Charles M. Heilig

Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis

BACKGROUND We did a meta-analysis to assess factors associated with disparities in HIV infection in black men who have sex with men (MSM) in Canada, the UK, and the USA. METHODS We searched Embase, Medline, Google Scholar, and online conference proceedings from Jan 1, 1981, to Dec 31, 2011, for racial comparative studies with quantitative outcomes associated with HIV risk or HIV infection. Key words and Medical Subject Headings (US National Library of Medicine) relevant to race were cross-referenced with citations pertinent to homosexuality in Canada, the UK, and the USA. Data were aggregated across studies for every outcome of interest to estimate overall effect sizes, which were converted into summary ORs for 106,148 black MSM relative to 581,577 other MSM. FINDINGS We analysed seven studies from Canada, 13 from the UK, and 174 from the USA. In every country, black MSM were as likely to engage similarly in serodiscordant unprotected sex as other MSM. Black MSM in Canada and the USA were less likely than other MSM to have a history of substance use (odds ratio, OR, 0·53, 95% CI 0·38-0·75, for Canada and 0·67, 0·50-0·92, for the USA). Black MSM in the UK (1·86, 1·58-2·18) and the USA (3·00, 2·06-4·40) were more likely to be HIV positive than were other MSM, but HIV-positive black MSM in each country were less likely (22% in the UK and 60% in the USA) to initiate combination antiretroviral therapy (cART) than other HIV-positive MSM. US HIV-positive black MSM were also less likely to have health insurance, have a high CD4 count, adhere to cART, or be virally suppressed than were other US HIV-positive MSM. Notably, despite a two-fold greater odds of having any structural barrier that increases HIV risk (eg, unemployment, low income, previous incarceration, or less education) compared with other US MSM, US black MSM were more likely to report any preventive behaviour against HIV infection (1·39, 1·23-1·57). For outcomes associated with HIV infection, disparities were greatest for US black MSM versus other MSM for structural barriers, sex partner demographics (eg, age, race), and HIV care outcomes, whereas disparities were least for sexual risk outcomes. INTERPRETATION Similar racial disparities in HIV and sexually transmitted infections and cART initiation are seen in MSM in the UK and the USA. Elimination of disparities in HIV infection in black MSM cannot be accomplished without addressing structural barriers or differences in HIV clinical care access and outcomes. FUNDING None.

Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease.

An Algorithm for Tuberculosis Screening and Diagnosis in People with HIV

BACKGROUND Tuberculosis screening is recommended for people with human immunodeficiency virus (HIV) infection to facilitate early diagnosis and safe initiation of antiretroviral therapy and isoniazid preventive therapy. No internationally accepted, evidence-based guideline addresses the optimal means of conducting such screening, although screening for chronic cough is common. METHODS We consecutively enrolled people with HIV infection from eight outpatient clinics in Cambodia, Thailand, and Vietnam. For each patient, three samples of sputum and one each of urine, stool, blood, and lymph-node aspirate (for patients with lymphadenopathy) were obtained for mycobacterial culture. We compared the characteristics of patients who received a diagnosis of tuberculosis (on the basis of having one or more specimens that were culture-positive) with those of patients who did not have tuberculosis to derive an algorithm for screening and diagnosis. RESULTS Tuberculosis was diagnosed in 267 (15%) of 1748 patients (median CD4+ T-lymphocyte count, 242 per cubic millimeter; interquartile range, 82 to 396). The presence of a cough for 2 or 3 weeks or more during the preceding 4 weeks had a sensitivity of 22 to 33% for detecting tuberculosis. The presence of cough of any duration, fever of any duration, or night sweats lasting 3 or more weeks in the preceding 4 weeks was 93% sensitive and 36% specific for tuberculosis. In the 1199 patients with any of these symptoms, a combination of two negative sputum smears, a normal chest radiograph, and a CD4+ cell count of 350 or more per cubic millimeter helped to rule out a diagnosis of tuberculosis, whereas a positive diagnosis could be made only for the 113 patients (9%) with one or more positive sputum smears; mycobacterial culture was required for most other patients. CONCLUSIONS In persons with HIV infection, screening for tuberculosis should include asking questions about a combination of symptoms rather than only about chronic cough. It is likely that antiretroviral therapy and isoniazid preventive therapy can be started safely in people whose screening for all three symptoms is negative, whereas diagnosis in most others will require mycobacterial culture.

