Higgins J.A.,University of Wisconsin - Madison |
Gregor L.,University of Wisconsin - Madison |
Mathur S.,Columbia University |
Nakyanjo N.,Rakai Health science Program |
And 2 more authors.
Journal of Sexual Medicine | Year: 2014
Introduction: Although understudied in the context of AIDS, use of withdrawal (coitus interruptus) with or in place of other prevention methods affects exposure to both pregnancy and human immunodeficiency virus (HIV). Aim: We used mixed methods to assess use of withdrawal among 15-24-year-olds in a rural Ugandan setting with considerable HIV prevalence. Methods: We measured withdrawal reporting among (i) sexually active 15-24-year-olds enrolled in a quantitative community survey (n=6,722) and (ii) in-depth qualitative interview participants systematically selected from the latest round of the community survey (N=60). Respondents were asked about family planning and HIV prevention practices, including a direct question about withdrawal in the in-depth interviews. Main Outcome Measures: The main outcome measures were reports of current use of withdrawal on the quantitative survey (general question about family planning methods) and reports of current or recent use withdrawal in qualitative interviews (specific question about withdrawal). Qualitative interviews also probed for factors associated with withdrawal use. Results: Although less than 1% of quantitative survey participants spontaneously named withdrawal as their current family planning method, 48% of qualitative interview respondents reported current or lifetime use of withdrawal. Withdrawal was often used as a pleasurable alternative to condoms, when condoms were not available, and/or as a "placeholder" method before obtaining injectable contraception. A few respondents described using withdrawal to reduce HIV risk. Conclusion: Qualitative findings revealed widespread withdrawal use among young adults in Rakai, mainly as a condom alternative. Thus, withdrawal may shape exposure to both pregnancy and HIV. Future behavioral surveys should assess withdrawal practices directly-and separately from other contraceptives and HIV prevention methods. Further clinical research should further document withdrawal's association with HIV risk. © 2013 International Society for Sexual Medicine.
Reynolds S.J.,National Institute of Allergy and Infectious Diseases |
Reynolds S.J.,Johns Hopkins University |
Makumbi F.,Makerere University |
Newell K.,SAIC |
And 7 more authors.
The Lancet Infectious Diseases | Year: 2012
Background: Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. Methods: We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300-400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log 10 viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov, number NCT00405821. Findings: 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58-0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50 000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43-0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50 000 copies per mL (0·90, 0·54-1·5; p=0·688). No safety issues related to aciclovir treatment were identified. Interpretation: Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50 000 copies per mL or more before initiation of antiretroviral treatment. Funding: National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA). © 2012 Elsevier Ltd.
Chang L.W.,Rakai Health science Program |
Serwadda D.,Makerere University |
Serwadda D.,Rakai Health science Program |
Quinn T.C.,Rakai Health science Program |
And 5 more authors.
The Lancet Infectious Diseases | Year: 2013
The promise of combination HIV prevention-the application of multiple HIV prevention interventions to maximise population-level effects-has never been greater. However, to succeed in achieving significant reductions in HIV incidence, an additional concept needs to be considered: combination implementation. Combination implementation for HIV prevention is the pragmatic, localised application of evidence-based strategies to enable high sustained uptake and quality of interventions for prevention of HIV. In this Review, we explore diverse implementation strategies including HIV testing and counselling models, task shifting, linkage to and retention in care, antiretroviral therapy support, behaviour change, demand creation, and structural interventions, and discusses how they could be used to complement HIV prevention efforts such as medical male circumcision and treatment as prevention. HIV prevention and treatment have arrived at a pivotal moment when combination efforts might result in substantial enough population-level effects to reverse the epidemic and drive towards elimination of HIV. Only through careful consideration of how to implement and operationalise HIV prevention interventions will the HIV community be able to move from clinical trial evidence to population-level effects. © 2013 Elsevier Ltd.
Tobian A.A.R.,Johns Hopkins University |
Kong X.,Johns Hopkins University |
Wawer M.J.,Johns Hopkins University |
Wawer M.J.,Rakai Health science Program |
And 10 more authors.
The Lancet Infectious Diseases | Year: 2011
Background: Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners. Methods: Female partners of HIV-infected men (aged 15-49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878. Findings: 474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86-1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77-1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83-1·12; p=0·61). Interpretation: Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important. Funding: Bill & Melinda Gates Foundation and National Institutes of Health. © 2011 Elsevier Ltd.
