Sensitivity and specificity of rapid HIV testing of pregnant women in India.

OBJECTIVE: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India.

Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested case-control study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow-up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1; p =.01). No such association was observed in case of other non-provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.

Trends in crime and the introduction of a needle exchange program.

OBJECTIVES: This study sought to determine whether introduction of a needle exchange program would be associated with increased crime rates. METHODS: Trends in arrests were compared in program and nonprogram areas before and after introduction of a needle exchange program in Baltimore. Trends were modeled and compared via Poisson regression. RESULTS: No significant differences in arrest trends emerged. Over the study period, increases in category-specific arrests in program and nonprogram areas, respectively, were as follows: drug possession, 17.7% and 13.4%; economically motivated offenses, 0.0% and 20.7%; resistance to police authority, 0.0% and 5.3%; and violent offenses, 7.2% and 8.0%. CONCLUSIONS: The lack of association of overall and type-specific arrest data with program implementation argues against the role of needle exchange programs in increasing crime rates.

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.

Risk factors and clinical presentation of acute primary HIV infection in India.

CONTEXT: Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias. OBJECTIVES: To apply a method based on measurement of prevalent HIV-1 p24 antigenemia for identification of risk factors for newly acquired HIV infection and to describe the signs and symptoms of acute HIV infection. DESIGN AND SETTING: Nested case-control study in Pune, India. PARTICIPANTS: HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996. OUTCOME MEASURES: Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection. RESULTS: Of 3874 HIV antibody-negative persons tested, 58 (1.5%) were p24 antigen positive at initial presentation to the clinics. Unprotected sexual contact with a commercial sex worker (CSW) was reported by 39 (77%) of the 51 p24 antigenemic men, compared with 131 (51 %) of 255 control men (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.2-9.6; P=.02). The presence of an active genital ulcer at the time of screening was found in 46 (79%) of the 58 p24 antigenemic men and women, compared with 137 (47%) of the 290 control subjects (AOR, 4.2; 95% CI, 2.0-9.0; P<.001). Signs and symptoms independently associated with p24 antigenemia in HIV antibody-seronegative persons included fever, which was reported by 28 (48%) of the 58 p24 antigenemic subjects, but only 52 (18%) of the 290 control subjects (AOR, 4.7; 95% CI, 2.4-9.0; P<.001). Joint pain was reported by 10% of subjects recently HIV infected, compared with 2% of the control subjects (AOR, 6.5; 95% CI, 1.7-24.8; P=.006). Night sweats were reported by 9% of the p24 antigenemic, but only 1% of the control subjects (AOR, 9.1; 95% CI, 1.7-47.6; P=.009). Overall, fever, joint pain, and/or night sweats were reported in 27 (47%) of the 58 subjects with recent HIV infection. CONCLUSIONS: This systematic case-control study of p24 antigen screening in HIV-seronegative patients attending STD clinics in India identified unprotected sex with a CSW and a genital ulcer as independent risk factors associated with newly acquired HIV infection. In addition, p24 antigen positivity identified recent fever, night sweats, and arthralgias as symptoms that may be predictive of recent HIV infection. In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection.

Incidence and predictors of human immunodeficiency virus type 1 seroconversion in patients attending sexually transmitted disease clinics in India.

The first estimates of the seroincidence of human immunodeficiency virus type 1 (HIV-1) and of the risk factors for seroconversion in a cohort of high-risk patients attending sexually transmitted disease (STD) clinics in India are reported. Between 1993 and 1995, 851 HIV-1-seronegative persons were evaluated prospectively every 3 months for HIV infection and biologic and behavioral characteristics. The overall incidence of HIV-1 was 10.2/100 person-years (95% confidence interval, 7.9-13.1). The incidence among commercial sex workers (CSWs) was 26.1/100 person-years, compared with 8.4 among non-CSWs. Recurrent genital ulcer disease and urethritis or cervicitis during the follow-up period were independently associated with a 7- (P < .001) and 3-fold (P = .06) increased risk of HIV-1 seroconversion, respectively. Because of the association of recurrent ulcerative and nonulcerative STDs with HIV-1 seroconversion in this setting, behavioral and biologic measures directed at the prevention and control of STDs would be expected to greatly reduce the transmission of HIV-1 infection in similar high-risk groups.

Risk factors for HIV infection in people attending clinics for sexually transmitted diseases in India.

