CSF. Examining the capacity for viral replication would provide new insight into the CNS reservoir and identify strategies to eradicate it or compensate for the insufficiency of ART.

Protease inhibitor monotherapy has been shown to be effective in maintaining long-term viral suppression in a majority of patients. Withdrawal of nucleoside analogues can prevent long-term toxicity related to these drugs. Clinical trials have recently reported preliminary data on the beneficial effect of protease inhibitor monotherapy on body fat distribution and bone metabolism. Some of the uncertainties possibly associated with protease inhibitor monotherapy such as the increased risk of neurological events and a higher level of subclinical inflammation will be discussed in this review.

This review points out unmet medical needs and open research questions of older adults living with HIV. Starting from the definition of aging in HIV, it explores the mosaic of this condition at epidemiological, pathophysiological, and clinical level. Antiretroviral management and diverse models of care are critically discussed. Aging cohorts suggest HIV as a paradigm of chronic inflammation and immune activation with specific aging trajectory patterns in which antiretroviral therapy may play a role. In the absence of randomized clinical trials, observational cohorts show that therapy is driven by duration of HIV infection and burden of non-infectious comorbidities. This review suggests that geriatric approach should be used to recognize the complexity of aging goes beyond the viro-immunological success and management of progressive accumulation of non-communicable diseases. This requires recognition of frailty and geriatric syndromes to stratify patients’ diversity by using comprehensive geriatric assessment tools.