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Video-Observed Treatment Instead of Directly Observed Treatment for TB

Smartphone-enabled video observation of tuberculosis treatment (VOT) was effective and has multiple advantages over traditional directly observed therapy (DOT).  In the full follow-up period, completed observations were significantly higher in the VOT than DOT group (77% vs. 39%, respectively). 

Directly observed treatment (DOT) for tuberculosis (TB) has been recommended to improve treatment completion particularly among groups with poor adherence. Smartphone technology makes video-observed treatment (VOT) feasible. U.K. investigators compared TB treatment completion using traditional DOT versus asynchronous VOT (recorded video clips forwarded and reviewed later).

Investigators randomized patients aged ≥16 years with active TB (MDR-TB excluded to DOT [direct observation 3–5 times per week]) or VOT. VOT participants received smartphones and training to record and send videos of themselves taking medication. Trained observers assessed whether participants had taken doses. Smartphone participants could report adverse events and could call and text. More than half of both groups gave histories of homelessness, imprisonment, drug or alcohol problems, or mental health problems.

In intention-to-treat analysis, 70% of 112 VOT participants completed at least 80% of observations during first 2 months (including among those at increased risk for nonadherence) versus 31% of 114 on DOT. In the full follow-up period, completed observations were significantly higher in the VOT than DOT group (77% vs. 39%, respectively). Positive sputum cultures did not differ significantly between VOT and DOT at 2 months. Adverse events were reported by more VOT-group than DOT-group participants. VOT required less staff time and was cheaper than DOT.


Video-enabled TB treatment observation resulted in greater confirmed treatment compliance than DOT and achieved good results even in patients at high risk for poor adherence. VOT took less time for health workers and patients, was cheaper, and did not reduce identification of adverse events. The study was too small to detect differences in culture conversion or resistance development. It did not include patients with multidrug-resistant TB. This approach could have broad applicability as smartphone technology is widely available in most countries; good internet and cellular connections are needed. These results led U.K. National Health Service in London to adopt VOT.

Mary E. Wilson, MD reviewing Story A et al. Lancet 2019 Feb 21

EDITOR DISCLOSURES AT TIME OF PUBLICATION:  Disclosures for Mary E. Wilson, MD at time of publication: Consultant/Advisory Board : FXB Center for Health and Human Rights, Harvard T.H. Chan School of Public Health; Fogarty International Center

Royalties : UpToDate

Editorial Boards : Travel Medicine and Infectious Diseases; Journal of Travel Medicine

CITATION(S):Story A et al. Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: A multicentre, analyst-blinded, randomised, controlled superiority trial. Lancet 2019 Feb 21;


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Transmitted Resistance to All Integrase Inhibitors: A Rare Event, or the Tip of the Iceberg?

The first documented case of primary resistance to all integrase strand transfer inhibitors (INSTIs) in an ART-naive woman raises questions about universal screening for INSTI resistance.

Researchers present the case of a 42-year-old woman who had a negativeHIV test in August 2016 and was diagnosed with HIV infection in May 2018. She denied any history of antiretroviral therapy (ART), including pre- or postexposure prophylaxis.

A pretreatment genotype, including integrase sequencing, was obtained and showed three major INSTI mutations: E138A, G140S, and Q148H. These were also demonstrated on a repeat genotype. Subsequent genotypic sequencing of the presumed source patient, an HIV-infected sexual partner, revealed the same integrase mutations, confirming that this almost certainly represented transmitted integrase resistance. The source patient’s treatment history included raltegravir and dolutegravir.

INSTIs are now a component of every recommended initial regimen for ART-naive patients, per U.S. Department of Health and Human Services and International Antiviral Society -USA Panel guidelines.

This report leads us to ask once again if integrase resistance testing should be performed universally at HIV diagnosis. Despite this concerning case, the jury is still out, and the answer may depend on whether the initial regimen contains first- or second-generation INSTIs.

The first-generation agents, raltegravir and elvitegravir, have a lower barrier to resistance; multiple mutations to these agents can lead to cross-resistance to the second-generation agents, dolutegravir and bictegravir, as likely happened in the source patient.

Whether this mutational pattern would have led to virologic failure on a bictegravir- or dolutegravir-containing regimen is unknown, but a first-generation INSTI regimen would have been significantly compromised.

Modeling data (Clin Infect Dis 2017; 65:1274) suggest that baseline integrase resistance testing is not cost-effective and leads to worse clinical outcomes when the initial regimen contains a second-generation INSTI, but slightly better outcomes when a first-generation agent is selected. Continued monitoring of transmitted INSTI resistance is necessary and will help inform future recommendations.
EDITOR DISCLOSURES AT TIME OF PUBLICATIONDisclosures for Wendy S. Armstrong, MD at time of publicationNothing to disclose
CITATION(S):McGee KS et al. Canary in the coal mine? Transmitted mutations conferring resistance to all integrase strand transfer inhibitors in a treatment-naive patient. Open Forum Infect Dis 2018 Nov 8; 5:ofy294. (
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Improving HIV Self-Testing Among Male Partners of Pregnant Women in Malawi

A trial in Malawi showed that self-test kits given to pregnant women for their male partners along with a monetary incentive improved male HIV testing.

Salim S. Abdool Karim, MD, PhD reviewing Choko AT et al. PLoS Med 2019 Jan 2

A total of 2349 Malawian women attending a prenatal clinic for the first time during their current pregnancy were randomized to either a control standard-of-care arm (including a letter inviting the partner to test) or one of five intervention arms, all with two HIV self-test kits: either (1) the kits alone, (2) the kits with one of three levels of monetary incentive ($3, $10, or a 10% chance of receiving $30 in a lottery), or (3) the kits with a phone call reminder.

