Rwanda Zambia HIV Research Group

La Grange, GA, United States

Rwanda Zambia HIV Research Group

La Grange, GA, United States
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Mugo N.R.,University of Nairobi | Mugo N.R.,University of Washington | Heffron R.,University of Washington | Donnell D.,Fred Hutchinson Cancer Research Center | And 10 more authors.
AIDS | Year: 2011

BACKGROUND: Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1-infected women to male partners. METHODS: In a prospective study of African HIV-1-serodiscordant couples, we evaluated the relationship between pregnancy and the risk of HIV-1 acquisition among women and HIV-1 transmission from women to men. RESULTS: Three thousand three hundred and twenty-one HIV-1-serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100person-years during pregnant and nonpregnant periods [hazard ratio 2.34, 95% confidence interval (CI) 1.33-4.09]. This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted hazard ratio 1.71, 95% CI 0.93-3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100person-years when their partners were pregnant versus not pregnant (hazard ratio 2.31, 95% CI 1.22-4.39). This effect was not attenuated in adjusted analysis (adjusted hazard ratio 2.47, 95% CI 1.26-4.85). CONCLUSION: HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show that pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. © 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Haddad L.,Rwanda Zambia HIV Research Group | Haddad L.,Emory University | Wall K.M.,Rwanda Zambia HIV Research Group | Wall K.M.,Emory University | And 11 more authors.
AIDS | Year: 2013

OBJECTIVE:: To describe predictors of contraceptive method discontinuation and switching behaviours among HIV-positive couples receiving couples' voluntary HIV counselling and testing services in Lusaka, Zambia. DESIGN:: Couples were randomized in a factorial design to two-family planning educational intervention videos, received comprehensive family planning services and were assessed every 3 months for contraceptive initiation, discontinuation and switching. METHODS:: We modelled factors associated with contraceptive method upgrading and downgrading via multivariate Andersen-Gill models. RESULTS:: Most women continued the initial method selected after randomization. The highest rates of discontinuation/switching were observed for injectable contraceptive and intrauterine device users. Time to discontinuing the more effective contraceptive methods or downgrading to oral contraceptives or condoms was associated with the womenÊs younger age, desire for more children within the next year, heavy menstrual bleeding, bleeding between periods and cystitis/dysuria. Health concerns among women about contraceptive implants and male partners not wanting more children were associated with upgrading from oral contraceptives or condoms. HIV status of the woman or the couple was not predictive of switching or stopping. CONCLUSION:: We found complicated patterns of contraceptive use. The predictors of contraception switching indicate that interventions targeted to younger couples that address common contraception-related misconceptions could improve effective family planning utilization. We recommend these findings be used to increase the uptake and continuation of contraception, especially long-acting reversible contraceptive (LARC) methods, and that fertility goal based, LARC-focused family planning be offered as an integral part of HIV prevention services. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Chin C.D.,Columbia University | Cheung Y.K.,Columbia University | Laksanasopin T.,Columbia University | Modena M.M.,Columbia University | And 16 more authors.
Clinical Chemistry | Year: 2013

Background: Collection of epidemiological data and care of patients are hampered by lack of access to laboratory diagnostic equipment and patients' health records in resource-limited settings. We engineered a low-cost mobile device that combines cell-phone and satellite communication technologies with fluid miniaturization techniques for performing all essential ELISA functions. Methods: We assessed the device's ability to perform HIV serodiagnostic testing in Rwanda and synchronize results in real time with electronic health records. We tested serum, plasma, and whole blood samples collected in Rwanda and on a commercially available sample panel made of mixed antibody titers. Results: HIV testing on 167 Rwandan patients evaluated for HIV, viral hepatitis, and sexually transmitted infections yielded diagnostic sensitivity and specificity of 100% and 99%, respectively. Testing on 40 Rwandan whole-blood samples-using 1 μL of sample per patient-resulted in diagnostic sensitivity and specificity of 100% and 100%. The mobile device also successfully transmitted all whole-blood test results from a Rwandan clinic to a medical records database stored on the cloud. For all samples in the commercial panel, the device produced results in agreement with a leading ELISA test, including detection of weakly positive samples that were missed by existing rapid tests. The device operated autonomously with minimal user input, produced each result 10 times faster than benchtop ELISA, and consumed as little power as a mobile phone. Conclusions: A low-cost mobile device can perform a blood-based HIV serodiagnostic test with laboratorylevel accuracy and real-time synchronization of patient health record data. Copyright © 2012 American Association for Clinical Chemistry.


