ARV Therapy and HIV Elimination

I'm waiting for my train in Ernakulum in an internet cafe that must be 40 degrees C. While sitting here sweating, I noticed a January 2009 Lancet article that has generated a lot of debate. The article (vol 373, issue 9657: 48-57) uses a theoretical model to asses whether testing everybody for HIV, then starting all positives on immediate ARV would eliminate HIV. [Note that the word "eliminate" does not mean the same as eradicate. They define eliminate as incidence of transmission less than 1 case per 1000 per year.] The idea of treatment as prevention is not new, of course, but this article takes it to the extreme. From the accompanying editorial:

In The Lancet today, Reuben Granich and colleagues (including two of us, KMDC and CFG) use mathematical modelling to assess the impact of expanded HIV testing and earlier antiretroviral therapy (ART) on HIV transmission.1 These researchers evaluated a theoretical programme of annual universal HIV testing and immediate treatment on HIV diagnosis, irrespective of CD4+ cell count, in an HIV epidemic with southern African population dynamics. The exercise suggested that HIV transmission could be substantially reduced within a few years. Elimination of HIV transmission, defined as an incidence below one case per 1000 population per year, could be achieved within a decade, and the overall prevalence of HIV infection reduced to below 1% before the middle of the century. Compared with current practice of starting ART at a specific CD4+ count, deaths would be halved between now and 2050.

The article generated a lot of interesting correspondence, some of which is published in vol 373, 9669. For me, the most important issue was raised in the letter by Jaffe et al:

In their important and provocative article,1 Reuben Granich and colleagues argue that universal voluntary HIV testing and immediate antiretroviral therapy, irrespective of the degree of immune suppression, could eliminate HIV from countries where the infection is highly prevalent. However, we agree with Geoffrey Garnett and Rebecca Baggaley2 that this approach could strongly shift the benefits of treatment from the individual to the population.

Although current HIV treatment guidelines favour earlier treatment, the risks and benefits of treatment for people with CD4+ cell counts above 350 per μL are unknown. Trials of therapy for patients with higher counts are yet to begin.

Within the field of communicable diseases, we are aware of little precedent for the approach of “treating for the common good”. Treatment of diseases such as tuberculosis might have the effect of decreasing transmission, but the primary goal is to decrease morbidity and mortality for the affected person. A better analogy might be found in immunisation programmes—eg, rubella vaccination of infants and children aims to reduce exposure among pregnant women. However, there is still a clear benefit and minimal risk for the individual vaccinee.

The World Medical Association international code of medical ethics states that “A physician shall act in the patient's best interest when providing medical care.”3 If we are to deviate from this basic principle, we will need a robust ethical model for balancing individual and societal benefits.

World TB Day 2009

World TB day came and went a few days ago, while I was stuck in Bihar up to my neck in kala-azar. Now I'm in Kerala, where nobody has kala-azar, but people are coughing up clouds of mycobacteria to my left and to my right. MSF access campaign published a beautiful summary document on the current challenges to TB control.

The White Tiger

I read The White Tiger, Aravind Adiga´s novel that won the 2008 Booker prize.

From the New Yorker review:

In this darkly comic début novel set in India, Balram, a chauffeur, murders his employer, justifying his crime as the act of a "social entrepreneur." In a series of letters to the Premier of China, in anticipation of the leader’s upcoming visit to Balram’s homeland, the chauffeur recounts his transformation from an honest, hardworking boy growing up in "the Darkness"—those areas of rural India where education and electricity are equally scarce, and where villagers banter about local elections "like eunuchs discussing the Kama Sutra"—to a determined killer. He places the blame for his rage squarely on the avarice of the Indian élite, among whom bribes are commonplace, and who perpetuate a system in which many are sacrificed to the whims of a few. Adiga’s message isn’t subtle or novel, but Balram’s appealingly sardonic voice and acute observations of the social order are both winning and unsettling.

The narrator of the book was born in Bihar--which he calls "the Darkness:"

I am talking about a place in India, at least a third of the country, a fertile place, full of rice fields and wheat fields and ponds in the middle of those fields choked with lotuses and water lilies, and water buffaloes wading though the ponds and chewing on the lotuses and lilies. Those who live in this place call it the Darkness. Please understand, York Excellency, that India is two countries in one: an India of Light and an India of Darkness. The ocean brings light to my country. Every place on the map of India neaer the ocean is well off. But the river brings darkness to India--the Black river.

Which black river am I talking of-- which river of Death whose banks are full of rich, dark, sticky mud whose grip traps everything that is planted in it, suffocating and choking and stunting it?

Why, I am talking of Mother Ganga, daughter of Vedas, river of illumination, protector of us all, breaker of the chain of birth and rebirth. Everywhere this river flows, that area is the Darkness.

One fact about India is that you can take almost anything you hear about the country from the prime Minister and turn it upside down and then you will have the truth about that thing. Now, you have heard that the Ganga called the river of emancipation, and hundreds of American tourists come each year to take photographs of naked sadhus at Hardwar or Benaras, and our prime minister will no doubt describe it that way to you, and urge you to take a dip in it.

No!--Mr Jiabao, I urge you not to dip in the Ganga, unless you want your mouth full of feces, straw, soggy parts of human bodies, buffalo carrion, and seven different kinds of industrial acids.

Kidnapped MSF Staff Released in Sudan

What a mess! A few days after MSF-Holland and MSF-France were ordered to leave Sudan last week, four staff members of MSF-Belgium were abducted. The Guardian report on the kidnapping is here. According to MSF´s press release, the four kidnapped staff members were released yesterday. Unfortunately, more MSF projects will evacuate after the kidnapping, and more IDPs in Darfur who depend on International Aid will suffer.

Follow-ups

As I mentioned in the last post, we see our patients at 3 months and 6 months after they have been discharged from the hospital. If fever and splenomegaly are still present at the follow-up visit, the patient may have relapsed. These patients need to come into the hospital for a splenic aspirate. Most patients are symptom free; these patients have been cured.

Despite the cost and the hassle, approximately 80% of our patients come back to the hospital for follow-up visits. If they don’t come back, we go out and look for them.

I went out with our follow-up team last week. It turns out that finding each patient is more difficult than you might think. The process involves going to nearest town and asking directions to the village. When we find the village, we need to ask if the patient is known there. Half the time, this involves a long discussion of the father’s name, the grandfather’s name, etc. A child is sent off to the fields to bring back the patient. Sometimes the person found is not the person we are looking for (e.g. same name but different age, height, etc). It took, on average, an hour or two to find each patient from the nearest town.

I enjoyed the follow-up visits, particularly because it took me from urban India to rural India. At each village, everybody stopped what they were dong to watch; there’s not much privacy in village life. Within minutes there was always a big crowd around us. Our health educators took each opportunity to educate the people about kala-azar. There were many questions.

Childhood Malnutrition in India

In the New York Times today, an article about malnutrition in India. MSF-Spain started a project last month in Darbhanga Bihar to treat malnourished children. I hope to visit the project while I am in Bihar.

Response to Treatment

In this project we are using Liposomal Amphoteracin B (brand name Ambisome) to treat kala-azar. We use this treatment because there is a high rate of resistance to SSG-- the standard first-line treatment—in Bihar state. The L. donovani parasite is exquisitely sensitive to Liposomal Amphoteracin B. Our treatment protocol uses four infusions of Ambisome; each dose is 5 mg/kg body weight. By the end of the second infusion, there is a dramatic improvement in the patients’ status. The fever curves pictured above are typical. [The temperature in degrees F is plotted on the y axis vs time on the x-axis.] In fact, if a patient remains febrile after the 2nd or 3rd dose, we are suspicious that the patient has another source of infection. The speed and magnitude of response is unusual in infectious disease treatment. In most bacterial infections, we see a much more gradual response to treatment; the peak of fever usually decreases gradually over the course of several days.

The response to Liposomal Amphoteracin treatment is also enduring. Of the first 2000 patients we treated in Bihar, 98% of patients are symptom free at the end of treatment. In order to demonstrate the efficacy of this treatment over time, we are careful to follow-up the patients we treat 3 months and 6 months after treatment. Careful follow-up is not the standard of care in Bihar. Most patients who feel well do not return to the hospital for check-ups. The journey is too long and expensive; it requires time away from childcare and work. Despite the challenges of follow-up, we work hard to find each patient in order to prove to skeptics that patients treated with Ambisome do not relapse after cure. In the first 250 patients treated in this project, we managed to find and examine 201 of them at 6 months. 96% of these patients were still symptom free, which satisfies our definition of complete cure of visceral leishmaniasis.

Aid Agencies Expelled From Darfur

I have not seen the news for the past few days. I just found out that MSF and 12 other aid organizations were expelled from Darfur. What an outrage! NPR's coverage here. MSF's press release here. Kristof's NY Times column here.

Stress Reduction

We cannot exercise outside in Hajipur. Locals would gape at us and laugh. The streets are crowded with traffic and sewage. Without exercise, I am at high risk for takeover by my dark side.

Anne and Othman hired a local yoga instructor to come to our house. He gives them lessons three times per week at 6:30 am. The only words of English he knows are “relax” and “leg.” The rest of the lesson is in Hindi. I tried some sessions, but I find that the stress from the language barrier outweighs the benefit of yoga. I’ve been jumping rope instead.

Still alive

I have not been able to post anything lately because our internet connection has been broken. I hope it stays alive long enough to upload this two sentence reassurance to family and friends: I´m surviving Bihar. Earplugs are serving me well. I miss you.