Coverage of the 12 th Conference on Retroviruses and Opportunistic Infection

The declining prevalence of HIV infection in Uganda has often been attributed to the abstinence-based “ABC plan”* and was cited by many including members of the Bush administration as the best strategy to prevent the spread of HIV. However, a recent study (Abstract 27 LB) demonstrated that the success of tackling the pandemic in Uganda has little to do with abstinence. This study analyzed the sexual behavior of 10,000 adults in 50 villages over a period of 10 years. The data demonstrated that the decrease in Uganda's HIV prevalence is associated primarily with an increase in condom use, with 50% of men and boys (age 15 to 49) consistently using condoms with their non-martial sex partner. There was no indication of an increase in abstinence or monogamy. So, condoms work! Which comes as little surprise to most medical and social personnel working in the field of HIV treatment and prevention.

The positive impact of antiretroviral medications in decreasing the rate of progression to AIDS and death among HIV positive patients is undeniable. For the first time a new study from Harvard Medical School, Boston, (abstract 143 LB) quantified the benefit of HAART and demonstrated that progress in HIV care has saved nearly 2 million years of life in the United States, since 1989. While early treatment from 1989 to 1990 for prevention of pneumocystis carinii pneumonia and mycobacterium avium prolonged the life of patients for only few months, introduction of HAART regimen permitted an increase of several years. The availability of prophylaxis treatment for pneumonia and mycobacterium combined with HAART added more than 10 years to the life of an HIV positive patient. The benefit of these treatments per person far exceeds those conferred to treatment of other chronic diseases, highlighting the importance of diagnosis, HIV care and continued research to develop efficient therapeutic agents. However, recent report from the Center for Disease Control (CDC) indicated that only 56% of eligible*a HIV positive patients, age 15 to 49, are receiving HAART in the United States (abstract 167). Significant proportions of those who do not receive treatment are not diagnosed (42%), therefore are unable to access appropriate prevention and treatment services. Considering the importance of diagnosis in prevention strategies, it is imperative to increase the number of people aware of their status. It is also equally important to find the reasons why eligible and diagnosed HIV positive people in the US are not receiving treatment.

The ambitious goal of the “3 by 5” initiative (the World Health Organization [WHO] in conjunction with UNAIDS) to treat 3 million people in resource poor countries by 2006 seems increasingly out of reach. The initiative was able to provide treatment to 25% (770,000 HIV positive patients) of 3 million people as of the end of 2004. Dr. Jim Yong Kim from WHO, in his keynote speech at the 12 th Annual Retrovirus Conference, stated “Please stop speculating whether we will make it or not, and do all you can to make it happen”. A central challenge to provide treatment in developing countries is to make quality HIV medicines and diagnostics affordable. Although prices of some WHO recommended first-line drugs have decreased by more than 95% in resource-poor countries, prices for second line regimens are still very high. The failure to provide drugs to more patients is also a reflection of a lack of commitment from political leaders.

While small African countries such as Zambia and Swaziland have made great efforts meetings their targets, for the 3x5 initiative to meet its objective, it would take a new level of political commitment. Particularly from leaders of India, Nigeria and South Africa, where 41% of the 5.1 million people in need of antiretroviral drugs currently reside. All governments should look at the example of Africa and realize that delay can spell disaster when dealing with AIDS. UNAIDS has reported that life expectancy in nine African countries has dropped to below 40 because of HIV disease. There are already 11 million orphans because of AIDS, while 6,500 people are dying each day and in 2004, 3.1 million Africans were newly infected. The report concluded that "If by 2025, millions of African people are still becoming infected with HIV each year, these scenarios suggest that it will not be because there was no choice, it will be because, collectively, there was insufficient political will to change behavior at all levels, from the institution, to the community, to the individual, and halt the forces driving the AIDS epidemic in Africa."

Metabolic disorders associated with a prolonged use of HAART

Challenges in scaling up treatment in women of child-bearing age may be compounded by emerging data on the high prevalence of resistance associated with single-dose nevirapine used to prevent HIV transmission from mother to infant. New study in 329 women in Abidjan, Cote d'Ivoire (abstract 72LB), showed that short courses of unique combination of antiretroviral therapy reduces mother-to-child transmission of HIV to less than 5% of newborns with lower prevalence of resistance in mothers. In this study, women in their 32 nd week of gestation were given Combivir (containing zidovudine and lamivudine) until delivery and 3 days following birth. At the time of birth, the mother was given a single dose of nevirapine. The newborn was treated with a single dose of nevirapine and zidovudine for one week. The rate of infection among newborn dropped to 5% and only 1% of mothers become resistant to nevirapine. Again, the cost of drug combination compared to single dose nevirapine could still be prohibitive in some resource poor countries. In light of new studies, WHO is expected to broaden its guidelines for prevention of mother-to-child transmission and include new regimen in addition to single dose nevirapine and an AZT-nevirapine regimen.

