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HIV & AIDS Treatment in Practice #4, 24 April 2003
A regular electronic newsletter for health care workers and community-based organisations on HIV treatment in resource-limited settings. It is supported by and produced in collaboration with St Stephen's AIDS Trust and the International HIV/AIDS Alliance.

Its publication is also supported by Positive Action of GlaxoSmithKline, Boehringer Ingelheim and the Access 4 Trust.
   Last updated: 18.06.04
IN THIS ISSUE
About HIV & AIDS Treatment in Practice
Update: Combining ARVs with Treatment for Tuberculosis
Update: Nevirapine-based Fixed-dose Combination ARVs
Update: Co-trimoxazole Prophylaxis
News links from www.aidsmap.com

This issue does not carry a main feature article, but reviews recent
publications and developments on subjects covered in previous issues.

The next three issues will feature articles about communicating
information on side effects, treatment for latent tuberculosis in people
with HIV, and monitoring treatment with ARVs where resources are limited.

Letters for publication from readers on any of the issues raised here
would be very welcome.

UPDATE: COMBINING ARVs WITH TREATMENT FOR TUBERCULOSIS
From HATIP #3 - click here to read original article

MANAGING IMMUNE RECONSTITUTION DISEASE

In comments that arrived after the last issue was sent out, Dr Desmond
Martin writes, from South Africa:

"Immune reconstitution disease (IRD, also known as Immune reconstitution
inflammatory syndrome, IRIS) is a topic of its own. We are seeing more and
more of this syndrome in our patients. In brief:

"If one is able to delay ARV treatment this will lead to a reduction in
the incidence of IRD. If however one is forced to commence ARV treatment
early in the course of the TB treatment one must have a heightened
awareness of the possibility of IRD and almost expect it to happen. It
seems to be a lot more common in our setting compared to areas where TB is
not endemic.

"The key things to watch out for are fever, pulmonary infiltrates,
abdominal pain, enlarging glands (both hilar or abdominal or elsewhere).
The typical scenario is a patient who commences ARVs in the face of
significant immunosuppression (CD4+ < 50). It can occur in patients who
were previously non-reactive on a Mantoux test. Remember in our setting
the majority of the population are likely to be positive to a Mantoux at
some stage of their lives and non-reactivity implies immunosuppression
[rather than not having been exposed to TB].

"Steroids are often used as an adjunct to therapy; I however am
ambivalent as to their use. One just has to sit tight on the situation and
see it through. I have used steroids in certain circumstances (e.g.
enlarging hilar node obstructing bronchus). When used the dose of
cortisone would be something like 40-60 mg daily, typically for four to six weeks."

WHEN DOES A NEGATIVE TB SKIN TEST MEAN "NOT EXPOSED"?

A research letter published in the most recent issue of AIDS reports a US
study which assessed the ability of 110 HIV positive patients to respond
to several antigens, including PPD (TB proteins), in relation to their CD4
counts. When the CD4 count was below 50, as many as one third were
anergic. When it rose between 50 and 100, the majority of those who had
previously been anergic became reactive, and when it rose above 100,
almost all were reactive. In this population, only 13 had been exposed to
TB, but these included two individuals who had tested negative when their
CD4 counts had been lower, before starting on ARV treatment. The
implication is likely to be, that negative skin test results for TB can
only be taken as truly negative when the CD4 count is above 100.

REFERENCE

Fisk TL et al. Detection of latent tuberculosis among HIV-infected
patients after initiation of highly active antiretroviral therapy. AIDS
17:1102-1104, 2003.

UPDATE: NEVIRAPINE-BASED FIXED-DOSE COMBINATION ARVs
From HATIP #2 - click here to read original article

The launch issue of TREAT Asia Review, a quarterly magazine from the US
charity AmFAR, carries an interview with Dr Yusuf Hamied, who chairs the
Indian generic drug company Cipla. Dr Hamied reveals that current sales of
the company's ARVs are sufficient to treat between 20,000 and 30,000
patients worldwide, of whom 5,000 to 10,000 are in India. Scaling up
production to treat much larger numbers would take time and depend on
advance commitments from public sector purchasers to buy the drugs.
However, Dr Hamied refused to be drawn on the lack of public sector
funding for ARV treatment in India as a reason why the great majority of
people with HIV in India are unable to access it.