Gray R.H.,Johns Hopkins University |
Wawer M.J.,Johns Hopkins University |
Kigozi G.,Rakai Health science Program
Sexually Transmitted Infections | Year: 2013
Three randomised trials demonstrate that voluntary medical male circumcision (MMC) reduces male HIV acquisition by 50-60%, and post-trial surveillance has shown that the effects are long lasting. Scale-up of services has been initiated in 14 high-priority sub-Saharan African countries with high rates of HIV and low prevalence of MMC. However, circumcision coverage in the region remains low. Challenges to MMC rollout include suboptimal demand among higher-risk men, the need to expand access and reduce costs of MMC through personnel task shifting and task sharing, assuring and maintaining a high quality of service provision, and the testing and introduction of non-surgical devices. In addition, early infant male circumcision has not been adequately evaluated in Africa. Here, we describe challenges to implementation and discuss the ongoing and future role of implementation and programme science in addressing such challenges.
Polis C.B.,Office of Population and Reproductive Health Research |
Nakigozi G.F.,Rakai Health science Program |
Nakawooya H.,Rakai Health science Program |
Mondo G.,Rakai Health science Program |
Makumbi F.,Makerere University
Contraception | Year: 2014
Introduction Sayana Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate (DMPA) prefilled in a Uniject injection system, could potentially improve and expand contraceptive injection services, but acceptability of SP is unknown. HIV-positive women need contraception to avoid unintended pregnancy and risk of vertical HIV transmission. We assessed acceptability of SP versus intramuscular DMPA (DMPA-IM) among HIV-positive women and their care providers in Rakai, Uganda. Methods Women were randomized to DMPA-IM or SP at baseline, received the alternate product at 3 months, and chose their preferred method at 6 months. We determined preferences among new and experienced contraceptive injectable users who had tried both types of injection during the trial, and from providers before and after providing both types of injectables to clients. Results Among 357 women randomized, 314 were followed up at 6 months (88%). Although SP caused more skin irritation than DMPA-IM (3.8% vs. 0% at 6 months, p=.03), it was associated with marginally fewer side effects (30.4% vs. 40.4% at 6 months, p=.06). Participants reported high levels of willingness to recommend the DMPA contraception to a friend and satisfaction with the injection received, and these did not differ by injection type. Sixty-four percent of women and 73% of providers preferred SP to DMPA-IM at 6 months; women's preferences did not differ by previous experience with injectable contraception. Conclusions SP is acceptable to HIV-positive women and health care providers in this rural Ugandan population. Implications SP appears to be acceptable to HIV-positive women and their care providers in Rakai, Uganda, and strategies for appropriate rollout of this innovative technology should be explored. © 2014 Elsevier Inc.
Kouyoumdjian F.G.,University of Toronto |
Calzavara L.M.,University of Toronto |
Bondy S.J.,University of Toronto |
O'Campo P.,University of Toronto |
And 6 more authors.
AIDS | Year: 2013
Objectives: To quantify the association between intimate partner violence (IPV) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009. Design and methods: Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009. Longitudinal data analysis was used to estimate the adjusted incidence rate ratio (IRR) of incident HIV associated with IPV in sexually active women aged 15-49 years, using a multivariable Poisson regression model with random effects. The population attributable fraction was calculated. Putative mediators were assessed using Baron and Kenny's criteria and the Sobel-Goodman test. Results: Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 (95% CI1.25-1.94, P = 0.000), compared with women who had never experienced IPV. Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV. The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2% (95% CI 12.5-30.4). There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV. Conclusion: IPV is associated with incident HIV infection in a population-based cohort in Uganda, although the adjusted population attributable fraction is modest. The prevention of IPV should be a public health priority, and could contribute to HIV prevention. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Lutalo T.,Rakai Health science Program |
Musoke R.,Rakai Health science Program |
Kong X.,Johns Hopkins University |
Makumbi F.,Rakai Health science Program |
And 10 more authors.