OBJECTIVE: To investigate the risk factors for HIV infection in patients attending clinics for sexually transmitted diseases in India. DESIGN: Descriptive study of HIV serology, risk behaviour, and findings on physical examination. SUBJECTS: 2800 patients presenting to outpatient clinics between 13 May 1993 and 15 July 1994. SETTING: Two clinics and the National AIDS Research Institute, in Pune, Maharashtra State, India. MAIN OUTCOME MEASURE: HIV status, presence of sexually transmitted diseases, and sexual behaviour. RESULTS: The overall proportion of patients infected with HIV was 23.4% (655/2800); 34% (184) of the women and 21% (459) of the men were positive for HIV infection. Of the 560 women screened, 338 (60%) had a reported history of sex working, of whom 153 (45%) were infected with HIV-1. The prevalence of HIV-1 infection in the 222 women who were not sex workers was 14%. The significant independent characteristics associated with HIV infection based on a logistic regression analysis included being a female sex worker, sexual contact with a sex worker, lack of formal education, receptive anal sex in the previous three months, lack of condom use in the previous three months, current or previous genital ulcer or genital discharge, and a positive result of a Venereal Disease Research Laboratory test. CONCLUSIONS: In India the prevalence of HIV infection is alarmingly high among female sex workers and men attending clinics for sexually transmitted diseases, particularly in those who had recently had contact with sex workers. A high prevalence of HIV infection was also found in monogamous, married women presenting to the clinics who denied any history of sex working. The HIV epidemic in India is primarily due to heterosexual transmission of HIV-1 and, as in other countries, HIV infection is associated with ulcerative and non-ulcerative sexually transmitted diseases.

PIP: During May 1994-July 1995 in India, health workers at two clinics for sexually transmitted diseases (STDs) in Pune provided HIV serological screening and a physical examination to 2800 patients who completed a questionnaire, so that researchers could identify risk factors for HIV-1 infection in this high-risk population. 60% of the female STD patients were sex workers. 90% of the men had contact with a sex worker within the last 3 months. 14% of all STD patients were women who were not sex workers. 82% of these were married and monogamous. 13% of the married and monogamous women tested positive for HIV-1. Overall, 23.4% of all STD patients tested positive for HIV-1. Only 24% of all STD patients had used condoms during the last 3 months. The leading clinical diagnosis was chancroid (33% for men and 20% for women). The logistic regression analysis showed that the risk factors for HIV-1 infection were: being a sex worker (odds ratio [OR] = 3.7; p 0.001), contact with a sex worker (OR = 1.71; p = 0.01), receptive anal sex (OR = 3.52; p 0.001), tattooed after 1985 (OR = 1.31; p = 0.01), current or previous genital ulcer (OR = 1.29; p = 0.01), and a positive result of a Venereal Disease Research Laboratory test (OR = 1.33; p = 0.01). Protective factors were some formal education (OR = 0.76; p = 0.02), and condom use (sometimes/always, OR = 0.75; p = 0.03). These findings indicate a need for comprehensive and national STD services in India to control STDs and a health education campaign on HIV/AIDS to reduce high risk behavior.

Reoperation on prosthetic heart values. Patient-specific estimates of in-hospital events.

Reoperation on prosthetic heart valves is increasingly under consideration for both clinical and prophylactic indications. To determine the correlates of hospital events, including in-hospital mortality, new persisting neurologic deficit, and length of postoperative stay, a three-institution study of 2246 consecutive prosthetic valve reoperations performed on 1984 patients between 1963 and 1992 was undertaken. The combined experience ranged from high-risk patients coming moribund to the operating room to an important number of well individuals undergoing prophylactic reoperations on potentially failing valves. The risk-unadjusted hospital mortality was 10.8%, neurologic deficit at hospital discharge 1.1%, and length of stay 10 days (median). Multivariably determined correlates of outcome included age at reoperation, degree, severity, and acuity of impairment of cardiac function, extensiveness of valvular heart disease, coexisting morbid conditions, number of previous heart operations, and concomitant procedures. The risk-adjusted hospital mortality for the first elective reoperation in a good-risk patient was 1.3% (90% confidence limits 0.3% to 4.4%), neurologic deficit 0.3% (90% confidence limits 0.02% to 1.8%), and length of postoperative stay 7 days (90% confidence limits 4 to 13), emphasizing the wide variance in outcome events. Equations were developed to permit wide application of the results of the study for quantitatively estimating the risk of outcome events based on individual preoperative patient characteristics. These estimates should be useful for informed patient consent, considerations of prophylactic valve replacement, and cost and resource use.

Validation of self-administered questionnaire for study of peripheral neuropathy.

An eight-item, self-administered questionnaire for the ascertainment of peripheral neuropathies was validated with 19 persons who had neuropathy confirmed by neurologists' examinations and electrodiagnostic studies, and with 37 persons without known neuropathy. The results from cases and neurology clinic controls suggested a two-stage screening definition for cases of peripheral neuropathy: the classification as cases of all persons who required help getting out of a chair one or more days/week and, among those not requiring help, who had a symptom score of zero or more based on the formula Si = -2.6 + 0.8 (frequency of cramps in arms or legs) + 0.5 (frequency of paresthesias in arms, hands, legs, or feet). This case definition resulted in a sensitivity of 76.5% and a specificity of 93.3% when applied to the original data from which it was developed. The statistical technique of cross-validation suggested an upward bias in these estimates of sensitivity and specificity of 12% and 20%, respectively. The model had a specificity of 100% when tested independently with medical office controls. The authors discuss the use of the questionnaire in cross-sectional epidemiologic studies.