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CROI 2015: Levonorgestrel Contraception May Be Less Effective for Women Taking Efavirenz

African women who took efavirenz as part of a combination antiretroviral regimen were more likely to become pregnant while using the levonorgestrel implant, likely due to a drug interaction that lowers levels of the hormonal contraceptive, according to a presentation at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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Trial of CCR5-Deleted Stem Cell Gene Therapy for HIV Gets FDA Go-Ahead

The U.S. Food and Drug Administration (FDA) has given approval to proceed with a clinical trial of a gene therapy method that cuts the gene for the CCR5 coreceptor out of stem cells, making them resistant to HIV entry, the California Institute for Regenerative Medicine (CIRM) recently announced.

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CROI 2015: Cabotegravir and Rilpivirine Effective for HIV Maintenance Therapy at 96 Weeks

A combination of 2 once-daily oral antiretrovirals -- the next-generation integrase inhibitor cabotegravir (GSK1265744) and the approved NNRTI rilpivirine -- was as effective as an efavirenz-based regimen when used as maintenance therapy to keep viral load suppressed, according to a poster presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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Valacyclovir May Reduce HIV Viral Load Even in People Without Herpes

The antiviral drug valacyclovir (Valtrex and generics), used to treat herpes simplex virus type 2 (HSV), led to a decrease in HIV viral load even among individuals who did not have genital herpes, according to a small study reported in the March 3 advance edition of Clinical Infectious Diseases.

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CROI 2015: Does HIV Make You Fat? Study Connects Viral Load with Fat Gains

HIV infection or inflammatory changes associated with it may be responsible for fat accumulation and body fat redistribution, rather than antiretroviral drugs, according to a study presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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[Produced in collaboration with Aidsmap]

Grace McComsey of Case Western University in Cleveland said that although the association of subcutaneous fat loss (lipoatrophy) with mitochondrial damage caused by certain HIV drugs is well-established -- and most of the world no longer uses the drugs like stavudine (d4T) that are most strongly associated with it -- 2 decades of research had failed to establish a cause for the distinctive fat gain(lipohypertrophy), especially in the trunk and within the abdomen, seen in some people with HIV on antiretroviral therapy (ART).

Initially these fat gains were associated with protease inhibitors (PIs) but switching from PIs to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or to integrase inhibitors did not reverse fat gains. One study found greater fat gain in people taking boosted atazanavir (Reyataz) rather than efavirenz (Sustiva), but a general association with any drug or class of drugs had not been demonstrated. Given that untreated HIV infection usually results in weight loss, fat gains when people started ART, once it became available, may have understandably been associated with treatment rather than HIV.

The study McComsey presented, ACTG A5260s, compared changes in limb fat, trunk fat, visceral adipose tissue (central abdominal fat), and lean muscle mass in 1809 ART-naive patients starting either of the 2 boosted PIs atazanavir or darunavir (Prezista), or the integrase inhibitor raltegravir (Isentress), all combined with tenofovir/emtricitabine (Truvada).

DEXA and CAT scans measured fat and muscle distribution at baseline and nearly 2 years (96 weeks) later. They were then assessed for associations with drug regimen, baseline HIV viral load, Framingham risk score (a measure of the likelihood of cardiovascular disease), and a number of hormones, cytokines (cell messenger chemicals), and markers of inflammation: leptin (higher in obese people), adiponectin (lower in obese people), D-dimer (a coagulation marker), C-reactive protein (an inflammation indicator), and the cytokines or cytokine receptors interleukin 6 (IL-6), CD14, and CD163.

In terms of demographics, the study participants' average age was 36, 90% were men, and 44% were white (slightly more taking atazanavir). Their average pre-ART viral load was 34,150 copies/mL and their average CD4 count was 351 cells/mm3.  Those taking atazanavir had slightly, but not significantly, more limb and trunk fat, but not more visceral fat or muscle.