Yield of Acid-fast Smear and Mycobacterial Culture for Tuberculosis Diagnosis in People with Human Immunodeficiency Virus

RATIONALE The World Health Organization recently revised its recommendations for tuberculosis (TB) diagnosis in people with HIV. Most studies cited to support these policies involved HIV-uninfected patients and only evaluated sputum specimens. OBJECTIVES To evaluate the performance of acid-fast bacilli smear and mycobacterial culture on sputum and nonsputum specimens for TB diagnosis in a cross-sectional survey of HIV-infected patients. METHODS In Thailand and Vietnam, we enrolled people with HIV regardless of signs or symptoms. Enrolled patients provided three sputum, one urine, one stool, one blood, and, for patients with palpable peripheral adenopathy, one lymph node aspirate specimen for acid-fast bacilli microscopy and mycobacterial culture on solid and broth-based media. We classified any patient with at least one specimen culture positive for Mycobacterium tuberculosis as having TB. MEASUREMENTS AND MAIN RESULTS Of 1,060 patients enrolled, 147 (14%) had TB. Of 126 with pulmonary TB, the incremental yield of performing a third sputum smear over two smears was 2% (95% confidence interval, 0-6), 90 (71%) patients were detected on broth-based culture of the first sputum specimen, and an additional 21 (17%) and 12 (10%) patients were diagnosed with the second and third specimens cultured. Of 82 lymph nodes cultured, 34 (42%) grew M. tuberculosis. In patients with two negative sputum smears, broth-based culture of three sputum specimens had the highest yield of any testing strategy. CONCLUSIONS In people with HIV living in settings where mycobacterial culture is not routinely available to all patients, a third sputum smear adds little to the diagnosis of TB. Broth-based culture of three sputum specimens diagnoses most TB cases, and lymph node aspiration provides the highest incremental yield of any nonpulmonary specimen test for TB.

Common roots: a contextual review of HIV epidemics in black men who have sex with men across the African diaspora

Pooled estimates from across the African diaspora show that black men who have sex with men (MSM) are 15 times more likely to be HIV positive compared with general populations and 8·5 times more likely compared with black populations. Disparities in the prevalence of HIV infection are greater in African and Caribbean countries that criminalise homosexual activity than in those that do not criminalise such behaviour. With the exception of US and African epidemiological studies, most studies of black MSM mainly focus on outcomes associated with HIV behavioural risk rather than on prevalence, incidence, or undiagnosed infection. Nevertheless, black MSM across the African diaspora share common experiences such as discrimination, cultural norms valuing masculinity, concerns about confidentiality during HIV testing or treatment, low access to HIV drugs, threats of violence or incarceration, and few targeted HIV prevention resources.

Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus.

Persistent infection with high‐risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high‐risk types, such as HPV16, may be more persistent than other HPV types, and type‐specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV‐seropositive and 279 HIV‐seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993–2000). Type‐specific HPV infections were detected using MY09/MY11/HMB01‐based PCR and 26 HPV type‐specific probes. The estimated duration of type‐specific infections was measured from the first HPV‐positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow‐up. HRs for clearance of HPV16 and related types versus low‐risk HPV types were 0.79 (95% CI: 0.64–0.97) in HIV‐positive women and 0.86 (95% CI: 0.59–1.27) in HIV‐negative women. HRs for HPV18 versus low‐risk types were 0.80 (95% CI: 0.56–1.16) and 0.57 (95% CI: 0.22–1.45) for HIV‐positive and ‐negative women, respectively. HPV types within the high‐risk category had low estimated clearance rates relative to low‐risk types, but HRs were not substantially modified by HIV serostatus.