AIDS | Year: 2013
BACKGROUND:: The risk of HIV associated with hormonal contraceptives is controversial. We assessed hormonal contraceptive use and HIV incidence in HIV-discordant couples in Rakai, Uganda. METHODS:: HIV-discordant couples were retrospectively identified from a cohort between 1999 and 2009. Hormonal contraception included oral contraception, depomedroxyprogesterone acetate (DMPA), and implants (Norplant). Poisson regression estimated adjusted incidence rate ratios (adjIRRs) associated with hormonal contraceptive methods. A case-control subanalysis estimated odds ratios (ORs) of HIV associated with hormonal contraceptive, adjusted for viral load and age. RESULTS:: We identified 190 male HIV-positive/female HIV-negative (M+F-) and 159 male HIV- negative/female HIV-positive (M-F+) couples not using antiretroviral therapy or condoms. Female HIV incidence was 5.8/100 person-years (py) among nonhormonal contraceptive users, 12.0/100 py among oral contraceptive users [adjIRR 2.65, 95% confidence interval (CI) 0.82-8.60], 4.5 among Norplant users (adjIRR: 0.89, 95% CI 0.11-7.10), and 7.5/100 py among DMPA users (adjIRR 1.42, 95% CI 0.60-3.36). Male HIV incidence was 7.4/100 py during nonhormonal contraceptive use, 16.5/100 py during female oral contraceptive use (adjIRR 2.52, 95% CI 0.49-12.95), and 4.9/100 py with DMPA use (adjIRR 0.57, 95% CI 0.19-1.70). The number of female seroconverters was three among oral contraceptive users, one among Norplant users, and seven among DMPA users. Male seroconverters were two during female oral contraceptive use, none with Norplant use, and three with DMPA use. In a nested case-control analysis after adjustment for HIV viral load, the adjOR associated with oral contraceptive use was 1.59 (95% CI 0.32-97.85) for M+F- and 2.11 (95% CI 0.18-25.26) for M-F+ couples. For DMPA use, the adjOR was 1.44 (95% CI 0.46-4.51) for M+F- and 1.40 (95% CI 0.30-6.49) for M-F+ couples. CONCLUSION:: We did not observe significant risk of HIV acquisition or transmission with oral contraceptives or DMPA use in HIV discordant couples, but several point estimates were above 1.0 and statistical power was limited. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Prodger J.L.,University of Toronto |
Kigozi G.,Rakai Health science Program |
Nalugoda F.,Rakai Health science Program |
Galiwango R.,Rakai Health science Program |
And 5 more authors.
Mucosal Immunology | Year: 2012
The foreskin is the main site of heterosexual human immunodeficiency virus (HIV) acquisition in uncircumcised men, but functional data regarding T-cell subsets present at this site are lacking. Foreskin tissue and blood were obtained from Ugandan men undergoing elective adult circumcision. Tissue was treated by mechanical and enzymatic digestion followed by T-cell subset identification and assessment of cytokine production using flow cytometry. Foreskin CD4 T cells were predominantly an effector memory phenotype, and compared with blood they displayed a higher frequency of CCR5 expression (42.0% vs. 9.9%) and interleukin-17 production. There was no difference in T-regulatory cell frequency, but interferon-γ and tumor necrosis factor-α production were increased in foreskin CD8 T cells. These novel techniques demonstrate that the foreskin represents a proinflammatory milieu that is enriched for HIV-susceptible T-cell subsets. Further characterization of foreskin T-cell subsets may help to define the correlates of HIV susceptibility in the foreskin. 2012 Society for Mucosal Immunology.
Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: Secondary analyses of pooled community based data from the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA)
Zaba B.,London School of Hygiene and Tropical Medicine |
Calvert C.,London School of Hygiene and Tropical Medicine |
Marston M.,London School of Hygiene and Tropical Medicine |
Isingo R.,National Institute for Medical Research |
And 10 more authors.
The Lancet | Year: 2013
Background: Model-based estimates of the global proportions of maternal deaths that are in HIV-infected women range from 7% to 21%, and the effects of HIV on the risk of maternal death is highly uncertain. We used longitudinal data from the Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA) network to estimate the excess mortality associated with HIV during pregnancy and the post-partum period in sub-Saharan Africa. Methods: The ALPHA network pooled data gathered between June, 1989 and April, 2012 in six community-based studies in eastern and southern Africa with HIV serological surveillance and verbal-autopsy reporting. Deaths occurring during pregnancy and up to 42 days post partum were defined as pregnancy related. Pregnant or post-partum person-years were calculated for HIV-infected and HIV-uninfected women, and HIV-infected to HIV-uninfected mortality rate ratios and HIV-attributable rates were compared between pregnant or post-partum women and women who were not pregnant or post partum. Findings: 138 074 women aged 15-49 years contributed 636 213 person-years of observation. 49 568 women had 86 963 pregnancies. 6760 of these women died, 235 of them during pregnancy or the post-partum period. Mean prevalence of HIV infection across all person-years in the pooled data was 17·2% (95% CI 17·0-17·3), but 60 of 118 (50·8%) of the women of known HIV status who died during pregnancy or post partum were HIV infected. The mortality rate ratio of HIV-infected to HIV-uninfected women was 20·5 (18·9-22·4) in women who were not pregnant or post partum and 8·2 (5·7-11·8) in pregnant or post-partum women. Excess mortality attributable to HIV was 51·8 (47·8-53·8) per 1000 person-years in women who were not pregnant or post partum and 11·8 (8·4-15·3) per 1000 person-years in pregnant or post-partum women. Interpretation: HIV-infected pregnant or post-partum women had around eight times higher mortality than did their HIV-uninfected counterparts. On the basis of this estimate, we predict that roughly 24% of deaths in pregnant or post-partum women are attributable to HIV in sub-Saharan Africa, suggesting that safe motherhood programmes should pay special attention to the needs of HIV-infected pregnant or post-partum women. © 2013. World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.