Efavirenz

African countries are facing serious financial and practical dilemmas over implementing recent World Health Organization (WHO) guidelines urging a shift away from d4T-based combinations for first-line antiretroviral treatment, the 2007 HIV Implementers' Meeting heard last week in Kigali, Rwanda.

The South African Public Sector strike has meant that many public sector patients with HIV may or already have had their treatment interrupted. This applies to antiretrovirals, as well as opportunistic illness treatment.

Women can take the anti-AIDS drug nevirapine to protect their unborn children without endangering their ability to undergo life-saving antiretroviral treatment later on, a new study has found.

Women who took a single dose of the non-nucleoside analogue (NNRTI), nevirapine (Viramune) to prevent mother-to-baby transmission of HIV have an immunological response to HAART comparable to women who did not use nevirapine in this way, according to a study presented to the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro on July 25th.

While generic production has brought down the prices of most first-line anti-retrovirals from over U10 000 (R70 000) in 2000 to as little as U150 (R1 050) per patient per year in June this year, prices of newer ARVs and formulations for children are up to 12 times higher.

Large numbers of desperate people with AIDS, who cannot afford antiretrovirals, are trying to drum up money to buy the drugs.

The international courier DHL is the latest multinational company to join the ranks of those providing services at no profit to assist in the roll-out of antiretroviral therapy with the announcement on May 5th that it is to provide non-profit courier services to deliver antiretrovirals.

The World Health Organisation has published new draft treatment guidelines for use in resource-limited setting, with an emphasis on the use of fixed dose drug combinations wherever possible. The guidelines are designed to encourage the scale-up of antiretroviral therapy in the absence of comprehensive laboratory monitoring. The guidelines recommend that drug combinations should use either efavirenz or nevirapine as cornerstones, with either AZT/3TC or d4T/3TC as the nucleoside analogue backbone. The guidelines are intended to help countries choose which drugs to use as the lead regimen in national programmes, but in practical terms it is likely that countries will need to maintain a formulary of the five drugs in order to allow switching between nevirapine and efavirenz, and between AZT and d4T, and to accommodate patients with tuberculosis and pregnant women. In practical terms, it is likely that the WHO guidelines will encourage very wide use of generic antiretrovirals manufactured in India and South Africa. Two weeks ago the Clinton Foundation announced that it had reached agreement with Indian and South African manufacturers to sell a fixed dose combination of d4T, 3TC and nevirapine for $132 a year to Mozambique, Tanzania, Rwanda and South Africa and nine Caribbean states. WHO also recommends a three tier approach to monitoring. At community heath centre level, rapid HIV antibody testing, haemoglobin testing and pregnancy testing are the only tests recommended. Haemoglobin testing is only necessary if AZT is included in the regimen, and it can be done using a haemoglobin colour scale published by WHO. Haemoglobin testing for anaemia is necessary because the condition can worsen when AZT treatment begins. Pregnancy testing is only needed if efavirenz is included in the regimen. At district hospital level, rapid HIV antibody testing and confirmatory testing using a second method are recommended, together with CD4 counting. WHO says it is committed to working with member states to make CD4 counting as widely available as possible. Full blood counts and liver enzyme measurements are also encouraged, as is sputum smear testing for tuberculosis. A full blood count and differentials is preferred to haemoglobin in this setting for measuring anaemia and neutropenia, and for calculating total lymphocyte counts where CD4 cell counting is not possible. Total lymphocyte count is judged to be a useful measure of immune system damage in symptomatic patients, but cannot be used for monitoring responses to treatment. Treatment failure can be judged by the appearance of new symptoms (not to be confused with immune reconstitution syndrome), or the recurrence of a previous opportunistic infection. If CD4 counting is available, the guidelines recommend that treatment should be switched if the CD4 cell count falls below the pre-treatment baseline, or falls at least 50% below its peak level. In either case, clinicians should rule out the effects of tuberculosis. Reinfection with TB could occur without treatment failure. Second line treatment should be based on ddI plus tenofovir or abacavir and either lopinavir/saquinavir or saquinavir/ritonavir. However, both require a secure cold chain for storage of the ritonavir element. Atazanavir, a new protease inhibitor which can be taken once daily and which does not require cold storage, is judged to be too new for use in resource-limited settings.( Source:aidmap 5 November 2003). http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2401 Links:http://www.who.int/hiv/pub/prev_care/draft/en/

A session on tuberculosis and HIV at the South African AIDS Conference in Durban last week, sponsored by CAPRISA - the Centre for the AIDS Programme of Research in South Africa - was largely given over to discussing a pilot project at the Prince Cyril Zulu Communicable Diseases Clinic (formerly, the Durban Chest Clinic), which could form the basis for a large scale programme to integrate ARV treatment with TB care. The pilot study for the planned START trial, as presented by Dr Chris Jack, enrolled 20 patients diagnosed with TB and HIV, 15 of them female, 5 male, to look at the feasibility of combining a once-daily triple combination of ARVs with a fixed-dose four-drug TB treatment regimen. The ARV regimen consists of ddI (didanosine), 3TC (lamivudine) and efavirenz, provided by the Indian generic company Cipla in a single blister pack as ‘Odivir’. The TB treatment, for the initial stage of treatment, was with 'Rifafour', containing rifampicin, isoniazid, pyrazinamide and ethambutol. Some patients also received co-trimoxazole prophylaxis, which is in fact recommended for all co-infected people and may be especially important when the CD4 count is below 200 (in this study, 6 of the patients were in that category). A presentation by two medical students highlighted the impact of the pilot treatment study on patients and staff at the clinic, making an important point about infrastructure for ARV delivery in South Africa and other countries. The majority of patients treated for TB in KwaZulu Natal are HIV positive. At present, if they survive to the end of six months treatment for TB, many die soon after, of other infectious diseases. This has demoralised both patients and staff, and led to poor completion rates for treatment. On the other hand, even the limited prospect of expanding access to ARVs represented by the planned trial has given new hope and a stronger incentive to persevere with TB treatment. A high proportion of patients at the clinic express willingness to take ARVs and the availability of ARVs definitely affects their readiness to be tested for HIV. Reviewing drug interactions, Dr Andy Gray observed that the clinical significance of the reduced blood levels of efavirenz seen when it is co-administered with rifampicin was sufficiently unclear, that clinical trials might be justified. Dr Quarraisha Abdool Karim, who introduced the session, observed that treatment for people with HIV who are coinfected with TB would be an essential strategy for targeting ARV treatment to those South Africans who could benefit most from it, and where the benefit to public health would be greatest. (Source: Julian Meldrum, AIDSMAP,12 August 2003) * For other news from the AIDS conference as reported by AIDSMAP see http://www.aidsmap.com