Liposdystrophy

Thymidine-sparing regimen improve lipoatrophy (Abstract 45LB)

Two studies demonstrated clearly that switching to a thymidine-sparing regimen could improve lipoatrophy while maintaining virologic control. Dr. Murphy (Northwestern University) presented data from 101 patients at 15 ACTG sites. HIV positive patients receiving a thymidine analogue, stavudine (d4T) or zidovudine containing regimen with HIV RNA < 500 copies/ml and evidence of lipoatrophy were randomized to the following groups: 1. Switch to abacavir; 2. Discontinue all HAART and switch to lopinavir/ritonavir (LPV/r) plus nevirapine (NVP) (regimen without NRTIs); or 3. Delay switching for 24 weeks. At week 24 there was an increase in subcutaneous thigh fat in the LPV/r+NVP group. There was a significant increase in subcutaneous abdominal fat tissue and a decrease in visceral adipose tissue in the abacavir group. Those who delayed switching saw further loss in limb fat distribution. So, in patients with lipoatrophy, switching d4T or zidovudine to a non-thymidine analog or changing to an NRTI-sparing regimen significantly improve the abdominal, visceral and total adipose tissue distribution while increasing CD4 cell count and maintaining virologic control. The second study (Abstract 44LB), investigated changes in limb fat following substitution of zidovudine or d4T with abacavir versus tenofivir in 105 patients with moderate to severe lipoatrophy. The results clearly demonstrated that switching from a thymidine analog to abacavir or tenofovir for 48 weeks leads to similar increase in limb fat. However tenofovir is associated with fewer treatment discontinuations and a greater improvement in lipoatrophy than abacavir.

Maxepa® a fish oil reduces LDL and cholesterol (Abstract 39)

Dr. de Truchis, University of Paris, France, presented data showing that a formulation of fish oils rich in omega-3 fatty acids (Maxepa Ò ) can reduce low-density lipoprotein (LDL), cholesterol and triglyceride levels in adults with HIV infection. In this study, 122 patients on HAART were randomized to receive either two 1 g capsules of fish oil 3 times a day or placebo for 8 weeks, followed by 8 weeks of open-label fish-oil treatment for all patients. Patients (58) randomized to receive fish oil experienced a median 26% reduction in triglyceride levels, compared with a 1% increase in the placebo group (P = .003). Triglyceride levels normalized in 22% of fish-oil recipients compared to 7% in the placebo group ( P = .012). The reduction in triglyceride levels was sustained during the follow-up open-label treatment period among those originally randomized to fish oil, while median levels decreased by 21.2% among those who originally received placebo. There were no changes in total or high-density lipoprotein (HDL) cholesterol over the course of the study in either group. Furthermore, 10 patients with baseline triglycerides above 10 g/L experienced a 44% reduction in triglycerides after 8 weeks of open-label treatment phase with fish oil, demonstrating that fish oil is even effective in patients with severe elevations in blood lipids.

Myocardial Infraction and HAART (Abstract 42)

New study from the University of Copenhagen, Denmark, demonstrated a relationship between prolonged antiretroviral therapy and occurrence of Myocardial Infarction (MI). In this study, 23,441 HIV positive patients from 11 cohorts in Europe, Australia, and the United States were followed from 1999 to 2004, to determine the rates of MI (per 1000 person/year) and relative rates of factors associates with MI. By 2004 the mean exposure time to HAART was 4.46 years. The MI incidence increased from 1.39/1000 patients/year in treatment naive patients compared to 2.53/1000/year in those under treatment for less than one year and 6.07/patient/years in those exposed to HAART for over 6 years. After adjustment for other risk factors, there was a 1.17-fold increase in the risk of MI incidence per additional year of exposure to HAART. The relative increase in risk of MI appears to be similar in men and women as well as in older and younger patients. Controlling for levels of serum cholesterol, HDL cholesterol and triglyceride reduced the association of additional year of HAART with MI to 1.1/patient/year. Therefore, dislipedemia can account for part of the increase in MI incidence proportional to prolonged therapy.