Interviewed at 28 days, women in the standard-of-care arm reported that 17.4% of their partners tested, while among the intervention arms, reported testing ranged from 87.0% to 95.4%. However, only 28.8% of male partners in the intervention arms had tested and were linked to treatment or prevention services within 28 days (the primary endpoint).

Testing rates among male partners of those receiving the HIV self-test alone or the test with a lottery entry were similar to those receiving the standard of care. However, partners of women receiving the HIV self-test kits in combination with the $3 or $10 monetary incentive or with a phone reminder were, respectively, 3.0, 3.7, and 1.6 times more likely than those in the standard-of-care arm to meet the primary endpoint.

The estimated program cost per man who tested and came to the health service was about $24 for those in the $3 incentive arm, while it cost about $28 per man in the $10 incentive arm.


In Malawi, HIV self-test kits, together with a $3 or $10 incentive or a phone call reminder, were effective in improving HIV testing rates with linkage to care or prevention for male partners of pregnant women. The strategy could be important in settings where men are hard to reach and have low testing coverage. Cost estimates indicate that this is an affordable strategy for Malawi.

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As A Strategy for HIV Prevention, Disabling the CCR5 Gene in Embryos Implanted in HIV-Negative Mothers Makes Zero Sense

Dr. Paul Sax weighs in on scientist He Jiankui’s “disturbing” gene-editing experiment, in HIV and ID Observations.

Chinese scientist He Jiankui recently announced he used an editing technique to alter the embryos of two babies. The research was initially described as an “AIDS vaccine development project.” But, points out Dr. Paul Sax in the latest HIV and ID Observations blog post, babies are not at risk for HIV, even if the mother’s male sexual partner has the virus.

Here are a bunch of things we know about HIV prevention, listed roughly in order of when we learned them — and forgive me if this is an oversimplification for this sophisticated readership:

  • Condoms work very well in preventing HIV transmission.
  • Taking a brief course of HIV therapy soon after exposure reduces the risk of HIV acquisition.
  • Babies born to HIV-positive mothers do not contract HIV if the moms take suppressive HIV therapy.
  • Male circumcision reduces the risk of these men acquiring HIV.
  • People do not contract HIV from their HIV-positive partners if the person with HIV takes suppressive HIV therapy.
  • People taking pre-exposure prophylaxis markedly reduce their risk for HIV acquisition.

You’ll note that nowhere on this list is anything about preventing HIV in babies born to women who don’t have the virus to begin with — because the babies are not at risk, even if the mother’s male sexual partner has HIV.

Just typing that sentence felt a little strange, it’s so obvious. However, it seems that He Jiankui may not understand this basic fact.

He’s the scientist who startled the world by releasing news that he and his research team had used CRISPR–Cas9 genome-editing to alter the embryos of two babies. The editing disabled the CCR5 gene, which means the babies lack a key co-receptor that HIV uses to infect cells.

However, as noted at 1:53 in the above-linked video, it’s the father who has HIV. Indeed, reports indicate that eight serodiscordant couples have participated in his studies — all with the fathers having HIV.

I’ll let others with far greater knowledge of genetics, embryology, and medical ethics comment on just how reckless this experiment was — here’s a good take (there have been many).

But from an HIV prevention perspective, it’s easy to judge — it makes zero sense to do this since the babies aren’t at risk of getting HIV to begin with. For them and their families, the genome-editing was all risk and no reward.

Let’s hope the mothers understood this before they agreed to participate in this disturbing experiment.

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More Evidence for Dolutegravir/Lamivudine as Initial HIV Therapy

In antiretroviral-naive adults with HIV infection, the two-drug regimen was noninferior to a standard three-drug regimen.

Two-drug antiretroviral therapy (ART)regimens for ART-naive adults with HIV infection are of considerable interest.Now, investigators have conducted two identical randomized, controlled trials(GEMINI 1 and 2) to evaluate what is currently the most promising two-drugcombination — dolutegravir/lamivudine — for ART-naive HIV-positive adults.


November 29, 2018

Wendy S. Armstrong, MD reviewing Cahn P et al. Lancet 2018 Nov 9

A total of 1441 participants wereassigned 1:1 to dolutegravir/lamivudine or a standard three-drug regimen:dolutegravir/tenofovir/emtricitabine. At enrollment, participants had viralloads of 1000 to 100,000 copies/mL (increased during the trial to an upperlimit of 500,000 copies/mL).

At 48 weeks, pooleddata from the intention-to-treat analysis demonstrated virologic suppression of<50 copies/mL in 91% in the two-drug group and 93% in the three-drug group,demonstrating non inferiority for the two-drug regimen. In subgroup analysis, no differences in rates of viral suppression were observed in those with viralloads >100,000 copies/mL, but rates of suppression were significantly lower in those with a baseline CD4 count <200 cell/mm3.

The latter group represented only 8%–9% of the total study population, and most endpoints did not represent virologic failure, limiting the interpretation of this finding.Among 10 patients who met criteria for virologic withdrawal (all with rebound),none developed mutations to agents in their treatment regimen.

COMMENTThe GEMINI studies add support to the use of dolutegravir/lamivudine as a two-drug regimen for initial treatment of adults with HIV infection, with important caveats: The studies excluded patients with viral loads >500,000 copies/mL, and the performance in those with CD4 counts <200 remains uncertain. Additional 96- and 144-week data analyses are planned to assess durability and experience in “real-world” patients to further clarify the risks for resistance. If these promising results are maintained, the most important advantage of this regimen is the potential for dramatic cost savings with the use of branded dolutegravir and generic lamivudine, which could introduce much needed price competition to the ART market.