David D. Celentano

Association between Adherence to Antiretroviral Therapy and Human Immunodeficiency Virus Drug Resistance

Nonadherence to highly active antiretroviral therapy (HAART) is a major cause of human immunodeficiency virus (HIV) drug resistance; however the level of nonadherence associated with the greatest risk of resistance is unknown. Beginning in February 2000, 195 patients at the Johns Hopkins Outpatient Center (Baltimore, MD) who were receiving HAART and who had HIV loads of <500 copies/mL were recruited into a cohort study and observed for 1 year. At each visit, adherence to HAART was assessed and plasma samples were obtained and stored for resistance testing, if indicated. The overall incidence of viral rebound with clinically significant resistance was 14.5 cases per 100 person-years. By multivariate Cox proportional hazards regression, a cumulative adherence of 70%-89%, a CD4 cell nadir of <200 cells/microL, and the missing of a scheduled clinic visit in the past month were independently associated with an increased hazard of viral rebound with clinically significant resistance. Clinicians and patients must set high adherence goals to avoid the development of resistance.

Changes in Sexual Behavior and a Decline in HIV Infection among Young Men in Thailand

BACKGROUND In Thailand the epidemic of human immunodeficiency virus (HIV) infection is of recent origin. Because of the high seroprevalence of HIV among sex workers, the Ministry of Public Health began a program in 1990 and 1991 to promote the use of condoms during commercial sex. We evaluated the effect of this and other programs to prevent HIV infection in Thailand. METHODS Using direct interviews, we studied five cohorts of 21-year-old men from northern Thailand who were conscripted into the army by a lottery in 1991, 1993, and 1995. In all, 4311 men were tested for HIV antibodies by enzyme-linked immunosorbent assay, with confirmation by Western blot assay. RESULTS In the 1991 and 1993 cohorts, the prevalence of HIV infection was 10.4 to 12.5 percent. In 1995, it fell to 6.7 percent (P < 0.001). The seroprevalence was only 0.7 percent among men who did not have sexual relations with a sex worker before 1992. Over the study period, the proportion of men who reported having sexual relations with a sex worker fell from 81.4 percent to 63.8 percent (P < 0.001). From 1991 to 1995, the mens reported use of condoms during the most recent sexual contacts with sex workers increased from 61.0 percent to 92.5 percent (P < 0.001); and in 1995, 15.2 percent of men had a history of a sexually transmitted disease, as compared with 42.2 percent in 1991 (P < 0.001). CONCLUSIONS Public health programs in Thailand have led to substantial changes in sexual behavior among young men, especially an increased use of condoms, and the rate of new HIV infections has declined.

Condom use to prevent incident STDs: the validity of self-reported condom use.

Background Studies of sexual behavior and of interventions designed to reduce human immunodeficiency virus risk usually depend on self-report. Validation of self-reported condom use measures has not been previously reported in an urban population at high risk for sexually transmitted diseases and human immunodeficiency virus. Methods A prospective cohort study was performed in subjects recruited from sexually transmitted disease clinics in Baltimore. At enrollment, a questionnaire was administered that assessed human immunodeficiency virus risk factors and sexually transmitted disease history, and used a retrospective calendar to assess sexual events and condom use over the previous 30 days. Clinical evaluation was performed for sexually transmitted diseases. At follow-up 3 months later, the same procedures were repeated. Incident sexually transmitted diseases at follow-up were defined as new culture or serologically documented diagnoses of gonorrhea, chlamydia, syphilis, or trichomoniasis. Results In the 323 male and 275 female (total = 598) subjects who completed a follow-up visit, 21% reported using condoms for every act of sexual intercourse over the previous 30 days, 21% reported occasionally using condoms, and 59% reported not using condoms. At follow-up, 21% of subjects had new incident gonorrhea, chlamydia, syphilis, or trichomoniasis. Fifteen percent of the men who were “always” condom users had incident sexually transmitted diseases compared with 15.3% of “never users;” 23.5% of women who were “always” users had incident sexually transmitted diseases compared with 26.8% of “never” users. Conclusions In this high-risk population, self-reported condom use is not associated with lower sexually transmitted disease incidence. This finding suggests that self-reported condom use measures, even in a research setting, may be subject to substantial reporting bias.

Associations of Race/Ethnicity With HIV Prevalence and HIV-Related Behaviors Among Young Men Who Have Sex With Men in 7 Urban Centers in the United States

Abstract:Using data from a multisite venue-based survey of male subjects aged 15 to 22 years, we examined racial/ethnic differences in demographics, partner type, partner type-specific condom use, drug use, and HIV prevalence in 3316 US black, multiethnic black, Latino, and white men who have sex with men (MSM). We further estimated associations of these factors with HIV infection and their influence on racial/ethnic disparities in HIV prevalence. HIV prevalences were 16% for both black and multiethnic black participants, 6.9% for Latinos, and 3.3% for whites. Paradoxically, potentially risky sex and drug-using behaviors were generally reported most frequently by whites and least frequently by blacks. In a multiple logistic regression analysis, positive associations with HIV included older age, being out of school or work, sex while on crack cocaine, and anal sex with another male regardless of reported condom use level. Differences in these factors did not explain the racial/ethnic disparities in HIV prevalence, with both groups of blacks experiencing more than 9 times and Latinos experiencing approximately twice the fully adjusted odds of infection compared with whites. Understanding racial/ethnic disparities in HIV risk requires information beyond the traditional risk behavior and partnership type distinctions. Prevention programs should address risks in steady partnerships, target young men before sexual initiation with male partners, and tailor interventions to men of color and of lower socioeconomic status.