Limb, trunk, and visceral fat all increased during the 96 weeks on ART. Limb fat increased by 15% (20% on raltegravir), trunk fat by 22% (16% on atazanavir and 29% on raltegravir), and visceral fat by 31%; the differences between drugs were not statistically significant. Lean muscle mass increased slightly, by 2%, in people on atazanavir or raltegravir, and by 1.2% in patients taking darunavir; this was a significant difference but probably does not reflect any real difference between the drugs.

Increases in visceral fat were associated with lower leptin and higher adiponectin levels, but this probably is effect rather than cause, as adiponectin is secreted by fatty tissue. Subcutaneous limb fat gain was also associated with higher IL-6 and lean body mass gain with higher D-dimer and lower baseline CD4 -- the latter not unexpected, as lean body mass falls with AIDS.

However by far the strongest association with fat gain was with high viral load. There were mean increases of at least 25% and up to 35% in both subcutaneous and visceral fat in people who had a baseline viral load over 100,000 copies/mL, whichever drug they were taking. In patients with a baseline viral load below 100,000 copies/mL, the fat gains were below 10%, apart from a gain in visceral fat of about 14% in people taking raltegravir. She noted that even when adjusted for inflammatory markers, HIV viral load was still significantly associated with fat gain.

McComsey said that the fat gains observed were not necessarily those associated with health improvement due to control of HIV. "A 30% gain in visceral adipose tissue in just 2 years is pretty bad," she said. "Even limb fat increased by 1.5 kilos from a baseline of 7 kilos (21%). There was an average increase in 3.0 to 3.5 in people’s BMI [body mass index] score." Although people in general may be getting fatter, it does not happen as fast as this, she added.

3/17/15

Reference

GA McComsey, C Moser, JS Currier, et al. Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 140.

CROI 2015: Experimental Agents Reverse HIV Latency, Help Immune System Fight Infected Cells

Researchers at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle presented data on several experimental agents that may play a role in achieving a "functional cure" for HIV, or prolonged remission without disease progression. These include drugs that reactivate the latent HIV reservoir, interfere with expression of viral DNA, and help the immune system target HIV-infected cells.

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CROI 2015: Circumcision is Reducing HIV Incidence in Uganda, Rakai Community Study Shows

The growing uptake of medical male circumcision by men in the Rakai district of Uganda is leading to a substantial reduction in HIV incidence among men in one of the districts worst affected by HIV, Xiangrong Kong of Johns Hopkins Bloomberg School of Public Health reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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Today Is National Native HIV/AIDS Awareness Day

March 20 marks the 9th annual observation of National Native HIV/AIDS Awareness Day (NNHAAD), an occasion to highlight the impact of HIV and AIDS on American Indian, Alaska Native, and Native Hawaiian communities.

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CROI 2015: We May Need to Combine Many Approaches to Achieve a Cure for HIV

It is unlikely that one single approach will achieve a cure for HIV infection, according to research presenting at a community cure workshop held the day before the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: Stopping Co-trimoxazole During ART Raises Risk of Bacterial Illness and Malaria

Stopping trimethoprim/sulfamethoxazole (Co-trimoxazole) prophylaxis increases the risk of serious bacterial infections and malaria, even at high CD4 cell counts, among people with HIV taking antiretroviral therapy (ART) in Uganda, according to results of a randomized trial presented by Jonathan Levin of the UK Medical Research Council at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: Financial Incentives Did Not Improve Linkage to Care or HIV Viral Suppression

A U.S. study that offered patients gift cards to present for HIV care after testing, and also to stay in care and maintain an undetectable viral load, did not succeed in its main aims and with most patients. Rates of linkage to care, retention in care, and viral suppression were not significantly higher in centers where patients received gift cards than in ones where they did not, according to research presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. However, the study did produce some improvement in the proportion of people who remained in care. And it improved viral suppression rates in smaller and under-performing centers.

