HIV This Week

Clark R. Considerations for the antiretroviral management of women in 2008. Womens Health (Lond Engl). 2008;4(5):465-77.

Clinicians should be familiar with sex-specific considerations when managing antiretroviral treatment among women. Pregnancy is a critical influence on when to start treatment and what antiretroviral treatment should be included in a regimen. Sex, pregnancy and hormonal contraceptive therapies can each influence antiretroviral pharmacokinetic profiles. Women may be prone to have higher serum levels with selected antiretroviral treatments, which may improve potency but also increase the risk for toxicities. Several studies have demonstrated that women do have higher frequencies of selected antiretroviral -associated adverse events when compared with men. Although HIV treatment guidelines for nonpregnant women do not differ from men, clinicians should be aware of the high potential for certain antiretroviral -related toxicities and follow suggestions in order to decrease the risk of side effects.

Editors’ note: This summary of the literature and the US guidelines on antiretroviral treatment brings research gaps into sharp relief. Studies statistically powered to look at associations between age, HIV treatment, and outcomes by sex can help determine the trade-off for women between survival benefits and long-term toxicities. More study is needed of the safety of antiretroviral treatment discontinuation after pregnancy in women with higher CD4 cell counts, interactions between antiretroviral treatment and hormonal contraception, and the determinants of plasma-genital secretion viral load and viral sequence disconnects in women.

De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2008 Dec. [Epub ahead of print]

In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development.

Editors’ note: For readers who enjoyed biochemistry in the past or would like to learn more in the present, this article contains structural formulae, colourful 3-D depictions of docking by individual drugs, and clear descriptions of mechanisms of action by drug class. Those interested in history will find the dates of FDA approval for each drug, along with its manufacturer and generic and brand names, as well as a timeline showing the evolution of fixed-dose combinations.

DeSilva MB, Merry SP, Fischer PR, Rohrer JE, Isichei CO, Cha SS. Youth, unemployment, and male gender predict mortality in AIDS patients started on HAART in Nigeria. AIDS Care. 2009;21(1):70-7.

This retrospective study identifies risk factors for mortality in a cohort of HIV-positive adult patients treated with highly active antiretroviral therapy in Jos, Nigeria. DeSilva and colleagues analyzed clinical data from a cohort of 1552 patients enrolled in an HIV treatment programme and started on antiretroviral treatment between December 2004 and 30 April 2006. Death was the study endpoint. Patients were followed in the study until death, being lost to follow-up, or the end of data collection, 1 December 2006. Baseline patient characteristics were compared using Wilcoxon Rank Sum Test for continuous variables and Pearson Chi-Square test for categorical variables to determine if certain demographic factors were associated with more rapid progression to death. The Cox proportional hazards multivariate model analysis was used to find risk factors. As of 1 December 2006, a total of 104 cases progressed to death. In addition to the expected association of CD4 count less than 50 at initiation of therapy and active tuberculosis with mortality, the patient characteristics independently associated with a more rapid progression to death after initiation of antiretroviral treatment were male gender, age less than 30 years old, and unemployment or unknown occupation status. Future research is needed to identify the confounding variables that may be amenable to targeted interventions aimed at ameliorating these health disparities.

Editors’ note: In this retrospective cohort study of patients on antiretroviral treatment in one clinic, there was high loss to follow-up (8.8% over 23 months). Treatment adherence was not recorded for all patients and adequate nutrition was not measured, both of which are known to influence survival. However, the findings warrant further research, including qualitative studies, to assist in programme design to minimise loss to follow-up and prevent excessive mortality, particularly for young or unemployed men.