“Last week,” said Dr Hamied, whose interview was published in March, “We
introduced a combination kit of two tablets and a capsule, to be taken
simultaneously once a day under the name Odivir. These three contain 3TC
[lamivudine], efavirenz, and sustained-release ddI [didanosine]. Now, that
combination is more expensive—just under $3 a day. But we will introduce
Triomune as a once-a-day combination kit for just over $1 a day.”

The introduction of once-daily Triomune would seem to depend on a
sustained release formulation of d4T (stavudine) – a formulation which the
international company Bristol-Myers Squibb is struggling to bring to the
market, despite obtaining a product license for it in Europe. It will be
interesting to see how well Cipla can meet this challenge. However, the
2NN study reported at the Retrovirus conference in Boston cast doubt over
the safety of once-daily full dose nevirapine, which seems to give rise to
a higher risk of hepatitis than when nevirapine is dosed twice daily. This
may limit demand for the product, even when technical problems in making
it are overcome.

For the full interview, follow this link.

UPDATE: CO-TRIMOXAZOLE PROPHYLAXIS
From HATIP #1 - click here to read original article.

EXPANDING THE EVIDENCE BASE FOR CO-TRIMOXAZOLE USE

The 2 May issue of the journal AIDS reports a study from Malawi (Zachariah
et al) which adds to the evidence that co-trimoxazole can reduce mortality
among people with HIV diagnosed with TB. This evidence is discussed by Dr
Peter Godfrey-Faussett of the London School of Hygiene and Tropical
Medicine in a related editorial.

Godfrey-Faussett's editorial sets out the challenge very starkly. In
Malawi, which closely follows WHO's DOTS strategy and has done so for many
years, "one in every three patients who starts anti-tuberculous
chemotherapy is dead before the end of the course". Given that three
quarters are HIV positive, the main reason is likely to be AIDS-related.

In 1999 two randomised controlled trials in Cote d'Ivoire found survival
benefits from offering co-trimoxazole prophylaxis to people with HIV whose
CD4 counts were below 500, or who had symptomatic HIV disease. This led to
the early cessation of other randomised controlled trials of
co-trimoxazole prophylaxis. This has left the evidence base weak and open
to argument (as expressed in the differences of view among our Advisory
Panel).

Reviewing the study (described below) Godfrey-Faussett argues that while
it adds to the evidence, it is still insufficient as a basis for national
policy. He proposes that Malawi and similar countries should respond by
rolling out a programme, district by district, and include an element of
randomisation when deciding which districts should start each year. In
this way, the evidence base could be strengthened further and serious
outstanding questions, such as the impact on community prevalence of
drug-resistant bacterial infections and malaria, might be answered.

The study by Zachariah and others – an international collaboration between
local healthcare staff, the Malawi National Tuberculosis Control
Programme, the NGO Medecins sans Frontieres and researchers in Luxembourg
and Liverpool, compares the experience of patients treated for TB before
the introduction of HIV counselling, testing, and cotrimoxazole
prophylaxis, with the experience in the same district once these services
had been provided.

Thyolo district, Malawi, has "one government hospital, a mission hospital,
and 18 health centres which are involved in TB control activities".
National guidelines for TB treatment were unchanged during the study,
although it is impossible to be certain that the standard of care did not
change in some way. Several additional staff were employed to provide HIV
VCT in this population and additional training for all staff was provided,
for example, on how to recognise and manage cotrimoxazole rashes. However,
an important feature of this study was that the extra input was kept to a
minimum, which means that the intervention should be relatively simple to
implement on a wider scale.

In the year from 1 July 1999, all 1061 TB patients in the district were
enrolled in the study and offered pre-test counselling and HIV testing –
the "intervention group". 90 per cent accepted HIV testing and 964 were
tested, of whom 740 (77%) were found to be HIV positive. Six died before
they were even able to receive the results.