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Study Suggests HIV May Be Less Infectious than Assumed During Early Infection

The likelihood of HIV transmission during the acute phase of HIV infection may not be as high as previously estimated based on data from a retrospective cohort study in Rakai, Uganda, according to an analysis published in the March 17 edition of PLoS Medicine. If confirmed, these findings suggests that antiretroviral treatment as prevention (TasP) may be even more effective, as it would not be compromised as much by transmission occurring before partners with HIV are diagnosed and start therapy.

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CROI 2015: Breastfeeding Mothers with HIV Often Undiagnosed in Sub-Saharan Africa

A large proportion of women in sub-Saharan Africa who are at high risk of transmitting HIV to their infants during breastfeeding are likely to be undiagnosed, if results of a large 3-country survey are applicable to other countries with a high prevalence of HIV among pregnant women, according to a study presented by David Maman of Médecins sans Frontières at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. The study also found very high rates of HIV incidence among pregnant women aged 15-29 in Kenya and South Africa, emphasizing the need for repeat testing during pregnancy and the breastfeeding period.

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CROI 2015: Does Emtricitabine Work Better than Lamivudine in Combination ART?

People with HIV who started an antiretroviral regimen containing emtricitabine (FTC; Emtriva) and NNRTIs were about half as likely to experience virological treatment failure as those who used the similar drug lamivudine (3TC; Epivir), according to an analysis of more than 6000 participants in the Dutch ATHENA cohort presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. No significant differences between emtricitabine and lamivudine were seen with boosted protease inhibitor regimens.

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CROI 2015: Inflammation and Gut Damage Persist in People with HIV Despite Early ART

Inflammatory changes and damage to the gut begin very soon after initial HIV infection, and may not return to normal even when people start antiretroviral therapy (ART) very early, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Biomarkers of inflammation, coagulation and fibrosis increased early on, and while they generally decreased after starting ART, they did not fall to levels seen in HIV-negative people.

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CROI 2015: Researchers Discuss HIV Cure Strategies

Researchers at the recent 2015 Conference on Retroviruses and Opportunistic Infections in Seattle discussed a variety of approaches to achieve a functional cure, or prolonged remission of HIV. Most experts expect that a combination of multiple approaches will be needed.

Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Experimental Agents Reverse HIV Latency, Help Immune System Fight Infected Cells

We May Need to Combine Many Approaches to Achieve a Cure for HIV

3/20/15

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CROI 2015: Tenofovir, Atazanavir & Lopinavir Associated with Raised Risk of Chronic Kidney Disease

Three antiretroviral drugs are associated with a slowly increasing rate of chronic kidney disease over time, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Although the risk of developing chronic kidney disease was low for people with normal kidney function -- with fewer than 1% of patients in the large D:A:D cohort developing it -- the use of any of these drugs was associated with 2 to 3 times higher risk of kidney disease developing over the course of 5 years on the drug.

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CROI 2015: Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Starting antiretroviral therapy (ART) very soon after infection may limit the size of the HIV reservoir and delay viral rebound after treatment interruption, according to several presentations at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Other research showed that various biomarkers may predict who will experience HIV rebound after stopping ART.

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CROI 2015: PEPFAR Abstinence and Faithfulness Funding Had No Impact on Sexual Behavior in Africa

Nearly $1.3 billion spent on U.S.-funded programs to promote abstinence and faithfulness had no significant impact on sexual behavior in 14 countries in sub-Saharan Africa, an analysis of sexual behavior data has shown. The preliminary findings were presented by Nathan Lo of Stanford University School of Medicine at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: FRAX Fracture Prediction Tool Underestimates Fracture Risk in Men with HIV

The Fracture Risk Assessment Tool (FRAX), an online tool developed by the World Health Organization and used to help guide decisions about who to screen or treat in order to prevent bone fractures, underestimates overall risk of fracture in people living with HIV -- even with an adjustment experts have recommended to improve its accuracy for people with HIV -- according to an analysis of the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: No HIV Transmissions from HIV+ Partners Seen in Australian Gay Couples Study

An Australia-based study of gay male couples of opposite HIV status (serodiscordant couples) has so far seen no transmissions from the HIV-positive partner within the couple in a 2-year interim analysis, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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