Stavudine Toxicity in Women Is the Main Reason for Treatment Change in a 3-Year Prospective Cohort of Adult Patients Started on First-Line Antiretroviral Treatment in Uganda.
In resource-limited settings, there are only a few antiretroviral treatment options. The objective was to evaluate the reasons for first-line antiretroviral therapy changes in resource-limited settings. The study was a prospective research cohort of patients initiating antiretroviral therapy between April 2004 and April 2005 in Kampala, Uganda. The main endpoint was the substitution of at least 1 drug included in the initial combination. Five hundred fifty-nine patients were initiated on antiretroviral therapy, 70% were female, median CD4+ count 98 (21-163) cells per microlitre, median HIV RNAlog10 5.4 (5.0-5.8). 413 (74%) patients were started on stavudine, lamivudine, and nevirapine, and 146 (36%) on zidovudine, lamivudine, and efavirenz. One hundred forty-eight (26.5%) had at least one treatment change (incidence rate 14.3 per 100 person-years; confidence interval: 12.2 to 16.9). The main reason for first treatment change was drug toxicity (n = 91, 61.5%). Stavudine accounted for the majority of the toxicities that led to drug substitution (n = 76, 84%).In the multivariate analysis, being female (P = 0.011) and being stage 3-4 as compared with 1-2 at antiretroviral therapy initiation were predictive of stavudine substitution (P = 0.05). There was no difference in virologic outcome in patients who changed due to toxicity compared with those who did not. The majority of the treatment changes were due to stavudine-related toxicity. Long-term stavudine use is less well tolerated in women.
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Editors’ note: In 2006 WHO recommended that the stavudine (d4T) dosage be reduced from 40 mg to 30 mg to reduce the risk of toxicity. In 2010 WHO recommended that countries move progressively away from including stavudine in their first-line regimens. As noted in our last issue, cumulative exposure to d4T may cause disfiguring lipodystrophy, painful peripheral neuropathy, and life threatening lactic acidosis (http://hivthisweek.unaids.org/post/treatment-4). This Ugandan prospective study shows that women are almost twice as likely as men to be switched from stavudine due to toxicity. The rate of substitution for lipodystrophy was ten times higher. Is this because women are more likely to report disfigurement; because women are at higher risk of the mitochondrial toxicity that causes lactic acidosis, lipodystrophy, and peripheral neuropathy; or because a standard 30 mg dose regardless of weight or sex is a disservice to them? As the Treatment 2.0 campaign begins to examine the possibility of reducing the dosage of various antiretroviral drugs, it would do well to consider whether dosages should be adjusted down differently for women.
Alcohol and HIV Disease Progression: Weighing the Evidence.
Hahn JA, Samet JH. Curr HIV/AIDS Rep. 2010 7:226-33
Heavy alcohol use is commonplace among HIV-infected individuals; however, the extent that alcohol use adversely impacts HIV disease progression has not been fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption results in behavioural and biological processes that likely increase HIV disease progression, and experimental evidence of the biological effect of heavy alcohol on simian immunodeficiency virus in macaques is quite suggestive. However, several observational studies of the effect of heavy alcohol consumption on HIV progression conducted in the 1990s found no association of heavy alcohol consumption with time to AIDS diagnosis, while some more recent studies showed associations of heavy alcohol consumption with declines of CD4 cell counts and nonsuppression of HIV viral load. The authors discuss several plausible biological and behavioural mechanisms by which alcohol may cause HIV disease progression, evidence from prospective observational human studies, and suggest future research to further illuminate this important issue.
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Editors’ note: What amount of alcohol intake is too much? The running joke answer is ‘More than what your physician drinks’. This review finds that, although there is strong biological plausibility that heavy alcohol intake might increase the rate of disease progression, it is difficult to demonstrate this in humans. In macaques, alcohol-exposed animals may consume fewer calories from food, have immune activation in the gut, and have higher viral loads at certain times but the association with increased progression of simian immunodeficiency virus infection has not been demonstrated. Heavy alcohol intake in human studies is defined as more than 4 drinks on any one occasion (3 for women) or more than 14 drinks a week (7 for women). Moderate drinking is anything between this level and abstinence. The strongest evidence linking alcohol intake and disease progression is the association between heavy alcohol intake and poor drug adherence. While you wait for scientists to disentangle any biological links between alcohol and disease progression, you can focus on the behavioural one – it would be smart to cut back on your drinking if you are having any trouble taking your medications regularly.
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