• PERSISTENCE OF HIV DNA IN CEREBROSPINAL FLUID AND NEUROLOGICAL IMPLICATIONS

    Journal of Clinical Investigation, July 2019

    The persistence of HIV in sanctuary sites in the human body even in the presence of antiretroviral therapy (ART) is a potential barrier to HIV remission and cure. The central nervous system is one of those sanctuary sites and it has unique properties, in terms of cell composition and antiretroviral penetration. Because neurocognitive function can be compromised even in individuals whose HIV is well treated, it is important to understand HIV persistence in the nervous system. In the ACTG HIV Reservoirs Cohort Study (A5321), virally suppressed individuals with HIV taking long-term ART were tested for persistent HIV in their cerebrospinal fluid.

    https://www.jci.org/articles/view/127413

  • OPTIONS Study (A5241) Asks Whether NRTIs are Essential in Salvage Regimens

    Journal of Infectious Diseases, May 2019

    When people with HIV develop resistance to antiretroviral medications, their clinicians often prescribe previously used nucleoside reverse transcriptase inhibitors (NRTIs), along with other drugs, in the new “salvage” regimen, reasoning that the NRTIs may improve the chances of treatment response. These extra drugs may result in side effects, however, and it is not certain if they’re necessary if other active medicines are included in the salvage regimen. In the OPTIONS trial (ACTG A5241), the AIDS Clinical Trials Group asked whether NRTIs are an essential component of salvage regimens if the regimen has other active medications.

    https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiz281/5499329

  • DO ELITE CONTROLLERS REQUIRE ART FOR SECONDARY BENEFITS?

    Clinical Infectious Diseases, May 2019

    There is an ongoing debate in the literature about whether elite controllers require antiretroviral therapy (ART) for secondary benefits, including control for low-level viral replication and reduction of inflammation. ACTG A5308 attempted to resolve this debate by looking at the effect of ART on virologic suppression, the viral reservoir, immune activation, and quality of life in a group of elite controllers enrolled in the ACTG.

    https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz442/5498857?searchresult=1

  • Can Text Messaging Support Adherence for People Failing Secong-Line Therapy in Low- and Middle-Income Countries (MULTI-OCTAVE Study [A5288])

    Lancet Digital Health,  May 2019

    (ACTG) A5288 (MULTI-OCTAVE) is one of the first studies to look at interventions for medication adherence in lower-income and middle-income countries (LMICs) for individuals failing second line therapy. All participants in this unprecedented prospective interventional study were failing 2nd line ART, with the majority on lopinavir/ritonavir-based ART. Participants were either kept on that regimen or randomized to receiving third line ART regimens based on the results of viral genotyping on enrollment, and followed for a median of 72 weeks.

    https://www.thelancet.com/pdfs/journals/landig/PIIS2589-7500(19)30006-8.pdf

  • NWCS 399: CT as Non-Invasive Assessment of Fat Quality

    The Journal of Clinical Endocrinology & Metabolism, April 2019

    Fat quality or function contributes to risk for diseases such as heart disease, fatty liver disease, and diabetes, and may be as important as fat quantity when assessing the risk of poor health outcomes. In the past, fat quality could only be determined by performing fat biopsies and measuring fat cell size under the microscope. However, measuring fat cell density on a CT scan may also measure fat quality (lower density=poorer quality/more poorly functioning fat cells). NWCS 399 compared data from abdominal subcutaneous fat biopsy specimens, with fat density data from CT scans in the ACTG A5224s (a sub-study of A5202, which randomized adults living with HIV to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r)).

    Over 96 weeks of ART, fat quantity increased (+18%) and fat density decreased (-3%). Mean fat cell area correlated with fat density measured on CT scan both before and after ART and after adjusting for fat quantity, age, race, sex, CD4+ T lymphocyte count, and HIV-1 RNA. Therefore, subcutaneous fat density measured by CT scan served as an accurate representation of subcutaneous fat cell size in adults with HIV on and off ART, suggesting that CT is a useful tool for non-invasive assessment of fat quality.

    CT Fat Density Accurately Reflects Histologic Fat Quality in Adults With HIV On and Off Antiretroviral Therapy.

  • Underlying Factors Associated with Racial Disparities in HIV Outcomes

    February 1, 2019 Alexis Sexton Publications

    Open Forum Infectious Diseases, February 2019

    Racial/ethnic disparities in HIV outcomes have persisted despite effective antiretroviral therapy. The landmark ACTG A5257 study, examining initial non-NNRTI based regimens for ART, used clinical and socioeconomic data to assess factors associated with virologic failure and adverse events within racial/ethnic groups. Study authors analyzed data from 1762 participants: 757 self-reported as non-Hispanic black (NHB), 615 as non-Hispanic white (NHW), and 390 as Hispanic. The proportion with virologic failure was higher for NHB (22%) and Hispanic (17%) participants compared with NHWs (9%). Factors associated with virologic failure were poor adherence and higher baseline HIV RNA level. Prior clinical AIDS diagnosis was associated with virologic failure among NHBs only, and unstable housing and illicit drug use for NHWs only. Factors associated with adverse events were female sex in all groups and concurrent use of medications for comorbidities in NHB and Hispanic participants only. This important study shows that modifiable risk factors associated with virologic failure and tolerability of ART differ between racial groups, suggesting interventions to prolong the durability of first-line regimens.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372057/?report=reader

  • DTG/3TC is Durable Initial Therapy through 48 Weeks

    January 18, 2019 Alexis Sexton Publications

    Journal of Antimicrobial Chemotherapy, January 2019

    This study is an important subset analysis of the AIDS Clinical Trials Group study A5353, which demonstrated the efficacy and safety of dolutegravir and lamivudine for the initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA levels 1000-500 000 copies/mL for the first time. This study shows the durability of these findings out to 48 weeks and also compares the efficacy of the regimen in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL. Authors show that – in 120 enrolled eligible participants included in the analysis, 85% (95% CI 77%-91%) had virologic success at 48 weeks. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between those with starting HIV RNA levels below and above 100,000 copies/mL. No new drug resistance mutations were observed in any of the failures and the regimen was well-tolerated.  This study, along with the GEMINI study, verifies the durability of DTG/3TC as initial therapy out to 48 weeks for those who are naïve to HIV therapy and have no baseline resistance mutations.

    https://academic.oup.com/jac/article/74/5/1376/5296308?searchresult=1