Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

OBJECTIVE: To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). DESIGN: Retrospective cohort study. SETTING: Three university medical centers, USA. POPULATION: HIV-infected pregnant women initiated or restarted on HAART during pregnancy. METHODS: We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. MAIN OUTCOME MEASURES: Time to HIV viral load <400 copies/ml and <1000 copies/ml. RESULTS: We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml. CONCLUSIONS: Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.

Sex worker health: San Francisco style.

OBJECTIVES: To describe the characteristics of sex workers accessing care at a peer based clinic in San Francisco and to evaluate predictors of sexually transmitted infections (STI). METHODS: We conducted an observational study of sex workers at St James Infirmary. Individuals underwent an initial questionnaire, and we offered screening for STI at each clinic visit. We performed univariate, bivariate, and multivariable analyses to assess for predictors of STI in this population. RESULTS: We saw 783 sex workers identifying as female (53.6%), male (23.9%), male to female transgender (16.1%), and other (6.5%). 70% had never disclosed their sex work to a medical provider. Participants represented a wide range of ethnicities, educational backgrounds, and types of sex work. The most common substance used was tobacco (45.8%). Nearly 40% reported current illicit drug use. Over half reported domestic violence, and 36.0% reported sex work related violence. Those screened had gonorrhoea (12.4%), chlamydia (6.8%), syphilis (1.8%), or herpes simplex virus 2 (34.3%). Predictors of STI included African-American race (odds ratio (OR) 3.3), male gender (OR 1.9), and sex work related violence (OR 1.9). In contrast, participants who had only ever engaged in collective sex work were less likely to have an STI (OR 0.4). CONCLUSIONS: The majority of sex workers have never discussed their work with a medical provider. Domestic violence is extremely prevalent as is work related violence. Working with other sex workers appears to be protective of STIs. STI prevention interventions should target African-American and male sex workers. Addressing violence in the workplace and encouraging sex workers to work collectively may be effective prevention strategies.

Health indicators among low income women who report a history of sex work: the population based Northern California Young Women's Survey.

OBJECTIVES: We examined differences in demographic characteristics, HIV related risk behaviour, prevalence of sexually transmitted infections (STI), and HIV and other health concerns among women with and without a history of sex work. METHODS: A secondary analysis of a population based, cross sectional survey of young, low income women in northern California. RESULTS: Of the 2543 women interviewed, 8.9% reported a history of sex work. These women reported more lifetime male sexual partners, were more likely to use drugs before sex, and were more likely to have a history of having sex with partners at high risk for HIV (that is, men who have sex with men, inject drugs, or were known to be HIV positive). They were significantly more likely to have positive serology for syphilis, herpes simplex virus type 2 (HSV-2), and hepatitis C regardless of their personal injecting drug use history; however, they were no more likely to have HIV, chlamydia, gonorrhoea, hepatitis A or hepatitis B infection compared to women without a history of sex work. Women with a history of sex work were significantly more likely to have a history of sexual coercion and tobacco use. CONCLUSIONS: These data measure the population prevalence of sex work among low income women and associated STI. Women with a history of sex work have health concerns beyond STI and HIV treatment and prevention.

Diarrheal disease in patients infected with human immunodeficiency virus in Bangkok, Thailand.

