Transmitted Antiretroviral Drug Resistance Surveillance among Newly HIV Type 1-Diagnosed Women Attending an Antenatal Clinic in Entebbe, Uganda

Ndembi, Nicaise; Lyagoba, Frederick; Nanteza, Bridget; Kushemererwa, G.; Serwanga, Jennifer; Katongole‐Mbidde, Edward; Grosskurth, Heiner; Kaleebu, Pontiano

doi:10.1089/aid.2007.0317

Cited by 43 publications

(41 citation statements)

References 24 publications

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“…We detected significant variability in the overall prevalence of TDRMs across study populations in our cohort with an increasing prevalence over time, particularly in Lusaka and Zambia, and a high prevalence in Entebbe and Kigali. Based on WHO guidelines for surveillance in areas expanding ARV programs, 16 we observed low (<5%) prevalence at most sites, with medium (5-15%) prevalence in Rwanda in 2007-2009, and, despite small numbers of volunteers, a higher than previously reported 14 prevalence in Entebbe (>15%) and more recently in Zambia (>15%). The reported prevalence of TDRMs in industrialized countries has ranged from 8% to 27% and has been shown to be increasing over time, with the introduction of ARV therapy.…”

Section: Discussionmentioning

confidence: 48%

“…Our volunteers in Entebbe represent different source populations, as 9 were male, 18 were identified as incident infections from the centersupported VCT clinic, 8 were participants in our HIVdiscordant couples cohort ongoing at the same time, and all volunteers were recently infected when diagnosed; the women 14 were diagnosed at an antenatal clinic, and it is not clear when they became HIV infected. Other African populations have tended to reveal modest to no TDRMs.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] This has led to recommendations for drug resistance testing as soon as HIV-1 infection is detected to guide first-line drug choices. 7,8 Published reports have suggested that TDRMs in ARV-naive Africans has been uncommon [9][10][11][12][13][14] ; however, much higher rates of drug resistance in Africa have been reported among patients with a history of ARV use. 15 Recently, the WHO has published recommendations for surveillance in countries scaling up ARV therapy programs, 16,17 and results from Africa using these recommendations have shown a low (<5%) prevalence of TDRMs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa

Price

Wallis

Lakhi

et al. 2011

AIDS Research and Human Retroviruses

104

111

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To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIVinfected African volunteers, we sequenced HIV ( pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia ( p ¼ 0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa

Price

Wallis

Lakhi

et al. 2011

AIDS Research and Human Retroviruses

104

111

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“…8,9 Initial surveys of TDR in sub-Saharan Africa during early ARV scale-up have shown a prevalence of below 5%. 8,[10][11][12][13][14] However, recent surveys suggest that TDR increases as these countries scale-up antiretroviral treatment (ART) access. 15 There are no data on TDR from fishing communities in Uganda, and given the higher prevalence and incidence it is important to determine the levels of TDR in these highly mobile populations.…”

Section: Introductionmentioning

confidence: 99%

Short Communication: HIV Type 1 Transmitted Drug Resistance and Evidence of Transmission Clusters Among Recently Infected Antiretroviral-Naive Individuals from Ugandan Fishing Communities of Lake Victoria

Nazziwa

Njai

Ndembi

et al. 2013

AIDS Research and Human Retroviruses

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Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene ( protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/ 47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.

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“…Indeed, in the United States and Europe, it is estimated that 10% to 20% of new infections are caused by HIV-1 strains harboring resistance to at least one of the three main types of ARV drugs: entry/fusion inhibitors, RTIs, or protease inhibitors (6,11,12,30,46,58,70,77). Although levels of RTI resistance in the developing world are not fully characterized (26,48,49,63,72), they are likely to increase with the scale-up of ARV therapy. The development of combination ARV rectal microbicides might provide an important defense against rectal transmission of resistant strains of HIV-1 in regions where treatment of chronic HIV infection has resulted in the emergence of ARV resistance.…”

mentioning

confidence: 99%

Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides

Herrera

Cranage

McGowan

et al. 2009

Antimicrob Agents Chemother

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We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI-and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.

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Transmitted Antiretroviral Drug Resistance Surveillance among Newly HIV Type 1-Diagnosed Women Attending an Antenatal Clinic in Entebbe, Uganda

Cited by 43 publications

References 24 publications

Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa

Transmitted HIV Type 1 Drug Resistance Among Individuals with Recent HIV Infection in East and Southern Africa

Short Communication: HIV Type 1 Transmitted Drug Resistance and Evidence of Transmission Clusters Among Recently Infected Antiretroviral-Naive Individuals from Ugandan Fishing Communities of Lake Victoria

Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides

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