Cancer incidence in women with or at risk for HIV

The purpose of our study was to identify the types and rates of cancers seen in high‐risk human immunodeficiency virus (HIV)‐infected and HIV‐uninfected women. From 1993 to 1995, 1,310 women enrolled at four urban U.S. research sites in the HIV Epidemiology Research Study and were interviewed biannually to identify interval diagnoses and hospitalizations until study closure in March 2000. Cancer incidence data were collected through abstraction of medical records and death certificates. Of 871 HIV‐infected and 439 HIV‐uninfected women, 85% had a history of smoking and 50% a history of injection drug use. For our analysis, 4,180 person‐years were contributed by HIV‐infected women, and 2,308 person‐years by HIV‐uninfected women. HIV‐infected women had 8 non‐Hodgkins lymphomas, 5 invasive cervical cancers (ICC), 1 Kaposis sarcoma and 12 non‐AIDS defining cancers, including 4 lung cancers, compared with 4 cancers in HIV‐uninfected women including 1 lung cancer (all cancers, 6.22/1000 person‐years vs. 1.73/1000 person‐years, p = 0.01). CD4+ cell counts were above 200/mm3 in all women with ICC. HIV‐infected women with lung cancer were young smokers (mean age, 40 years), and all died within 6 months of diagnosis. Lung cancer occurred at twice the rate in HIV‐infected vs. uninfected women in the cohort and severalfold above expected in age‐ and race‐matched women in U.S. national data (incidence relative risk 6.39; 95% confidence interval 3.71, 11.02; p < 10−7). The frequent occurrence of cervical and lung cancers have important implications for the counseling (cigarette cessation), screening (PAP smears) and care of women with HIV infection, as they live longer because of current antiretroviral therapies. Published 2001 Wiley‐Liss, Inc.

The Effect of Highly Active Antiretroviral Therapy on Human Papillomavirus Clearance and Cervical Cytology

OBJECTIVE: To examine the association of highly active antiretroviral therapy (HAART) with human papillomavirus (HPV) clearance and progression or regression of cervical cytological abnormalities in women with human immunodeficiency virus (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV Epidemiology Research Study, an observational, multisite cohort study, were evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for cervical cytology. Testing for HPV was conducted by polymerase chain reaction. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals (CIs). Number needed to treat (NNT) at 2 years was calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial lesions, HAART was associated with an increased likelihood of HPV clearance (hazard ratio 4.5, 95% CI 1.2–16.3, NNT 22.4). Use of HAART was not associated with an increased likelihood of HPV clearance among women with normal cervical cytology (hazard ratio 1.7, 95% CI 0.9–3.1, NNT 6.5) or atypical squamous cells of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4–2.5, NNT 174.0). Use of HAART was not significantly associated with an increased likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0–1.7, NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6–1.0, NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology, HAART was associated with enhanced HPV clearance but not with Pap test regression. Close monitoring of women with HIV for cervical cytologic abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF EVIDENCE: II

Incident and persistent vulvovaginal candidiasis among human immunodeficiency virus-infected women: Risk factors and severity

OBJECTIVE To examine risk factors for vulvovaginal candidiasis among women with or at risk for human immunodeficiency virus (HIV) infection. METHODS Data were from 856 HIV-infected women and 421 at-risk uninfected women observed semiannually at four study sites from April 1993 through February 1999. At enrollment women were 15–55 years old and had no acquired immunodeficiency syndrome–defining conditions. Three definitions for vulvovaginal candidiasis of differing severity were constructed using data from vaginal Candida culture and Gram stains scored for yeast and three signs on pelvic examination (vulvovaginal edema, erythema, or discharge): 1) culture or Gram stain positivity plus at least one clinical sign, 2) culture or Gram stain positivity plus at least two clinical signs, and 3) visible yeast on Gram stain plus at least one clinical sign. RESULTS The prevalence and cumulative incidence of each definition of vulvovaginal candidiasis were greater among HIV-infected women than among women not infected with HIV (P < .01 for all comparisons). Stratified by status at the preceding visit, vulvovaginal candidiasis was most likely among women with prior vulvovaginal candidiasis, least likely among women without earlier Candida colonization, and intermediately likely among women with preceding subclinical Candida colonization. Among HIV-infected women, lower CD4 count and higher HIV viral load were associated with vulvovaginal candidiasis. Several other factors were independently associated with vulvovaginal candidiasis, with strong associations for diabetes mellitus and pregnancy in particular. Vulvovaginal candidiasis was not more severe among HIV-infected women. CONCLUSION Vulvovaginal candidiasis occurred with higher incidence and greater persistence, but not greater severity, among HIV-infected women.

Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies

BACKGROUND Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis. METHODS We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling. FINDINGS We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0·0001). Furthermore, conversion status at 6 months (adjusted OR 14·07 [95% CI 10·05-19·71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4·12 [95% CI 2·25-7·54]) or who had unknown HIV infection (3·59 [1·96-6·58]), but not in those who were HIV positive (0·38 [0·12-1·18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27·3% [95% confidence limit 16·6-41·4]) and high specificity (89·8% [82·3-94·4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91·8% [85·9-95·4]), but moderate specificity (57·8% [42·5-71·6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment. INTERPRETATION Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis. FUNDING US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention.