Predictors of early and late mother-to-child transmission of HIV in a breastfeeding population: HIV Network for Prevention Trials 012 experience, Kampala, Uganda.

OBJECTIVE: To determine the predictors for early versus later (breastfeeding) transmission of HIV-1. METHODS: Secondary data analysis was performed on HIV Network for Prevention Trials 012, a completed randomized clinical trial assessing the relative efficacy of nevirapine (NVP) versus zidovudine in reducing mother-to-child transmission (MTCT) of HIV-1. We used Cox regression analysis to assess risk factors for MTCT. The ViroSeq HIV genotyping and a sensitive point mutation assay were used to detect NVP resistance mutations. RESULTS: In this subset analyses, 122 of 610 infants were HIV infected, of whom 99 (81.1%) were infected early (first positive polymerase chain reaction < or =56 days). Incidence of MTCT after 56 days was low [0.7% per month (95% confidence interval, CI: 0.4 to 1.0)], but continued through 18 months. In multivariate analyses, early MTCT "factors" included NVP versus zidovudine (hazard ratio (HR) = 0.57, 95% CI: 0.38 to 0.86), pre-entry maternal viral load (VL, HR = 1.76, 95% CI: 1.28 to 2.41), and CD4 cell count (HR = 1.16, 95% CI: 1.05 to 1.28). Maternal VL (6-8 weeks) was associated with late MTCT (HR = 3.66, 95% CI: 1.78 to 7.50), whereas maternal NVP resistance (6-8 weeks) was not. CONCLUSIONS: Maternal VL was the best predictor of both early and late transmission. Maternal NVP resistance at 6-8 weeks did not predict late transmission.

Unprotected sex following HIV testing among women in Uganda and Zimbabwe: short- and long-term comparisons with pre-test behaviour.

BACKGROUND: Despite widespread condom promotion for HIV prevention, prospective measurement of condom use before and after HIV testing is infrequent. METHODS: We analysed data from a prospective study of hormonal contraception and HIV acquisition among Zimbabwean and Ugandan women (1999-2004), in which HIV testing and counselling were performed approximately every 3 months. We used zero-inflated negative binomial (ZINB) models to examine the number and proportion of unprotected sex acts, comparing behaviour reported 2-6 months before HIV testing with behaviour reported both 2-6 months (short-term analysis) and 12-16 months (long-term analysis) after HIV testing. RESULTS: Short- and long-term analyses were similar, so we present only long-term findings from 151 HIV-infected and 650 uninfected participants. The proportion of HIV-infected women reporting any unprotected acts in a typical month declined from 74% (pre-infection behaviour) to 56% (12-16 months after HIV diagnosis). In multivariable models, HIV-infected women were twice as likely to report that all sex acts were protected by condoms after diagnosis compared with beforehand [adjusted odds ratio (aOR): 1.99, 95% confidence interval (CI): 1.12-3.53]; uninfected women were somewhat less likely to report that all acts were protected (aOR: 0.82, 95% CI: 0.64-1.04). HIV-infected women also reduced their number of unprotected acts by 38% (95% CI: -16 to -55%). However, their proportion of unprotected acts changed little (7% reduction, 95% CI: -18 to + 6%). Uninfected women reported little change in number or proportion of unprotected acts over the same time period. CONCLUSIONS: HIV-infected women reduced the number, but not the proportion, of unprotected acts. HIV-negative women did not increase condom use after testing and counselling, but neither did they decrease condom use, suggesting that testing negative was not interpreted as endorsement of risky behaviour.

Total lymphocyte count: not a surrogate marker for risk of death in HIV-infected Ugandan children.