Diarrheal disease and its associated morbidities occur frequently in patients infected with human immunodeficiency virus (HIV) and may be associated with a decreased quality of life. We studied the spectrum of symptoms, measures of nutritional status, and the enteric pathogens associated with diarrheal disease in a group of 24 patients infected with HIV in Bangkok, Thailand compared with a group of 19 patients infected with HIV without diarrhea cared for at the same clinic. Patients with diarrhea appeared to have more advanced disease by CD4 cell counts and complained more frequently of symptoms such as anorexia, gas, and bloating than patients without diarrhea. Patients with diarrhea had a tendency toward a lower nutritional status, as measured by body mass index and mid arm circumference. Stool culture and examination revealed that enteric pathogens including Salmonella species and Cryptosporidium parvum sporidia were recovered at equal frequencies in patients with and without diarrhea (27% of the patients with diarrhea and 25% of the patients without diarrhea). Microsporidia was identified in one patient with diarrhea. It was not possible to identify a pathogen in 73% of the patients with diarrhea and 75% of the patients without diarrhea, suggesting that additional agents or factors may be responsible for the diarrheal symptoms in the patients with diarrhea. More extensive studies to identify potentially treatable pathogens in HIV-infected patients with diarrhea in Thailand are warranted and further attempts to better define the syndrome of pathogen-negative diarrheal disease in patients infected with HIV might result in the development of more targeted interventions in these patients.

Y2K compliance readiness and contingency planning.

As the millennium approaches, discussion of "Y2K compliance" will shift to discussion of "Y2K readiness." While "compliance" focuses on the technological functioning of one's own computers, "readiness" focuses on the operational planning required in a world of interdependence, in which the functionality of one's own computers is only part of the story. "Readiness" includes the ability to cope with potential Y2K failures of vendors, suppliers, staff, banks, utility companies, and others. Administrators must apply their traditional skills of analysis, inquiry and diligence to the manifold imaginable challenges which Y2K will thrust upon their facilities. The SPICE template can be used as a systematic tool to guide planning for this historic event.

Transferrin and the transferrin cycle in Belgrade rat reticulocytes.

Belgrade rats have an autosomal recessive anemia with hypochromia and microcytosis. Iron uptake into reticulocytes is approximately 20% of normal, but transferrin uptake is unimpaired. We have systematically compared the transferrin cycle in Belgrade versus normal reticulocytes to locate the defect more precisely. Belgrade transferrin was functionally normal as purified transferrin or whole plasma. Transferrin affinity of Belgrade receptors was indistinguishable from normal, but Belgrade reticulocytes had twice as many receptors. Belgrade transferrin endocytosis was 1.5 times faster than normal, whereas exocytosis is about twice as fast. Initially Belgrade reticulocytes internalize iron at an unimpaired rate, but they lag behind normal by 5 min. During reincubation, they release 25-33% of iron taken up during a 30-min preincubation, whereas normal cells do not lose a detectable fraction. Unexpectedly, transferrin cycle time was unchanged. Hence another kinetic step of the cycle is slower, compensating for increases in Belgrade endocytosis and exocytosis. After one cycle, Belgrade reticulocytes retain only half of the iron that entered, but over 90% of iron entering normal cells remains within. Iron unloading is ineffective inside the Belgrade vesicle; 85% of iron that entered on transferrin returned to the medium after exocytosis, whereas only 45% of iron entering normal reticulocytes exits. Ineffective utilization of iron in or near Belgrade endosomes accounts for the Belgrade defect.

Iron distribution in Belgrade rat reticulocytes after inhibition of heme synthesis with succinylacetone.

We have used succinylacetone (4,6-dioxoheptanoic acid), a specific inhibitor of delta-aminolevulinic acid dehydrase, to gain insight into the defect in iron metabolism in the Belgrade anemia. The Belgrade rat has an inherited microcytic, hypochromic anemia associated with poor iron uptake into developing erythroid cells. Succinylacetone inhibits heme synthesis, leading to nonheme iron accumulation in mitochondria and cytosol of normal reticulocytes. When succinylacetone is used to inhibit Belgrade heme synthesis, iron from diferric transferrin does not accumulate in the stromal fraction that contains mitochondria, nor does 59Fe accumulate in the nonheme cytosolic fraction. Hence, the defect in the Belgrade rat reticulocyte occurs in the endocytic vesicle or in a step subsequent to iron transit from the vesicle but before the nonheme cytosolic or mitochondrial iron fractions. Therefore, the mutation affects either the release of iron from transferrin or iron transport from the vesicle to the mitochondrion.