PubMed | University of KwaZulu - Natal, La Jolla Institute for Allergy and Immunology, Emory University, British Columbia Center for Excellence in and 9 more.
Type: Journal Article | Journal: Nature medicine | Year: 2016

Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits holes in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.


Baeten J.M.,University of Washington | Donnell D.,Fred Hutchinson Cancer Research Center | Kapiga S.H.,London School of Hygiene and Tropical Medicine | Kapiga S.H.,Kilimanjaro Christian Medical Center | And 6 more authors.
AIDS | Year: 2010

Objective: Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision. DESIGN/Methods: Data collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used. Results: A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). Conclusion: Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, we observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | University of Witwatersrand, University of Washington, Fred Hutchinson Cancer Research Center, Kenya Medical Research Institute and 7 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis.We examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.Transmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).Condoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.


Chin C.D.,Columbia University | Laksanasopin T.,Columbia University | Cheung Y.K.,Columbia University | Steinmiller D.,Claros Diagnostics | And 15 more authors.
Nature Medicine | Year: 2011

One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 Î 1/4l of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings. © 2011 Nature America, Inc. All rights reserved.


Kelley A.L.,Rwanda Zambia HIV Research Group | Karita E.,Rwanda Zambia HIV Research Group | Sullivan P.S.,Emory University | Katangulia F.,Scientific Monitoring, Inc. | And 8 more authors.
PLoS ONE | Year: 2011

Background: Most incident HIV infections in sub-Saharan Africa occur between cohabiting, discordant, heterosexual couples. Though couples' voluntary HIV counseling and testing (CVCT) is an effective, well-studied intervention in Africa, <1% of couples have been jointly tested. Methods: We conducted cross-sectional household surveys in Kigali, Rwanda (n = 600) and Lusaka, Zambia (n = 603) to ascertain knowledge, perceptions, and barriers to use of CVCT. Results: Compared to Lusaka, Kigali respondents were significantly more aware of HIV testing sites (79% vs. 56%); had greater knowledge of HIV serodiscordance between couples (83% vs. 43%); believed CVCT is good (96% vs. 72%); and were willing to test jointly (91% vs. 47%). Stigma, fear of partner reaction, and distance/cost/logistics were CVCT barriers. Conclusions: Though most respondents had positive attitudes toward CVCT, the majority were unaware that serodiscordance between cohabiting couples is possible. Future messages should target gaps in knowledge about serodiscordance, provide logistical information about CVCT services, and aim to reduce stigma and fear. © 2011 Kelley et al.


Lambdin B.H.,Pangaea Global AIDS Foundation | Kanweka W.,Us Agency For International Development | Inambao M.,Zambia Emory HIV Research Project | Mwananyanda L.,mothers2mothers | And 6 more authors.
Health Affairs | Year: 2011

Couples in sub-Saharan Africa are the largest group in the world at risk for HIV infection. Couples counseling and testing programs have been shown to reduce HIV transmission, but such programs remain rare in Africa. Before couples counseling and testing can become the norm, it is essential to increase demand for the services. We evaluated the effectiveness of several promotional strategies during a two-year program in Kitwe and Ndola, Zambia. The program attracted more than 7,600 couples through the use of radio broadcasts, billboards, and other strategies. The most effective recruiting technique was the use of local residents trained as "influence agents" to reach out to friends, neighbors, and others in their sphere of influence. © 2011 Project HOPE-The People-to-People Health Foundation, Inc.


Kraft C.S.,Emory University | Basu D.,Emory University | Hawkins P.A.,Emory University | Hraber P.T.,Los Alamos National Laboratory | And 10 more authors.
Retrovirology | Year: 2012

Background: HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples.Results: Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection.Conclusions: In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals. © 2012 Kraft et al; licensee BioMed Central Ltd.

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