OBJECTIVES: To determine the utility of total lymphocyte count (TLC) in predicting the 12-month mortality in HIV-infected Ugandan children and to correlate TLC and CD4 cell %. DESIGN: This is a retrospective data analysis of clinical and laboratory data collected prospectively on 128 HIV-infected children in the HIV Network for Prevention Trials 012 trial. METHODS: TLC and CD4 cell % measurements were obtained at birth, 14 weeks, and 12, 24, 36, 48, and 60 months of age and assessed with respect to risk of death within 12 months. RESULTS: Median TLC per microliter (CD4 cell %) was 4150 (41%) at birth, 4900 (24%) at 12 months, 4300 (19%) at 24 months, 4150 (19%) at 36 months, 4100 (18%) at 48 months, and 3800 (20%) at 60 months. The highest risk of mortality within 12 months was 34% - 37% at birth and declined to 13%-15% at 24 months regardless of TLC measurement. The correlation between CD4 cell % and TLC was extremely low overall (r = 0.01). CONCLUSIONS: The TLC did not predict a risk of progression to death within 12 months in HIV-infected Ugandan children. Therefore, TLC alone may not be a useful surrogate marker for determining those children at highest risk of death, who require antiretroviral therapy most urgently.

Male circumcision and women's risk of incident chlamydial, gonococcal, and trichomonal infections.

BACKGROUND: Male circumcision (MC) decreases the risk of human immunodeficiency virus (HIV) acquisition in men. We explored associations between MC of the primary sex partner and women's risk of acquisition of chlamydial (Ct), gonococcal (GC), or trichomonal (Tv) infections. METHODS: We analyzed data from a prospective study on hormonal contraception and incident human immunodeficiency virus/sexually transmitted infection (STI) among women from Uganda, Zimbabwe, and Thailand. At enrollment and each follow-up visit, we collected endocervical swabs for polymerase chain reaction identification of Ct and GC; Tv was diagnosed by wet mount. Using Cox proportional hazards models, we compared time to STI acquisition for women according to their partner's MC status. RESULTS: Among 5925 women (2180 from Uganda, 2228 from Zimbabwe, and 1517 from Thailand), 18.6% reported a circumcised primary partner at baseline, 70.8% reported an uncircumcised partner, and 9.7% did not know their partner's circumcision status. During follow-up, 408, 305, and 362 participants had a first incident Ct, GC, or Tv infection, respectively. In multivariate analysis, after controlling for contraceptive method, age, age at coital debut, and country, the adjusted hazard ratio (HR) comparing women with circumcised partners with those with uncircumcised partners for Ct was 1.25 [95% confidence interval (CI) 0.96-1.63]; for GC, adjusted HR 0.99 (95% CI 0.74-1.31); for Tv, adjusted HR 1.05 (95% CI 0.80-1.36), and for the 3 STIs combined, adjusted HR 1.02 (95% CI 0.85-1.21). CONCLUSIONS: MC was not associated with women's risk of acquisition of Ct, GC, or Tv infection in this cohort.

Men's circumcision status and women's risk of HIV acquisition in Zimbabwe and Uganda.

OBJECTIVE: To assess whether male circumcision of the primary sex partner is associated with women's risk of HIV. DESIGN: Data were analyzed from 4417 Ugandan and Zimbabwean women participating in a prospective study of hormonal contraception and HIV acquisition. Most were recruited from family planning clinics; some in Uganda were referred from higher-risk settings such as sexually transmitted disease clinics. METHODS: Using Cox proportional hazards models, time to HIV acquisition was compared for women with circumcised or uncircumcised primary partners. Possible misclassification of male circumcision was assessed using sensitivity analysis. RESULTS: At baseline, 74% reported uncircumcised primary partners, 22% had circumcised partners and 4% had partners of unknown circumcision status. Median follow-up was 23 months, during which 210 women acquired HIV (167, 34, and 9 women whose primary partners were uncircumcised, circumcised, or of unknown circumcision status, respectively). Although unadjusted analyses indicated that women with circumcised partners had lower HIV risk than those with uncircumcised partners, the protective effect disappeared after adjustment for other risk factors [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.69-1.53]. Subgroup analyses suggested a non-significant protective effect of male circumcision on HIV acquisition among Ugandan women referred from higher-risk settings: adjusted HR 0.16 (95% CI, 0.02-1.25) but little effect in Ugandans (HR, 1.33; 95% CI, 0.72-2.47) or Zimbabweans (HR, 1.12; 95% CI, 0.65-1.91) from family planning clinics. CONCLUSIONS: After adjustment, male circumcision was not significantly associated with women's HIV risk. The potential protection offered by male circumcision for women recruited from high-risk settings warrants further investigation.