Unrecognized HIV infection, risk behaviors, and perceptions of risk among young men who have sex with men: opportunities for advancing HIV prevention in the third decade of HIV/AIDS.

This study evaluated the magnitude and distribution of unrecognized HIV infection among young men who have sex with men (MSM) and of those with unrecognized infection, the prevalence and correlates of unprotected anal intercourse (UAI), perceived low risk for infection, and delayed HIV testing. MSM aged 15-29 years were approached, interviewed, counseled, and tested for HIV at 263 randomly sampled venues in 6 US cities from 1994-2000. Of 5649 MSM participants, 573 (10%) tested positive for HIV. Of these, 91% of black, 69% of Hispanic, and 60% of white MSM (77% overall) were unaware of their infection. The 439 MSM with unrecognized infection reported a total of 2253 male sex partners in the previous 6 months; 51% had UAI; 59% perceived that they were at low risk for being infected; and 55% had not tested in the previous year. The HIV epidemic among MSM in the United States continues unabated, in part, because many young HIV-infected MSM are unaware of their infection and unknowingly expose their partners to HIV. To advance HIV prevention in the third decade of HIV/AIDS, prevention programs must reduce unrecognized infection among young MSM by increasing the demand for and availability of HIV testing services.

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

BACKGROUND Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. METHODS The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. FINDINGS 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373-522) cells per μL in patients assigned to the early treatment group and 428 (357-522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197-249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52-1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43-0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28-0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5-27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5-32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. INTERPRETATION Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment. FUNDING US National Institute of Allergy and Infectious Diseases.

Hormonal contraception and the risk of HIV acquisition

Background:Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. Objective:To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. Methods:This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18–35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15–24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). Results:HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69–1.42] nor DMPA (HR, 1.25; 95% CI, 0.89–1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39–5.82) and DMPA (HR, 3.97; 95% CI, 1.98–8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. Conclusions:No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.

A comparison of HIV/AIDS-related stigma in four countries: negative attitudes and perceived acts of discrimination towards people living with HIV/AIDS.

HIV/AIDS-related stigma and discrimination have a substantial impact on people living with HIV/AIDS (PLHA). The objectives of this study were: (1) to determine the associations of two constructs of HIV/AIDS-related stigma and discrimination (negative attitudes towards PLHA and perceived acts of discrimination towards PLHA) with previous history of HIV testing, knowledge of antiretroviral therapies (ARVs) and communication regarding HIV/AIDS and (2) to compare these two constructs across the five research sites with respect to differing levels of HIV prevalence and ARV coverage, using data presented from the baseline survey of U.S. National Institute of Mental Health (NIMH) Project Accept, a four-country HIV prevention trial in Sub-Saharan Africa (Tanzania, Zimbabwe and South Africa) and northern Thailand. A household probability sample of 14,203 participants completed a survey including a scale measuring HIV/AIDS-related stigma and discrimination. Logistic regression models determined the associations between negative attitudes and perceived discrimination with individual history of HIV testing, knowledge of ARVs and communication regarding HIV/AIDS. Spearmans correlation coefficients determined the relationships between negative attitudes and perceived discrimination and HIV prevalence and ARV coverage at the site-level. Negative attitudes were related to never having tested for HIV, lacking knowledge of ARVs, and never having discussed HIV/AIDS. More negative attitudes were found in sites with the lowest HIV prevalence (i.e., Tanzania and Thailand) and more perceived discrimination against PLHA was found in sites with the lowest ARV coverage (i.e., Tanzania and Zimbabwe). Programs that promote widespread HIV testing and discussion of HIV/AIDS, as well as education regarding and universal access to ARVs, may reduce HIV/AIDS-related stigma and discrimination.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

ObjectiveStudies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. MethodsA cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society–USA panel (IAS–USA) guidelines. ResultsBy 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. ConclusionsSelf-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Regional Patterns and Correlates of Substance Use Among Young Men Who Have Sex With Men in 7 US Urban Areas

OBJECTIVES We sought to characterize substance use patterns in young men who have sex with men (MSM) in 7 US urban areas and sociodemographic characteristics and history associated with such use. METHODS We examined data collected from 1994 through 1998 in a venue-based, cross-sectional survey. RESULTS Among the 3492 participants, 66% reported use of illicit drugs; 28%, use of 3 or more drugs; 29%, frequent drug use (once a week or more); and 4%, injection drug use. These practices were more common among participants who were White, self-identified as bisexual or heterosexual, had run away, or had experienced forced sex. CONCLUSIONS Effective drug prevention and treatment programs addressing local drug-use patterns and associated factors are urgently needed for young MSM, a population with a high rate of illicit drug use.