Those who tested positive were offered cotrimoxazole - 400mg
sulphamethoxazole + 80mg trimethoprim, twice daily - in addition to
standard TB treatment. Exceptions were made for those with known allergies
to sulpha-containing drugs, pregnant women, women breastfeeding babies
under the age of 2 months, and babies of unknown HIV status. 13 who
declined to be told their HIV test results agreed to take cotrimoxazole
nonetheless; a delicate compromise which may say a lot about the
commitment of the clinical staff to their patients. Cotrimoxazole
treatment was provided to a total of 693 patients throughout TB treatment
and indefinitely afterwards. Adherence to the treatment seems to have been
excellent (evidence for this included positive urine tests for
trimethoprim). 14 patients (2%) had a dermatological reaction (a skin
rash), all within the first two months of treatment, all of which reversed
when treatment was stopped.

The control group, registered in the previous year, consisted of 925
patients. HIV prevalence in the control group was not measured, but in the
context of a still-rising HIV epidemic in Malawi would most likely have
been lower than in the intervention group.

Record-keeping and follow-up were of consistently high quality, which is a
credit to all of the staff concerned and to the National Tuberculosis
Control Programme.

Death rates in the first month of TB treatment were similarly high in both
groups, but by four months there was a clear advantage in favour of the
intervention group as a whole. The benefit of cotrimoxazole was however
limited in this study to those patients with smear-negative or
extra-pulmonary TB, who were probably the most immunosuppressed. (Also,
only 60% of HIV positive patients with smear-positive pulmonary TB took
cotrimoxazole.) The researchers calculate that to save one life during the
eight months of TB treatment, it would be necessary to treat 12.5 people
with cotrimoxazole.

REFERENCES

Godfrey-Faussett P. District-randomized phased implementation:
strengthening the evidence base for cotrimoxazole for HIV-positive
tuberculosis patients. AIDS 17:1079-1081, 2003.

Zachariah R et al. Voluntary counselling, HIV testing and adjunctive
cotrimoxaxole reduces mortality in tuberculosis patients in Thyolo,
Malawi. AIDS 17:1053-1061, 2003.

NEWS LINKS FROM WWW.AIDSMAP.COM
A selection of news stories which have appeared since 10 April 2003.

International Day of Action supports fight for HIV drugs in South Africa
  • Activist groups all over the world are planning demonstrations today in

support of South African peoples' demands for antiretroviral treatment,
led by the Treatment Action Campaign.

Medicines Control Council blocks generic anti-HIV drugs imports from
Swaziland into South Africa
  • The high cost of antiretroviral drugs sold in their own country has

forced possibly thousands of HIV positive South Africans to import lower
cost generics from Swazi Pharm, a company based in neighbouring Swaziland.
Recently, however, South Africa's Medicines Control Council (MCC) put an
abrupt halt to the practice, leaving many patients whose health had
stabilized on generic antiretroviral medications, stranded without
treatment. Yet many doctors and even South Africa's Treatment Action
Campaign support the MCC action.

SA HIV doctors say government policies on ARVs make their position
untenable
  • A group of South African public health doctors have written an open

letter to senior figures in the country's government saying that they can
no longer continue to work with "integrity" when so many of their
terminally ill HIV-positive patients do not have access to anti-HIV
medication.

Vitamins for breastfeeding HIV positive mums boost babies' health in Tanzania
  • The latest report from a Tanzanian study on giving vitamin supplements

to breastfeeding women has found that providing multivitamins (B, C and E)
to the women raised CD4 counts in their babies, regardless of HIV status,
reducing the babies' risk of diarrhoeal disease. The findings are
published in the latest edition of Clinical Infectious Diseases

Largest US pension fund tells Glaxo: license HIV drugs to poorest nations
  • Another major pension fund has added to the pressure on pharmaceutical

companies to cut the cost of antiretrovirals for the poorest nations.
California Public Employees Retirement System (CalPERS), which holds $760
million of GlaxoSmithKline stock, is calling on the company to review
whether it has made enough effort to reduce the cost of antiretroviral
therapy.

Fat loss on HIV therapy averages 13% a year, reports Australian group
  • Australian researchers have reported in detail on the natural history

of body fat and metabolic changes in people commencing antiretroviral
therapy. Their findings challenge the notion that body fat changes could
be linked to immune reconstitution, and show a strong association between
lipoatrophy (fat loss) and cholesterol levels, both at baseline and after
six months of therapy.



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