Knowledge, attitudes and practices on cervical cancer screening among the medical workers of Mulago Hospital, Uganda.

BACKGROUND: Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago national referral and teaching hospital, the biggest hospital in Uganda, have advanced disease. Pap smear screening, on opportunistic rather than systematic basis, is offered free in the gynaecological outpatients clinic and the postnatal/family planning clinics. Medical students in the third and final clerkships are expected to learn the techniques of screening. Objectives of this study were to describe knowledge on cervical cancer, attitudes and practices towards cervical cancer screening among the medical workers of Mulago hospital. METHODS: In a descriptive cross-sectional study, a weighted sample of 310 medical workers including nurses, doctors and final year medical students were interviewed using a self-administered questionnaire. We measured knowledge about cervical cancer: (risk factors, eligibility for screening and screening techniques), attitudes towards cervical cancer screening and practices regarding screening. RESULTS: Response rate was 92% (285). Of these, 93% considered cancer of the cervix a public health problem and knowledge about Pap smear was 83% among respondents. Less than 40% knew risk factors for cervical cancer, eligibility for and screening interval. Of the female respondents, 65% didn't feel susceptible to cervical cancer and 81% had never been screened. Of the male respondents, only 26% had partners who had ever been screened. Only 14% of the final year medical students felt skilled enough to use a vaginal speculum and 87% had never performed a pap smear. CONCLUSION: Despite knowledge of the gravity of cervical cancer and prevention by screening using a Pap smear, attitudes and practices towards screening were negative. The medical workers who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. There is need to explain/understand the cause of these attitudes and practices and identify possible interventions to change them. Medical students leave medical school without adequate skills to be able to effectively screen women for cervical cancer wherever they go to practice. Medical students and nurses training curricula needs review to incorporate practical skills on cervical cancer screening.

Phase I/II trial of HIV-1 hyperimmune globulin for the prevention of HIV-1 vertical transmission in Uganda.

OBJECTIVES: To assess the safety, tolerance, pharmacokinetics, and virologic and immunologic changes associated with the use of Ugandan HIV hyperimmune globulin (HIVIGLOB) in HIV infected pregnant Ugandan women and their infants. DESIGN: A prospective, phase I/II, three-arm dose escalation trial of HIVIGLOB. METHODS: HIVIGLOB was prepared from discarded HIV infected units of blood collected from the National Blood Bank in Kampala. From June 1996 to April 1997, 31 HIV positive pregnant women were enrolled with HIVIGLOB infusions given at 37 weeks gestation and within 16 h of birth for infants. The first 10 mother-infant pairs were infused at a dose of 50 mg/kg, followed by 11 pairs at 200 mg/kg, and 10 pairs at 400 mg/kg. Study participants were followed for 30 months. RESULTS: Thirty-one women and 29 infants were infused with HIVIGLOB. The infusions were safe and well tolerated by the women and their infants at all doses. There were no significant changes in virologic or immunologic parameters after HIVIGLOB infusion. Pharmacokinetic properties of this product were similar to other immune globulin products with a median half-life of 28 days in women and 30 days in infants. CONCLUSION: An HIV immune globulin product derived from HIV infected Ugandan donors is safe, well tolerated, and has pharmacokinetic properties consistent with other immunoglobulin products. Data suggest that a 400 mg/kg dose of HIVIGLOB would be the most appropriate dose for a subsequent efficacy trial of HIVIGLOB for the prevention of mother to child HIV transmission.